JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-014-0190-1 (2014)

Reviewer's report
Title:Anti-Outer membrane protein C and anti-glycoprotein 2 antibodies in
inflammatory bowel disease and their association with complicated forms of
Crohn's disease
Version:1Date:10 September 2014
Reviewer: Federico Biagi
Reviewer's report:
In this paper Kohoutova et al. studied anti-Outer membrane protein C and
anti-glycoprotein 2 antibodies in inflammatory bowel disease and their
association with complicated forms of Crohn´s disease. There are some
concerns:
1. The authors state that this is not a novel study but it is confirmatory of previous
ones. However, the present study is difficult to read. The result section needs to
be simplified and better explained.
2. Also the tables are rather chaotic. For example, reading the text, I assumed
that tables 2 and 3 presented clinical data on the patients (n° of males and
females, age at diagnosis, age at testing, etc) while they present antibody
results. The antibodies results could be all presented in these tables, including
statistical significance, and omitted from the main results section.
3. The authors write that this is a prospective study performed between 2010 and
2012. Since all the experiments were performed with ELISA techniques, I think
they collected the serum samples, froze and stored them to be tested all together
with the ELISA kits. If this should be the case, I am not sure that this is a
prospective study.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/s12876-014-0223-9 (2014)

Reviewer's report
Title:The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated
with peptic ulcer and gastric cancer in Mexican population
Version:3Date:8 October 2014
Reviewer: Christophe BURUCOA
Reviewer's report:
The manuscript of Beltran-Anaya et al. is a single-center descriptive study
seeking in 499 mexican patients the presence of H. pylori infection and the
presence and motifs of EPIYA CagA. The search for the infection and
characterization of virulence genes is performed using PCR technology on
biopsies directly, without isolation of the bacterium in culture. They report a high
prevalence of CagA in the Mexican population. They show the statistical
relationship between the number of patterns Epiya-C and ulcerous and
cancerous diseases. The strength of this work is the large number of patients
studied. The results presented are not very original, numerous articles have
allready been published in numerous studies in the world, in South America but
never in South Mexico. The manuscript is well written, clear. Some
improvements are proposed:
• Give the dates of the patient inclusion
• Describe the analysis of electrophoretic profiles for defining patterns and
number Epiya
• Line 320 de change the
• Line 523 26 the number not in bold
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 interest
Review for 10.1186/s12876-014-0223-9 (2014)

Reviewer's report
Title:The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated
with peptic ulcer and gastric cancer in Mexican population
Version:3Date:14 October 2014
Reviewer: Robert Raffaniello
Reviewer's report:
This study examines the relationship between H pylori and GI disorders in
Mexican patients with gastric pathologies. The prevalence of the CagA gene and
the EPIYA motif patterns of this virulence factor are also examined. The sample
size is adequate and the paper is well written. The results are presented well and
discussed intelligently. The findings are interesting and important. However, I
have a couple of issues regarding the study:
Major issues:
I am not sure why the authors chose to determine CagA types (ABC, ABCC, etc)
by PCR as opposed to sequencing the C-terminal of all 214 CagA+ samples.
This may actually be less expensive than all the PCR rxs involved. Instead, only
20 random samples were sequenced. With the complete sequence data, there
would be little ambiguity regarding the EPIYA arrangements, CRIPA sequences
and EPIYA-B polymorphisms. A more detailed and meaningful analysis would be
obtained.
My other question involves the histology samples. As mentioned in methods,
samples were taken for histology, but the results are not presented. If the
samples were examined for precancerous changes (atrophy, metaplasia),
inflammatory intensity, anaplasia, etc., this data could be related to Hp infection
and the presence of CagA. Do the authors intend to present this as a separate
study?
Minor issues (suggestions):
Line 280 It may be better to say “on the other hand.” (not by other hand)
Lines 306-308 should be reworded to be more clear.
Line 320-‘de cases’??
Line 350-change ‘likely’ to ‘possible’.
Figure 1 X-axis of top two graphs should be % H pylori positive % CagA positive.
Figure 2 It is Not clear what primers were used in these experiments. It is not
stated in legend.
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/s12876-014-0223-9 (2014)

Reviewer's report
Title:The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated
with peptic ulcer and gastric cancer in Mexican population
Version:6Date:12 December 2014
Reviewer: Dionyssios Sgouras
Reviewer's report:
In reviewing the point-to-point rebuttal, I feel that the authors have made a very
honest attempt to address sufficiently well, all the points I raised, whether they
were major compulsory, minor essential or discretionary.
Adequate answers to major compulsory points have been incorporated in the
revised document. The minor essential points have been sufficiently addressed
I have no further comments
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/s12876-014-0221-y (2014)

Reviewer's report
Title:Mutational Profiles of Different Macroscopic Subtypes of Colorectal
Adenoma Reveal Distinct Pathogenetic Roles for KRAS, BRAF and PIK3CA
Version:3Date:10 November 2014
Reviewer: Yutaka Saito
Reviewer's report:
I read this paper with interest. This is an important paper, however, there is minor
points to be revised.
Please describe the reason why k-ras and b-raf mutation were 0% in 24
depressed type cancers in detailed. It is a little bit strange.
Please refer to the paper.
Distinct molecular features of different macroscopic subtypes of colorectal
neoplasms.
Konda K, Konishi K, Yamochi T, Ito YM, Nozawa H, Tojo M, Shinmura K, Kogo
M, Katagiri A, Kubota Y, Muramoto T, Yano Y, Kobayashi Y, Kihara T, Tagawa T,
Makino R, Takimoto M, Imawari M, Yoshida H.
PLoS One. 2014 Aug 5;9(8):e103822
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests' below
Review for 10.1186/s12876-014-0221-y (2014)

Reviewer's report
Title:Mutational Profiles of Different Macroscopic Subtypes of Colorectal
Adenoma Reveal Distinct Pathogenetic Roles for KRAS, BRAF and PIK3CA
Version:3Date:10 November 2014
Reviewer: Takahisa Matsuda
Reviewer's report:
This is the single center prospective study to elucidate the frequency of KRAS
mutation and BRAF mutation in polypoid, flat and depressed colorectal
neoplasms and compare these morphological counterparts each other. The
authors hold a body of data which is valuable. A few changes and additional
description would improve the overall message. I have only a few comments.
1. The authors should quote this article. Kaji E, Kato J, Suzuki H, et al, Analysis
of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the
colorectum. J Gastroenterol Hepatol 2011.
2. I suppose that the number of subjects is limited, therefore, it seems to be
difficult to discuss with regard to the frequency of KRAS mutation based on the
lesions’ location. This is a limitation of this prospective study. The authors should
discuss about this issue or describe as one of limitation in the discussion section.
3. Table 2: Please revise the term from “RIK3CA” to “PIK3CA”.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
None
Review for 10.1186/s12876-014-0225-7 (2014)

Reviewer's report
Title:Clinical value of wireless pH-monitoring of gastroesophageal reflux in
children before and after proton pump inhibitors
Version:2Date:21 September 2014
Reviewer: Manuele Furnari
Reviewer's report:
I read with interest the manuscript by Bostrõm et al.
They evaluated the potential benefit of using Bravo system for GERD evaluation
in children. The authors reported Bravo system as safe and tolerable in children
and allows to obtain further information about PPI response due to the availabity
of extra 24h recording.
The manuscript is overall well written, states clearly the aim and provide all the
information the reader may need in order to reproduce and evaluate the variables
investigated.
However, there are a couple of revisions the authors should deal with.
Minor:
1 in the abstract children is mistyped (introduction).
Major:
2 in the results sections the authors reported that only 26 pota had microscopic
esophagitis. I believe this is extremely low incidente. Furthermore, it is markedly
allarming that 26 patients had macroscopic signs of esophagitis and normal
histology.
about Several studies (in adults) reported incidence of ME even among subject
with normal EGDs and MII-pH, and 90-70% of ME among subjects with
esophagitis or proven NERD.
The authors should discussed it and provide reasonable explanation of their
results.
One might be hipothesized that there was not sufficient training among the
pathogists or, more probable, a tendency to over-estimate the endoscopic
findings.
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:
None
Review for 10.1186/s12876-014-0216-8 (2014)

Reviewer's report
Title:Early Life Environment and Natural History of Inflammatory Bowel Diseases
Version:3Date:23 October 2014
Reviewer: Whitney Tang
Reviewer's report:
Minor Essential Revisions
1. Method: There is no sample size justification. Will the non-significant
association between exposures and surgery in UC due to under power of small
sample size?
2. Results: There is a category of “unsure” in the questionnaire. Are they
excluded from the analysis? What is the sample size included in the multivariate
regression models and mutually adjusted model?
3. Results: Although studies showed conflicting result, exposure to antibiotics is
also a factor of interest as an important environmental factors associated with
IBD pathogenesis. There is question about antibiotics included in the
questionnaire. Was the association between exposure to antibiotics and disease
outcome analyzed?
4. Table 1: Characteristics of study population can be separated into UC and CD
since they were analyzed separately, and only factors associated with CD
showed significant result.
5. Typo in line 166: 95% CI
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/s12876-014-0216-8 (2014)

Reviewer's report
Title:Early Life Environment and Natural History of Inflammatory Bowel Diseases
Version:3Date:29 October 2014
Reviewer: Sunny Hei Wong
Reviewer's report:
This study addresses an important question on the effect of early life exposure
on the course of IBD. The study has a decent study design and methodology,
and the statistical methods are valid. This paper is potentially publishable if the
following questions are addressed.
Minor essential revisions as follows
1. The authors have included several factors like the age of diagnosis, disease
location and perianal involvement as potential confounding factors. Have they
included other known adverse factors, such as steroid use at first presentation,
as a potential confounding factor?
2. The chance of surgery is affected by the duration of disease. This is very
major confounding factor. While the authors have rightly put that in the
regression model, can they provide more details on this factor? What are the the
mean durations and the SD of the two groups (surgery vs no surgery), and are
there significant differences between the groups?
3. The first letter of the italicized bacteria names should be capitalized in lines
208-209.
4. Please provide evidence or reference for the statement "early life exposure
may have greater and more sustained effects on the gut microbiome than
exposures later on in adult life" (line 226-227)
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/s12876-014-0222-x (2014)

Reviewer's report
Title:Liver ENPP1 Protein Increases with Remission of Type 2 Diabetes after
Gastric Bypass Surgery
Version:2Date:9 November 2014
Reviewer: Katrina L Purcell
Reviewer's report:
Minor essential revisions
Information regarding the medication participants were taking pre and
post-surgery is important. This is because, Stefanovic et al. 2004 reported that
ectonucleotide pyrophosphatase phosphodiesterase 1 is increased in
lymphocytes from T2D patients, and this increase was reversed by metformin
treatment. The same group has also reported that ectonucleotide
pyrophosphatase phosphodiesterase 1 is elevated in insulin-resistant uremic
patients, and this elevated ectonucleotide pyrophosphatase phosphodiesterase 1
is reversed by erythropoietin therapy.
Stefanovic V, Antic S 2004 Plasma cell membrane glycoprotein 1 (PC-1): a
marker of insulin resistance in obesity, uremia and diabetes mellitus. Clin Lab
50:271–278
Stefanovic V, Antic S, Mitic-Zlatkovic M, Vlahovic P Reversal of increased
lymphocyte PC-1 activity in patients with type 2 diabetes treated with metformin.
Diabetes Metab Res Rev 1999 15:400–404
What were the reasons for repeat biopsy?
Is the promoter of ENPP1 gene glucose responsive?
Discretionary revisions:
It would be helpful to the reader to specify what your primary and secondary aims
of the paper are.
It would be helpful to define the dates defining the recruitment period.
Figures are neatly presented. Table 1 and 2 could be put into one table. Flow
diagram of study participants would be helpful. Headings of tables should be
consistent e.g. before RYGB mentioned in table 1 and before first liver biopsy
mentioned in table 2 and individuals at RYGB (initial liver biopsy) mentioned in
table 3.
Possible conclusion could be ‘this is natures way of making more insulin
available to suppress hyperglycaemia’.
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/s12876-014-0220-z (2014)

Reviewer's report
Title:A risk assessment instrument to identify ulcerative colitis patients at high
risk of non-adherence to aminosalicylate medication based on the Health Belief
Model: a cross-sectional study
Version:2Date:30 September 2014
Reviewer: Klaudia Farkas
Reviewer's report:
This is a well organized study by Kawakami et al performed on large IBD
population. With the use of a multicenter cross-sectional study the authors
developed an assessment instrument to identify patients with ulcerative colitis at
high risk of non-adherence to aminosalicylates and to assess factors of
non-adherence based on the Health Belief Model (HBM).
Discretionary Revisions: Was the correlation between non-adherence and the
current disease activity and duration of UC examine? These information would
be interesting to know.
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:
No conflict of interest.
Review for 10.1186/s12876-014-0220-z (2014)

Reviewer's report
Title:A risk assessment instrument to identify ulcerative colitis patients at high
risk of non-adherence to aminosalicylate medication based on the Health Belief
Model: a cross-sectional study
Version:2Date:30 September 2014
Reviewer: Fernando Gomollón García
Reviewer's report:
After a careful review of the paper, I have to congratulate authors because the
report is very clear, the work is very well designed, and you make a considerable
contribution on the literature on adherence in UC
My only point is that (although you clearly recognize it in the paper) the
instrument you design should be validated in:
a) A prospective trial in your population with previous definition of activity etc
b) One or several trials in different populations
The other minimal problem is that a reference standard method (Morisky scale,
for instance) could have been useful to compare with other trials; although I
acknowledge that the reference method used in your work seems to be valid, as
shown in another small group.
Thanks for your excellent work
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/s12876-014-0210-1 (2014)

Reviewer's report
Title:Management of Upper Gastrointestinal Bleeding in a Nigerian tertiary health
facility
Version:2Date:27 August 2014
Reviewer: Yi-Chun Chiu
Reviewer's report:
This manuscript"Management of Upper Gastrointestinal Bleeding in a Nigerian
tertiary health facility" reflected the clinical condition of a economic resource poor
country. The authors made a great effort to provide a better endoscopic therapy
in this country. However, the results in this study did not possess sufficient
interest for publication in a scientific journal.
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.
Review for 10.1186/s12876-014-0210-1 (2014)

Reviewer's report
Title:Management of Upper Gastrointestinal Bleeding in a Nigerian tertiary health
facility
Version:2Date:9 September 2014
Reviewer: Wei-Chen Tai
Reviewer's report:
This is an article dealing with “Management of Upper GI bleeding in a Nigerian
tertiary health facility”. This article didn’t give us new information about the
treatment of upper GI bleeding, however, we can understand the medical
circumstance in Nigeria.
There are certain flaws and queries that should be addressed.
Major Compulsory Revisions (1)~(5)
(1)The authors are suggested to change the title to “Management of Upper GI
bleeding in a Nigerian tertiary health resource-poor facility”
(2)The authors should state the limitations of this study in the discussion section.
(3)The authors should strengthen the article and focus on how the situation could
be improved and the potential problem that could allow them to do better in future
(4)The manuscript needs extensive English editing.
(5)Figure 2 is not needed.
Minor Essential Revisions (1)~(7)
(1) Page 6, Line 20
20 multiple source were identified
-> multiple sources were identified
(2) Page 7, Line 5
5 Nasogastric tube was passed to monitor continuous bleeding.
->Nasogastric tube was inserted to monitor continuous bleeding.
(3) Page 7, Line 14
14 variceal bleeding had injection sclerotherapy or rubber band ligation
-> variceal bleeding had received injection sclerotherapy or rubber band ligation
(4) Page 8, Line 1-4
1 the FORREST Classification as follows: FI – Active bleeding (FIa – arterial,
spurting
2 hemorrhage, FIb – oozing hemorrhage), FII – Stigmata of recent haemorrhage
(FIIa – Visible
3 vessel, FIIb – Adherent clot, FIIc –Dark base - haematin covered lesion, FIII
–Lesions
4 without active bleeding.14
-> May cutout the description of the FORREST Classification.
(5) Page 9, Line 7
7 were females with a male to female ratio of 2.6:1. Their ages ranged from 3 to
100 years with
-> The age range of the patients was 3 to 100 years with
(6) Page 10, Line 19
19 therapy. Only 21 (40.4%) patients had variceal band ligation (Figure 2).
-> Figure of variceal band ligation (Figure 2.) might be removed.
(7) Page 27, Table 1
-> In Table 1, there were four patients with gastric polyp as endoscopic diagnosis
of UGIB, one patient with vascular bleeding, would you please give us more
information about the bleeding sources of these four patients.
-> In Table 1, there were eight patients had GIST, does it result in bleeding or
just incidental finding?
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/s12876-014-0210-1 (2014)

Reviewer's report
Title:Management of Upper Gastrointestinal Bleeding in a Nigerian tertiary health
facility
Version:2Date:20 September 2014
Reviewer: Sung-shuo Kao
Reviewer's report:
My comments
1) Since duodenal ulcer is the majority cause of upper GI bleeding in this study,
the prevalence of Helicobacter pylori infection and the percentage of patients
using NSAID/anti-platelet drugs are better recorded. If HP status was not
checked in some patients, it deserved to be discussed in the limitation.
2) In page 10 and 11, the author demonstrated the benefits of endoscopic
therapy for variceal bleeding. In page 17, the conclusion said that #Endoscopic
therapy in resource poor setting like Nigeria could be life-saving.# This is partially
true according to current presentation. For the conclusion that endoscopic
therapy is life-saving, it's better for the author to compare the mortality and
rebleeding rate between groups who received endoscopic therapy and groups
who did not.
3) In page 11, the author reported the effectiveness of endoscopic therapy is
90.5%, and no rebleeding was found in patients with ulcer bleeding. I am
interested in the rebleeding rate in patients who should but did not receive
endoscopic therapy. Is there any significance between these two groups? If so,
what is the rebleeding rate in untreated group?
4) The rate of gastritis-related bleeding is higher than that of gastric ulcer
bleeding in this study. It would be nice to see the reason why gastritis-related GI
bleeding is high in Southern Nigeria.
5) The author has done many subgroup comparison and analysis. This is really a
good chance to see the difference between treated and untreated patients. To
clarify the analytic data, I suggested the author to set a table demonstrating
mortality, rebleeding, blood transfusion units, and hospital stay in treated and
untreated groups.
Specific comments:
1) P.4 line 6. #will died of# is better corrected as #will die of#
2) P.7 line 18. #Injection sclerotherapy# is better corrected as #injection therapy#
3) P.13 line 15. #Upper GI endoscopy remain# is better corrected as #Upper GI
endoscopy remains#
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/s12876-014-0218-6 (2014)

Reviewer's report
Title:HBV DNA level, not liver stiffness value, could predict significant liver
fibrosis in HBeAg negative chronic hepatitis B patients with liver biopsy indication
as AASLD and APASL guidelines
Version:2Date:8 October 2014
Reviewer: Cosmas Rinaldi Lesmana
Reviewer's report:
Major Concerns:
1. The sample size is small.
2. Could contain selection bias as the authors highlight in the discussion.
3. It was not clear enough the age selection criteria based.
4. There is no clear explanation in the discussion about more fibrosis in the
younger age.
Minor Concern:
The language need to be polished.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
No conflict of interest.
Review for 10.1186/s12876-014-0218-6 (2014)

Reviewer's report
Title:HBV DNA level, not liver stiffness value, could predict significant liver
fibrosis in HBeAg negative chronic hepatitis B patients with liver biopsy indication
as AASLD and APASL guidelines
Version:2Date:18 October 2014
Reviewer: Vincent Wong
Reviewer's report:
This is a well-written article on a clinically relevant topic. Current guidelines
suggest liver biopsy in different patient groups. However, due to the large
number of patients in endemic areas, this is often unrealistic. Although the
sample size of this study is small, this point has been adequately addressed in
the discussion.
Specific points:
1. How many pathologists were involved in the interpretation of liver histology?
2. Please quality indicators of the liver biopsy samples such as the length of liver
samples and the number of portal tracts.
3. Please report the quality of liver stiffness measurements.
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 have served as a speaker for Echosens.
Review for 10.1186/s12876-014-0217-7 (2014)

Reviewer's report
Title:Prospective cross-sectional study on faecal immunochemical tests: sex
specific cut-off values to obtain equal sensitivity for colorectal cancer?
Version:5Date:25 August 2014
Reviewer: Harkirat Singh
Reviewer's report:
Major Revisions:
1. Please provide the sensitivity and specificity data of FIT in symptomatic vs
screening/surveillance groups.
2. In the last para of discussion
"However, in a recent comparison of CRC cases from the current study cohort
with CRC cases from a screening population, similar FIT
324 results were found.[21] "
Its unclear how this statement fits here with this citation.
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/s12876-014-0213-y (2014)

Reviewer's report
Title:Gallstones associated with non-alcoholic fatty liver disease in female rather
than male: a longitudinal cohort study
Version:1Date:12 February 2014
Reviewer: Frank Tacke
Reviewer's report:
This is an interesting longitudinal cohort study aiming at elucidating the
relationship between NAFLD and gallstones.
- As the authors point out themselves, the association between NAFLD and
gallstones is well established from several cohorts (from different parts of the
world), which limits the novelty of the current analysis.
- Language and grammar needs some thorough editing, ideally by a native
speaker.
- A major difficulty in interpreting the data is the validity of the ultrasound exam.
Did all subject undergo abdominal ultrasound at the time-point of inclusion into
the study? How was the quality of the ultrasound validated? Did an independent
observer confirm diagnosis of hepatic steatosis? How was alcohol intake
quantified? In how many individuals was NAFLD assumed (diagnosed) without
proper exclusion of other causes (HBV, HCV, alcohol etc.)?
- A major limitation is that ALT and AST levels are not reported. This basically
precludes to accurately stage NAFLD (into either ‘benign steatosis’, NASH,
fibrosis, cirrhosis or HCC).
- The authors not only need to assess the association between NAFLD and
gallstones, but also with its disease-specific complications. That means, does the
presence of gallstones predispose to cirrhosis or HCC? Does the presence of
NAFLD predispose to symptomatic cholecystolithiasis, cholecystitis or
empyema?
- As the authors point out, gallstones and NAFLD share the same risk factors.
Table 1 presents possible confounding factors. However, the factor NAFLD
(yes/no) needs to be compared to ‘cardiovascular disease’, ‘diabetes’, ‘arterial
hypertension’ etc. Is NAFLD then still an independent predictor of gallstones?
- Was the use of medication (e.g., statins, aspirin, ace-inhibitors etc.) monitored?
How did distinct drugs or classes of drugs impact NAFLD and/or gallstones?
- NAFLD is apparently not a risk factor for gallstones in male. This needs to be
properly discussed. On the other hand, the reader is left wondering whether the
proposed causal relationship between NAFLD and gallstones is really true (why
should this differ between male and female subjects?).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
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/s12876-014-0213-y (2014)

Reviewer's report
Title:Gallstones associated with non-alcoholic fatty liver disease in female rather
than male: a longitudinal cohort study
Version:1Date:30 July 2014
Reviewer: Monica Acalovschi
Reviewer's report:
Comments to the Authors
The study Gallstones associated with non-alcoholic fatty liver disease in female
rather than male: a longitudinal cohort study by Jia Liu et al is an interesting
study performed on a large population aiming to confirm the increased incidence
of gallstones in NAFLD patients, an association documented mainly in
cross-sectional studies. The authors performed a longitudinal study of patients
with NAFLD. Following-up for 6 years a large group of subjects with and without
NAFLD, the authors found an incidence of gallstones in NAFLD patients of 12,73
per 1,000 persons-year, significantly higher than in non-NAFLD subjects.
Analyzing some of the known risk factors in subjects who developed gallstones,
the authors demonstrate that NAFLD is an independent risk factor for gallstone
disease.
Major comments:
1. The study population was recruited among individuals from one city in China
who attended a health screening and therefore may not represent the entire
community. I suggest adding in the title…. a longitudinal cohort study in a
Chinese urban population
2. I suggest introducing supplementary tables 1 and 2 as regular tables in the
text, so that readers may easier follow the frame of the study.
3. The number of subjects followed-up for 6 years was much lower than of those
who were examined 2 or 3 years due to different moments of enrolment starting
with 2005. How could this have influenced the study results?
4. Incidence of gallstones did not increase during follow-up after NAFLD
diagnosis, suggesting that age is not a predisposing factor for gallstones in
NAFLD patients. This is in contrast with studies in different populations and in
NAFLD patients (Fracanzani et al, 2012, Loria et al 2005), which described an
increasing percentage of gallstones with age. The authors should better explain
this finding.
5. Information regarding the family history of gallstones was not available. This
factor may act as confounding variable in the association between gallstones and
NAFLD, because heredity is an important risk factor for gallstone disease. This
aspect should be discussed by the authors.
6. The authors should state that the causal relationship between gallstones and
NAFLD could not be examined by this longitudinal study. However, the study
provides solid evidence that gallstones are associated with NAFLD in female
subjects, NAFLD being an independent risk factor for lithogenesis.
Minor comments:
Some spelling and grammar errors occur in the manuscript, which need to be
corrected by an English translator.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Declaration of competing interests:
I declare that I have no competing interests regarding this manuscript.
Review for 10.1186/s12876-014-0213-y (2014)

Reviewer's report
Title:Non-alcoholic fatty liver disease associated with gallstones in females
rather than males: a longitudinal cohort study in Chinese urban population
Version:2Date:22 September 2014
Reviewer: Frank Tacke
Reviewer's report:
The authors have certainly improved the manuscript. However, most of my
concerns have not been addressed due to methodological reasons (e.g., ALT
levels or information on complications were not available).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/s12876-014-0213-y (2014)

Reviewer's report
Title:Non-alcoholic fatty liver disease associated with gallstones in females
rather than males: a longitudinal cohort study in Chinese urban population
Version:2Date:22 September 2014
Reviewer: Monica Acalovschi
Reviewer's report:
Discretionary revisions
I consider that the Suppl. Table I should be included in the main text, in order to
be easier for the reader to follow the subjects' selection without checking for
supplementary material.
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 I have no competing interests.
Review for 10.1186/s12876-014-0213-y (2014)

Reviewer's report
Title:Non-alcoholic fatty liver disease associated with gallstones in females
rather than males: a longitudinal cohort study in Chinese urban population
Version:2Date:8 October 2014
Reviewer: Constance E Ruhl
Reviewer's report:
Comments to authors are submitted as an attachment.
Level of interest: An article whose findings are important to those with closely
related research interests
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/s12876-014-0212-z (2014)

Reviewer's report
Title:Inhibitory effects of astaxanthin on azoxymethane-induced colonic
preneoplastic lesions in C57/BL/KsJ-db/db mice
Version:1Date:10 March 2014
Reviewer: Jayadev Raju
Reviewer's report:
The manuscript by Kochi T et al. describes a well-designed study to understand
the colon cancer chemopreventive propetries of astaxanthin in experimental
obesity-associated colon cancer. The authors are requested to follow the points
raised below in revising their manuscript:
1. Please mention the duration (8-weeks) of astaxanthin intervention in the
abstract.
2. Page 6: What is the composition of the basal diet CRF-1 (the formula of
Charles River)? Is this different from the conventional AIN diet formulations?At
the least, please provide a reference to the CRF-1 diet.
3. Page 7 (ACF): Please cross-refer the paper by Bird RP - 1987 for ACF
identification, it is okay to use your own reference as a modification.
4. Page 7 (ACF-method), Page 10 (ACF-results and Figure 1B = the ACF per
unit area (cm2) can be confusing. Please provide the total mean number of
ACF/group, mean number of large ACF, and ACF distribution in colon = please
see papers from Tanaka T group or Rao CV group. This may give additional
information supporting the chemorpeventive properties of Astaxanthin. Please
modify results and discussion accordingly.
5. The "no change" results of serum glucose, insulin and adiponectin upon
astaxanthin exposure was surprising; the supporting statement in the discussion
is weak (Page 16, 2nd para). Please include a couple of references with stronger
statement to support this "no change".
6. Figures (Legends) and Tables: Please change the headings from Group 1,
Group 2, Group 3 and Group 4 to None, Astaxanthin, AOM, AOM+Astaxanthin,
respectively. And in results and discussion, please use the same. The use of
Group 1, 2... is very confusing to the reader.
Level of interest: An article of outstanding merit and interest 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/s12876-014-0212-z (2014)

Reviewer's report
Title:Inhibitory effects of astaxanthin on azoxymethane-induced colonic
preneoplastic lesions in C57/BL/KsJ-db/db mice
Version:1Date:9 August 2014
Reviewer: EDUARDO BONDAN
Reviewer's report:
The article shows the potential role of astaxanthin as a chemopreventive agent
against colorectal carcinogenesis in obese individuals. Its methodological
approach is adequate and the results are extremely relevant to the field.
Discussion is pertinent and well fundamented.
There are no recommendations to improve the article.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
There are no conflict of interests.
Review for 10.1186/s12876-014-0212-z (2014)

Reviewer's report
Title:Inhibitory effects of astaxanthin on azoxymethane-induced colonic
preneoplastic lesions in C57/BL/KsJ-db/db mice
Version:1Date:14 August 2014
Reviewer: Nagini Siddavaram
Reviewer's report:
Minor essential revisions.
Following is a detailed critique of the manuscript
Materials and methods
a) Page no 6 – line no 17: treatment with astaxanthin is mentioned as 8 weeks
but in abstract it is mentioned as 12 weeks. Please clarify
b) PCR conditions for real time RT-PCR should be mentioned
c) Page no 8 – line no 22: replace with 8-hydroxy-2#-deoxyguanosine
Results
Western blotting for SOD, GPx, IL-1###IL-6, and TNF-##should be included.
Discussion
Page no 14 – line no 6: replace with TNF-#
List of abbreviations
Line no 1: replace with 8-hydroxy-2#-deoxyguanosine
References
The reference list has to be updated. There are several papers on the subject
published in 2013 and 2014. Of relevance to this manuscript are recent papers
by Hong et al (2013), Tuominen et al (2013), Khan et al (2013), Kavitha et al
(2013) and Kochi et al (2014). The authors should discuss their data in the light
of these findings.
Figures
Figure 1: representative photomicrographs for ACF and BCAC for all groups
have to be included.
Format
Tables have to be presented after figures as per the journal format
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/s12876-014-0212-z (2014)

Reviewer's report
Title:Inhibitory effects of astaxanthin on azoxymethane-induced colonic
preneoplastic lesions in C57/BL/KsJ-db/db mice
Version:3Date:30 October 2014
Reviewer: Jayadev Raju
Reviewer's report:
For authors:
The authors (Kochi et al.) have addressed all queries satisfactorily. There are a
few suggestions the authors could consider as - Minor Essential Revisions, which
the authors can be trusted to make.
1. Table 2: "Body weight" not "Body weigh"
2. Table 2: Please remove superscript "b" from Line 2, Column 4 of Table. Add
superscript "b" to Line 1, Columns 4 and 5 as in "Body weight (g)b" and "(g/100 g
body weight)b". The authors may choose to switch the lettering sequence
between the Mean values (b) and the adipose type (a).
3. Table 3: Please follow the same format as suggested in Point 2.
4. Table 3: The authors may wish to replace Total Number of ACs/colon in
Column 5 to crypt multiplicity (Average number of crypts per foci) data.
5. Table 3: There is no reference to superscript "d" in the table, although there is
mention in the footnote. There seems to be some confusion in assigning
superscript referring to the statistical significance. Please check.
Review for 10.1186/s12876-014-0215-9 (2014)

Reviewer's report
Title:Distress criterion influences prevalence rates of functional gastrointestinal
disorders
Version:1Date:17 October 2014
Reviewer: Phil Austin
Reviewer's report:
I am happy with the changes to the article, however, It still appears that the
authors are separating subjective stress from FGIDs. Given that they state the
biopsychosocial nature of this set of disorders, surely subjective stress is an
integral feature. For me, the consideration of distress is a "given".
Do you have a reference for your Likert scale suggestion for stress, are you
referring to state or trait? If not, are there any previously validated stress-related
measures you could use?
I gather that the Rome IV will include a multidimensional profile that includes
such evaluation.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
Please see my previous comments in first review
Review for 10.1186/s12876-014-0219-5 (2014)

Reviewer's report
Title:A Point-of-Care test for facing the burden of undiagnosed celiac disease in
the Mediterranean area: a pragmatic design study
Version:3Date:27 October 2014
Reviewer: Daniela Basso
Reviewer's report:
The study "A point-of-care test for facing the burden of undiagnosed celiac
disease in the Mediterranean area: a pragmatic design study" by Costa et al. is
aimed to demonstrate that new generation POCT for CD diagnosis is
cost-effective.
Major compulsory revision:
Data do not support conclusions.
A reasonable premise and conclusion for POCT use in CD setting regards only
countries without laboratories facilities. It is not true what stated in the
introduction that ELISAs .."are laboriuos and expensive". In well organized
laboratories, CD serum testing is fast, not expensive and, differently from POCT,
is under continuous monitoring for quality control. Moreover, the statement in the
introduction that POCT are ..."easy-to-perform" is contradicted by the results (fig
1 compared to fig 2 and 3): the rate of classification error increases when POCT
are used by different persons suggesting that it is not so easy to perform. The
other statement which is also the leit motiv of the study is POCT low cost, but no
data regarding POCT cost and comparison with standard ELISA are provided.
An ideal diagnostic test should be 100% sensitive and specific, but this rarely
occurs. For screening purposes, as those claimed for this POCT, sensitivity must
be privileged and should be as high as possible, while a low specificity might be
accepted. This does not appears to be the case of this POCT (PPV of about 90%
and NPV of about 98%).
The results presented in table 2 are not clearly described. i.e. are the No CD
found the number of patients with a confirmed histological diagnosis of CD?
A more detailed analysis of POCT results in comparison with standard ELISA
should be presented. In particular was there any association between POCT
results and ELISA tTG levels? In the paper by Raivio et al (ref 16) it appears
clearly from figure 2 that the lowest ELISA value among those with POCT
positive results is about five fold the cut-off. If this is the sensitivity of POCT this
must be defined.
Some considerations on CD prevalence among the different countries studied
should also be taken into acocunt. By POCT CD was identified in Italy in
19/3559, in Slovenia in 7/1480, in Turkey in 1/771. Do these prevalences fit with
data in the literature?
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/s12876-014-0219-5 (2014)

Reviewer's report
Title:A Point-of-Care test for facing the burden of undiagnosed celiac disease in
the Mediterranean area: a pragmatic design study
Version:3Date:5 November 2014
Reviewer: Stefano Guandalini
Reviewer's report:
This paper is the result of an international collaboration aimed at investigating the
usefulness and feasibility of the widespread use of a point of care diagnostic test
for celiac disease, with focus on its possible implementation in rural or less
affluent areas of the Mediterranean basin.
The study offers valuable findings.
This reviewer only has 2 comments:
1. Even though the English style is overall good and fluent, some awkward
expressions must be polished to further improve its readability. (For instance:
"what the factors are that can influence… " sounds awkward and should be
morphed into "what are the factors that…").
2. The discussion is lengthy and its shortening would contribute to an better flow.
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/s12876-014-0207-9 (2014)

Reviewer's report
Title:Intestinal Capillariasis in the 21st Century: Clinical Presentations and Role
of Endoscopy and Imaging
Version:2Date:26 September 2014
Reviewer: Raymond Tang
Reviewer's report:
The authors reported a case series of 26 patients with Intestinal Capillariasis,
describing the utility of capsule endoscopy, push enteroscopy, balloon assisted
enteroscopy, or CT in improving the diagnosis, in addition to the traditional stool
tests for parasites or ova.
Suggested Discretionary Revisions:
1) If possible, please describe the volumn of diarrhea common seen in this cohort
of patients
2) Because some of the reported endoscopic modalities (eg, balloon assisted
enteroscopy) would require specialized training and the required equipment may
not be widely available in the affected rural areas, it would be helpful if the
authors can propose an algorithm in the choice of these investigations in addition
to the traditional stool tests to allow doctors to understand when a patient should
be referred for further investigations.
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