JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-11-132 (2011)

Reviewer's report
Title:Comparison of accuracy of fibrosis degree classifications by liver biopsy
and non invasive tests in chronic hepatitis C
Version: 1Date:23 January 2011
Reviewer: Sheng-Nan Lu
Reviewer's report:
General comment:
The manuscript by Boursier et al. compared the accuracies of FibroMeter,
Fibrotest and FibroScan in assessing fibrotic stage with a reference of Metavir
fibrosis stage in 4 independent populations of HCV infection. They also assessed
the accuracies of fibrotic stage by local pathologist and expert pathologist with a
reference of consensus reading by 2 expert pathologists. In the result, they
showed us FibroMeter is superior and equal to local pathologist in clinical
practice and expert pathologist in detailed fibrosis classification. In addition,
compared with Fibrotest and FibroScan, FibroMeter had the best accuracy in
assessing binary or detailed fibrosis classification in terms of lower discrepancy
score and grade. The conclusion was sound from their results. However,
prospective validation is necessary to confirm the conclusion.
Major comments:
1. Considering the differences between 6 to 8 stages in detailed fibrosis
classification and 5 histological fibrosis stages, how the authors to define the
accuracy in blood test comparing to pathological stage? For example, is that
correct classification for FibroMeter if the FibroMeter stage is 1.5 (1/2) and
Metavir stage 1 ?
2. There is a modification of detailed fibrosis classification for FibroMeter 3G from
FibroMeter2G. What are the rationales and methods in that modification?
3. FibroMeter 3G is significantly better in correct classification for detailed
classification than for binary classification, which was not seen in other
assessments. The authors might explain it in the discussion section.
Minor comment:
1. There is no description of figure 2 in the result section.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-11-132 (2011)

Reviewer's report
Title:Comparison of accuracy of fibrosis degree classifications by liver biopsy
and non invasive tests in chronic hepatitis C
Version: 1Date:26 January 2011
Reviewer: Salvatore Petta
Reviewer's report:
In the present study Boursier and Colleagues evaluated the accuracy of fibrosis
classifications of non-invasive tests in comparison with liver biopsy. The paper
shows some interesting data, however overall it is not innovative and several
important methodological issues must be reconsidered:
- The study is confusing. The results on different populations should be clearly
showed
- Populations 3 and 4 are relative to two not published studies. Therefore it is not
possible to known the characteristics of these populations
- The results are not original, the same group have recently published the results
of
SNIFF and Fibrostar study (Clin Biochem. 2010 Nov;43)
- In the largest population 2 liver biopsies were not evaluated by a consensus of
expert pathologist.
- The authors should investigate factors associated with discrepancies in different
invasive and noninvasive tests
- How many patients had a liver biopsy < 20 mm?. By excluding these patients it
should be possible to observe an improvement in interobserver agreement
between pathologists
- The characteristic of the study do not allow to consider noninvasive tests better
than liver biopsy in clinical practice
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-11-132 (2011)

Reviewer's report
Title:Comparison of accuracy of fibrosis degree classifications by liver biopsy
and non invasive tests in chronic hepatitis C
Version: 1Date:27 January 2011
Reviewer: Ryota Masuzaki
Reviewer's report:
Boursier et al. examined diagnostic accuracy using several noninvasive tests. It
is well-written and properly reported in accordance with STARD statement.
The authors mentioned that Fibrometer surpassed local pathologists’ reading. It
is not big surprise because it is well known fact that pathological diagnosis is
prone to inter-intra observer variability and blood test is less prone to.
What is the meaning of making fibrosis classification by non-invasive tests?
METAIR score and other pathological fibrosis stages were diagnosed based on
histological morphology. If the authors want to make classifications, it should be
divided based on clinical endpoint.
True endpoints of chronic hepatitis should be decompensation,
hepatocarcinogenesis, and survival. Besides, continuous valuable and its wide
dynamic range are the big advantage of non-invasive test.
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-11-132 (2011)

Reviewer's report
Title:Comparison of accuracy of fibrosis degree classifications by liver biopsy
and non invasive tests in chronic hepatitis C
Version: 3Date:19 June 2011
Reviewer: Sheng-Nan Lu
Reviewer's report:
The authors had answered all the comments by reviewers. The conclusions
based on the results were sound.
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 10.1186/1471-230X-11-132 (2011)

Reviewer's report
Title:Comparison of accuracy of fibrosis degree classifications by liver biopsy
and non invasive tests in chronic hepatitis C
Version: 3Date:22 June 2011
Reviewer: Ryota Masuzaki
Reviewer's report:
No further recommendation.
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-11-131 (2011)

Reviewer's report
Title:Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel
intraepithelial lymphocytosis: case report and literature review
Version: 2Date:4 April 2011
Reviewer: Catherine J Streutker
Reviewer's report:
The manuscript details the case of a patient diagnosed with autoimmune
hepatitis and autoimmune enteropathy with an aberrant CD4+/CD7- T cell
phenotype in the small bowel biopsies.
Issues:
1a.) The diagnosis of autoimmune hepatitis is stated in several areas, but in
other areas is noted to be only 'probable'. I feel the evidence for this diagnosis is
quite weak; liver function tests were only mildly (approximately 2x) elevated, and
ALP was as elevated as the AST/ALT. Serologies were all negative except for
pANCA, which had a very minimal elevation according to the titre noted.
However, as the authors note, the small bowel changes are consistent with
autoimmune enteropathy, regardless of the liver pathology. I think the liver
pathology should be less emphasized in the early portions of the paper.
1b.) Issues are raised in the conclusions section without having been discussed
in the earlier sections - ie the characterization and treatment of AIE. This is not a
place for new information.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-11-131 (2011)

Reviewer's report
Title:Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel
intraepithelial lymphocytosis: case report and literature review
Version: 2Date:17 June 2011
Reviewer: joseph murray
Reviewer's report:
1. Was specific treatment for tropical sprue given, i.e. folic acid and B12, and
what was the patient’s travel history in the months prior to the onset of the
illness?
2. Were T cell gene rearrangements tested?
3. Is it possible this could represent environmental enteropathy or what used to
be called tropical enteropathy, which is endemic in parts of the developing world?
4. Did the patient have any involvement in other organs, such as the stomach?
Was the patient exposed to any irritant medications, such as non-steroidal
anti-inflammatories?
5. Was the intraepithelial lymphocyte clonal – by this, was T cell gene
rearrangement by PCR or flow cytometry undertaken to identify clonal
expansion?
6. What methodology was used for measuring enterocyte antibodies? Was this
an ELISA-based test using extracted antigen or was this indirect
immunofluorescence undertaken on human or monkey intestine? Were goblet
cells diminished or absent?
7. Were any of the CD8 cells positive for markers for cytotoxicity?
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 interests.
Review for 10.1186/1471-230X-11-131 (2011)

Reviewer's report
Title:Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel
intraepithelial lymphocytosis: case report and literature review
Version: 2Date:7 July 2011
Reviewer: Massimo Montalto
Reviewer's report:
The work by Shrinivas Bishu et al. describes a 28 yrs female with autoimmune
enteropathy and autoimmune hepatitis in which steroidal therapy ameliorated
abdominal clinical picture but was not efficacious on liver function.
The paper points on an interesting topic but some doubts have to be underlined.
Major Compulsory Revisions
- the diagnostic criteria to make a correct diagnosis of autoimmune enteropathy
provide a “no response to exclusion diets”: there is no specific references about
this;
- an endoscopic examination of the colon is mandatory to complete an adequate
differential diagnosis;
- as also Authors say, the diagnosis of autoimmune hepatitis is strengthless;
moreover, steroidal treatment did not ameliorate the liver function; in the absence
of autoimmune hepatitis, in this patient the diagnosis of autoimmune enteropathy
cannot be made;
- have the Authors evaluate others atypical autoantibodies such as ASGPR,
liver-pancreas antigens, and liver cytosol?
Minor Essential Revisions
HLA genotypes evaluation (negativity for DQ2/DQ8) should be reported in case
report description and not only in discussion (I think that this finding is more
significant than anti-transglutaminase antibody negativity for exclusion of celiac
disease.)
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-11-131 (2011)

Reviewer's report
Title:Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel
intraepithelial lymphocytosis: case report and literature review
Version: 4Date:15 August 2011
Reviewer: joseph murray
Reviewer's report:
the authors have responded completely to my comments
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-11-131 (2011)

Reviewer's report
Title:Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel
intraepithelial lymphocytosis: case report and literature review
Version: 4Date:9 September 2011
Reviewer: Massimo Montalto
Reviewer's report:
.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-11-129 (2011)

Reviewer's report
Title:Small-bowel mucosal changes and antibody responses after low- and
moderate-dose gluten challenge in celiac disease
Version: 1Date:23 September 2011
Reviewer: Umberto UV Volta
Reviewer's report:
The present paper investigates small bowel mucosal changes and antibody
responses after low- and moderate-dose gluten challenge in celiac disease
patients. Both moderate and low amounts of gluten induced small bowel
morphological damage in 67% of celiac patients. Antibody seroconversion was
observed in 43% of celiac patients studied. This study confirms that low amounts
of gluten can cause significant mucosal deterioration in the majority of celiac
patients and that celiac disease requires a strict compliance with gluten-free diet.
This is an interesting study with solid conclusions in line with the results obtained.
I have only some minor observations:
1) Results section, page 12 : The Authors state that all the 3 antibodies studied
(TG2, EmA and DGP) showed the same antibody titers during gluten challenge.
It would be interesting to know which of the 3 antibodies appeared first after
gluten challenge.
2) Results section, page 12: Small-bowel mucosal TG2-targeted autoantibody
deposits are regarded as a predictor of celiac disease development being found
before the appearance of serum TG2 antibodies. Therefore, it sounds strange
that they become positive after serum TG2 appearance and the Authors should
provide their interpretation for this atypical behavior.
3) Discussion, page 15: The Authors state that celiac serology is not always a
reliable means of assessing gluten-induced harm. We agree with this assertion,
but it would be interesting to evaluate whether the recently introduced test, DGP,
provides some advantage in comparison with TG2 antibodies in this respect.
4) Results, page 10: patients studied were 25, but at 11 line 26 patients are
reported : “moderate IgA-deposits were seen in two and faint in four patients. In
the remaining 20….” Check please this point.
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-11-128 (2011)

Reviewer's report
Title:A randomized double-blind placebo controlled trial to evaluate the value of
a single bolus intravenous alfentanil in CT-colonography
Version: 2Date:26 July 2011
Reviewer: Philippe Ducrotte
Reviewer's report:
This is an interesting protocol about a clinically relevant question. The results are
suitable to improve the realization of CT-colonography.
Major compulsory revisions :
1. Pain assesment is critical. It is unclear why the authors have selected a 1.3
point reduction on a 11-numeric rating scale. This scale is rather unusual. How
can the authors be sure that a 1.3 point reduction is clinically relevant. Moreover,
it is difficult to understand when and how the pain will be assessed. "During the
procedure" is not precise enough. Moreover, it is difficult to understand why "a
score of 10 means the worst pain imaginable" if a 11-numeric scale is used.
2. 90 consecutive patients will be included. But to allow comparisons, the two
groups have to be not different when age and indications will be considered. It is
possible to speculate that pain related to distension could be probably higher in
patients explored for abdominal pain than in asymptomatic patients referred for
screnning. Will patients referred for screening only included ? If not, how the
randomization will be done.
3. For a pertinent clinical answer, the number of patients excluded because of a
contradication for alfentanil needs to be precisely assessed.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare no competing interest
Review for 10.1186/1471-230X-11-128 (2011)

Reviewer's report
Title:A randomized double-blind placebo controlled trial to evaluate the value of
a single bolus intravenous alfentanil in CT-colonography
Version: 2Date:18 August 2011
Reviewer: Andrew D Blann
Reviewer's report:
As per my report
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-11-127 (2011)

Reviewer's report
Title:Change of nitric oxide synthase neurons in ileal myenteric plexus of rat
severe acute pancreatitis
Version: 1Date:19 April 2011
Reviewer: Chuanyong Liu
Reviewer's report:
Major Compulsory Revisions
Lin et al fond that the intestinal transit decreased and the number of nNOS IR
neurons in ileal myenteric plex increased following acute pancreatitis (FAP)), so
the author concluded that increase of nNOS might be the one of the reasons of
the intestinal dysmotility after FAP. This work is interesting but additional
necessary experiments should be performed.
1. In order to certify that the intestinal dysmotility is, at least partly, contributed to
the increased nNOS expression, the effect of nNOS inhibitor pretreatment before
FAP should be investigated.
2. In order to convince the reader that the intestinal dysmotility of the intestinal
transit is caused by the overproduction of NO following FAP, the concentration of
NO in intestine should be measured.
Minor Essential Revisions
There are too many spelling and grammar errors in the manuscript.
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' below
Review for 10.1186/1471-230X-11-127 (2011)

Reviewer's report
Title:Increased proportion of nitric oxide synthase immunoreactive neurons in
rat ileal myenteric ganglia after severe acute pancreatitis
Version: 6Date:20 July 2011
Reviewer: Colin R Anderson
Reviewer's report:
The paper has been largely revised along the lines I requested. However, I
requested three compulsory revisions that have not been made, nor have the
authors responded to the requests. First, I asked whether the Hu neurons
changed in number as this is the only way that the reader can know whether
NOS neurons have increased in number versus whether Hu neurons have
decreased. This has not been answered, but I note that the authors now say they
have counted only 200 Hu neurons at a time, so this implies they don't have the
data to answer my original request. Therefore, I would simply ask that they point
out the impossibility of determining whether NOS neurons have increased or Hu
neurons decreased. Second, I asked whether the increase in NOS expression
was confined to the myenteric plexus. I can't find this information in the revised
version. Third, I requested that they show the size data as a frequency histogram
before and after SAP treatment. This has not been done.
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-11-127 (2011)

Reviewer's report
Title:Increased proportion of nitric oxide synthase immunoreactive neurons in
rat ileal myenteric ganglia after severe acute pancreatitis
Version: 6Date:25 July 2011
Reviewer: Chuanyong Liu
Reviewer's report:
No comments.
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.
Review for 10.1186/1471-230X-11-127 (2011)

Reviewer's report
Title:Increased proportion of nitric oxide synthase immunoreactive neurons in
rat ileal myenteric ganglia after severe acute pancreatitis
Version: 6Date:28 July 2011
Reviewer: Axel Brehmer
Reviewer's report:
No more 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.
Review for 10.1186/1471-230X-11-127 (2011)

Reviewer's report
Title:Increased proportion of nitric oxide synthase immunoreactive neurons in
rat ileal myenteric ganglia after severe acute pancreatitis
Version: 6Date:4 August 2011
Reviewer: Annamaria Szabolcs
Reviewer's report:
The authors made the necessary corrections to the manuscript and addressed
the questions raised by the reviewers. The revised manuscript is suitable for
publication in BMC Gastroenterology.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-11-127 (2011)

Reviewer's report
Title:Increased proportion of nitric oxide synthase immunoreactive neurons in
rat ileal myenteric ganglia after severe acute pancreatitis
Version: 8Date:13 September 2011
Reviewer: Colin R Anderson
Reviewer's report:
I am happy that the authors have complied with my requests by either altering
the manuscript or by clarifying some issues in their letter. I note only one further
issue, which their modified manuscript has made clear. The authors appear to
have statistically analysed percentages using t-tests. Percentages are binomial,
not normal, in distribution and so parametric statistical tests should not be used.
The alternatives are to use a Mann-Whitney nonparametric test, carry out an
arcsine transformation of the percentages before using t-tests or analysing the
raw data (mean number of cells per ganglion per animal in the two groups) by
t-test. Figure 4 also lacks error bars. Please also correct the spelling of
"preperation" (should be preparation) and "gouge" (gauge).
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-11-126 (2011)

Reviewer's report
Title:Development of a validated Patient Reported Symptom Metric for Pediatric
Eosinophilic Esophagitis: Qualitative Methods
Version: 3Date:20 September 2011
Reviewer: Emuella Flood
Reviewer's report:
Major Compulsory Revisions
It is fair to say that a distinction between Flood et al and this study is that in this
study a separate sample was used to perform concept elicitation and cognitive
debriefing. However, the Flood et al symptom diary was developed with patient
input and did involve assessing content validity. The interviews included both
concept eliciation (peformed first with open-ended questions) and cognitive
debriefing, and the diary was revised substantially based on both the concept
eliciation findings (e.g., adding symptoms mentioned by patients) and cognitive
debriefing. As noted in the PRO Guidance, "developers can draft the domains
and items to be measured based on literature and expert opinion. Subsequently,
patient interviews, focus groups and qualitative cognitive interviewing ensures
understanding and completeness of concepts..."
Therefore, text starting on lines 61, 94, 258 and 260 should be revised to reflect
this.
Additionally, it would be beneficial to note the similarities between the two
measures (there is quite a nice overlap in symptoms), as corroborating evidence
suggesting that the item content of PEESS is relevant and comprehensive.
Finally, the issue around recall is not just one of responsiveness, but also
children's ability to think back a month and recall the frequency and severity of
their symptoms, as well as the need to then try to average their experiences over
that period.
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-11-125 (2011)

Reviewer's report
Title:Ringer's Lactate improves liver recovery in a murine model of
acetaminophen toxicity
Version: 1Date:9 March 2011
Reviewer: Jim P. Luyendyk
Reviewer's report:
The manuscript describes the effect of Ringer's lactate administration on
acetaminophen-induced liver injury in mice.
Major comment:
1) Although the results are intriguing, it is challenging to interpret the effect of
RLS on APAP-induced liver injury in the absence of inclusion of an additional
time point (i.e., 48 hours). The results indicate that RLS does not impact
APAP-induced necrosis at 24 hours, but offers protection at 72 hours, the latter
being a time point at which injury is almost completely resolved. Additional
studies are warranted.
2) Inclusion of additional measures of regeneration (i.e, PCNA) would strengthen
the manuscript.
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-11-125 (2011)

Reviewer's report
Title:Ringer's Lactate improves liver recovery in a murine model of
acetaminophen toxicity
Version: 2Date:13 July 2011
Reviewer: Jim P. Luyendyk
Reviewer's report:
1) The authors should include the 48 hour data as a figure in the manuscript, and
described in the results section as opposed to the methods. This will be
beneficial to the reader as the primary conclusion that RLS improves recovery is
based on a single time point at which injury is nearly entirely resolved, based on
ALT activity.
2) The manuscript would benefit by the addition of another biomarker for liver
regeneration/hepatocyte proliferation, such as PCNA staining. The authors note
that they were unable to perform BrdU analysis on account of an animal protocol
issue. It is unclear why PCNA staining cannot be performed on existing paraffin
sections from the 24, 48, and 72 hour time points. Including these data would
substantially increase the impact of the manuscript. Perhaps there is increased
regeneration at 24 hours not reflected by ALT activity at that time point.
Minor comment: The new text (currently in methods) describing the 48 hour data
should read “did not show statistically lower serum…”
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:
no competing interests.
Review for 10.1186/1471-230X-11-125 (2011)

Reviewer's report
Title:Ringer's Lactate improves liver recovery in a murine model of
acetaminophen toxicity
Version: 2Date:17 July 2011
Reviewer: Cynthia Ju
Reviewer's report:
If it is possible to extend the dealine for the manuscript resubmission, it is good to
include the BrdU (or PCNA) data to support the authors' conclusion.
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-11-125 (2011)

Reviewer's report
Title:Ringer's Lactate improves liver recovery in a murine model of
acetaminophen toxicity
Version: 3Date:29 September 2011
Reviewer: Jim P. Luyendyk
Reviewer's report:
The 48 hour clinical chemistry data are sufficiently critical as to deserve inclusion
in the results section at a minimum, but should be included in the figure package.
It seems likely that issues with figure panel arrangement can be overcome to
accomodate this change. It is particularly important to include these data insofar
as the authors indicate with respect to PCNA data that necrosis is reduced from
25% to 2% by RLS treatment, despite a lack of significant change in ALT at
either 24 or 48 hours.
It is surprising that PCNA-positive hepatocytes were not present in livers of
APAP-treated mice and that the vast majority of PCNA positive cells were
inflammatory cells. Previous studies have definitively shown that hepatocytes
bordering areas of necrosis express PCNA during injury progression.
Clarificiation is required.
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-11-124 (2011)

Reviewer's report
Title:Lactase non-persistent genotype influences on dairy product consumption
and gastrointestinal symptoms in Northern Russians
Version: 1Date:26 April 2011
Reviewer: Mauro Congia
Reviewer's report:
Major Compulsory Revisions
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-11-124 (2011)

Reviewer's report
Title:Lactase non-persistent genotype influences milk consumption and
gastrointestinal symptoms in Northern Russians
Version: 2Date:24 June 2011
Reviewer: Andrew Szilagyi
Reviewer's report:
The rereview of the manuscript basically answers questions I posted on teh first
pass of this paper. I think the authors have adequately answered these and I
have no objections to proceeding with the 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-11-124 (2011)

Reviewer's report
Title:Lactase non-persistent genotype influences milk consumption and
gastrointestinal symptoms in Northern Russians
Version: 3Date:7 October 2011
Reviewer: Mauro Congia
Reviewer's report:
The authors have adequately answered to the questions and there are no
objections to proceeding with the publication
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-11-122 (2011)

Reviewer's report
Title:Evaluation of gastrointestinal symptoms in different patient groups using
the visual analogue scale for irritable bowel syndrome (VAS-IBS)
Version: 2Date:17 September 2011
Reviewer: Gabrio Bassotti
Reviewer's report:
The authors evaluated GI symptoms in different pathologic groups by means of a
VAS scale they proposed and validated, to see whether it is possible to
discriminate between groups on a symptom basis. My comments are detailed
below.
MAJOR COMPULSORY REVISIONS
1. Introduction. I do not feel that it is difficult to distinguish, even on clinical
grounds, between IBS, ED, and CIPO. The last condition, in particular, displays
such peculiar features that it is often seen by surgeons…besides, what is the
difference between ED and CIPO? Please specify here.
2. Materials and Methods. Controls. Using medical staff samples as controls
might not be a good idea, in that these are subjects biased toward a greater
attention toward medical details. I suggest the authors use a more appropriate
control group (e.g., random sample from general population).
3. Materials and Methods. Patients with dysmotility disorders. Recruitment of
these patients seems to have been done retrospectively, since subjects were
included undergoing laparoscopy in the last 10 years. Again, the difference
between ED and CIPO as presented here by the authors is not convincing.
4. Materials and Methods. As a further group, the authors chose patients with
pSS. Again, I wonder whether these subjects are appropriate. To test their
hypothesis, the authors should compare IBS patients with more appropriate
patients groups, such as fibromyalgia patients, celiac disease patients, and
patients with food allergy/intolerance.
5. Again, concerning recruitment, it appears that the authors were aware “a
priori” of the patients’ diagnoses, introducing a further bias. A more appropriate
way of conducting such a study would have been to administer the scale in a
prospective manner, during an established period of time, to all patients
evaluated for suspected functional GI disorders.
6. The scale was not administered in the same manner to all subjects
participating to the study.
7. Results. It is not surprising that pSS patients had less GI complaints that GI
disorders; things could probably be different if scleroderma patients were
selected, in whom GI involvement is often present and important.
8. The conclusions are misleading; on these basis the VAS score seems of no
utility in this setting.
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-11-122 (2011)

Reviewer's report
Title:Evaluation of gastrointestinal symptoms in different patient groups using
the visual analogue scale for irritable bowel syndrome (VAS-IBS)
Version: 4Date:21 October 2011
Reviewer: Gabrio Bassotti
Reviewer's report:
I have no other comments
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-11-122 (2011)

Reviewer's report
Title:Evaluation of gastrointestinal symptoms in different patient groups using
the visual analogue scale for irritable bowel syndrome (VAS-IBS)
Version: 4Date:29 October 2011
Reviewer: Giovanni Barbara
Reviewer's report:
The authors have addressed all the issues raised in my previous review and
changed the manuscript accordingly. I have no further comments on this
manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
no COI
Review for 10.1186/1471-230X-11-121 (2011)

Reviewer's report
Title:The impact of laxative use upon symptoms in patients with proven slow
transit constipation: Are infrequent hard stools a reality?
Version: 1Date:12 July 2011
Reviewer: Yasuko Maeda
Reviewer's report:
This is a well written paper on a difficult topic.
A few things that need further explanation.
1. Some of the patients appear to have had bowel openings on daily basis which
does not fulfill Rome III criteria. Was this a cohort of the patients considered for
SNS then you selected those with slow constipation on scintigraphy? The
inclusion crieria is not entirely clear.
2. Was any patient using enema or suppository for evacuation difficulties?
3. What about data on hard stools also? This should be presented to give clearer
picture on association between hard/soft stool and laxatives.
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-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 1Date:12 August 2011
Reviewer: Anthony F Shields
Reviewer's report:
The authors have studied the use of 18F-FDG PET (fluorodeoxyglucose positron
emission tomography) for the evaluation of patients with locally advanced
pancreatic carcinoma (LAPC) who are to receive chemoradiotherapy. In this
study they have evaluated the use of PET in staging these patients as well as
assessing treatment response, measured as overall survival, and rate of
resection. They provide some useful data on the use of PET in this group of
patients, but some clarifications are needed.
Minor Essential Revisions
1- When during the 12 weeks post-radiation was PET done? They report that
they gave the gemcitabine on 3 week cycles for 4-6 course or 12-18 weeks. So
were all PETs done at completion or during the gemcitabine?
Major Compulsory Revisions
2- Their division of responding and non-responding patients seems arbitrary.
They said they split patients “response greater versus lesser than the mean
difference.” It is not clear that this is the best division. In fact, they point out that
this divided their patients into 21 patients with a better PET response and 11 with
a poorer response. How about using the median difference, which would divide
these into two equal groups or ROC analysis to pick the cut point?
3- They used the SUVmax as their measure of activity, but this really just
represents a single pixel over the whole tumor. It can be subject to significant
noise. Furthermore, it may be hard to generalize SUVmax from one scanner to
another since the pixel size and resolution can very. Did they also try to use
SUVpeak or some variation of SUVmean? This would be very helpful. Some
investigators have also tried other approaches such as total metabolic volume
(SUV x volume), but this still requires one to set some boundaries on the tumor.
4-The definition of locally advanced and unresectable pancreatic cancer is often
confusing and varies from physician to physician. How did they define it? All they
state is that “Disease extent was determined by radiological studies and
laparoscopy/laparotomy.” What imaging studies were done, e.g did they do CT
with a pancreatic protocol, MRI, EUS? How many patients were judged
unresectable by imaging alone vs at laparotomy?
5-Table 1 should be deleted, since they just give the EORTC PET response
criteria and is not needed in this manuscript. Given the limited number of patients
in the study a table summarizing the results in each patient would be helpful. This
could include the baseline and post-treatment SUV, the PFS and OS and
resection results. This way others could plot and analyze the data as they saw fit.
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-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 1Date:20 August 2011
Reviewer: Lena Specht
Reviewer's report:
This manuscript examines the prognostic value of PET-response to
chemoradiotherapy in 32 patients with locally advanced pancreatic cancer.
Patients had a FDG-PET-CTscan before therapy (which was used for planning
radiotherapy) and 12 weeks after the end of treatment. They show that a good
metabolic response was associated with a significantly better prognosis. This is
in accordance with findings in many other tumour types, but is has not been
demonstrated extensively in pancreatic cancer. The authors mix local and distant
recurrences, although they would seem to be qualitatively different, the local
ones due to the ineffectiveness of chemoradiotherapy, the distant ones due to
lack of effectiveness of the chemotherapy. However, with so few patients this is
probably the best that can be done.
Major compulsory revision: The authors claim that the PET-response had
independent prognostic importance when other factors were taken into account
in multivariate analysis, using the Cox model. However, they do not state which
other factors were taken into account (are all the really important ones
included?), how these factors were scored in the analysis, how the analysis was
carried out (e.g., forward or backward selection), and which factors were in the
final model. This information is crucial when evaluating whether PET-response
really has independent prognostic significance. When the multivariate analysis is
done it must be taken into account that there are only 26 events (failures) in total,
and that therefore only a limited number of different factors can be analysed in a
Cox model at the same time. Also, the assumptions underlying the Cox model
(proportional death intensities) must be demonstrated to hold. Statistical
assistance is advised.
Minor essential revision: The numbers in Table 2 to not add up. With a total
number of patients of 32, 16 males and 8 females is too little.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 2Date:30 September 2011
Reviewer: Anthony F Shields
Reviewer's report:
No further comments.
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 have no competing interests.
Review for 10.1186/1471-230X-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 2Date:15 October 2011
Reviewer: Lena Specht
Reviewer's report:
The authors have responded to the points made by the reviewers.
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-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 2Date:26 October 2011
Reviewer: Devin Schellenberg
Reviewer's report:
I would like to thank the authors for a very detailed response to all comments
from the reviewers. I believe the updated manuscript to be significantly improved.
I still feel the first few paragraphs of the discussion are slightly tangential to the
focus of the paper, but that is not a reason to dismiss them.
Below are a few things i noticed re-reading the manuscript. None are concerning:
1) Abstract - Results section "8.4versus 3.8" (there is a space missing after 8.4)
2) Methods - 2nd sentence reads awkwardly as patients don't have histologic
proof of unresectability... i would suggest something like :32 patients with
unresectable, non-metastatic LAPC with histologic proof of malignancy were
enrolled..."
3)Methods - "biops(y)ies" can probably be written as "biopsies"
4) Results - 2nd paragraph "26 patients experienced some failure during the
disease course" should be re-written as "26 pts experienced some failure during
the follow-up period"
5) Results - last sentence - i'd add the median OS for those with who went on to
resection, but that is just because as a reader i wanted to know
6) Conclusions - there are 2 commas in a row after "And second,, significantly..."
7) I'm pretty sure Reference 44 has been published (within the last 2 months or
so)
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:
No competing interests
Review for 10.1186/1471-230X-11-120 (2011)

Reviewer's report
Title:Surgery for fistula in ano in a specialist colorectal unit: a critical appraisal
Version: 1Date:28 July 2011
Reviewer: gennaro rosa
Reviewer's report:
This article is a case report,well detailed but some difficulty of interpretation and
some imprecision of terms and ratios reported are in the text.
An author, Shulka, quoted in discussion, is not reported in the references.
When I reviewed single paragraphes of the article I noted :
ABSTRACT- FIRST PARAGRAPH:
The follow-up range is acceptable,even if 3.8 months reported as the lowest is
too short to evaluate results of fistula-in-ano operation.
INTRODUCTION-SECOND PARAGRAPH :
The cutting seton procedure is well explained,but the surgical cutting after loose
seton is not described.
PATIENTS AND METHODS-THIRD PARAGRAPH:
Authors write that their cases were classified according to Parks’
classification,but in this one submucosal/superficial fistulae are not
included.Other classification,based on Parks’ ideas account them.
RESULTS-FOURTH PARAGRAPH:
Comorbidities have been treated at the same time of the fistula operation or not ?
Loose seton was the only treatment on 94 patietns ( 40.7% ) We know that loose
seton alone does not heal anal fistulas.
Authors must clarify better this detail in connection with the ratio of the cured
patiens reported.
Recurrence report,even if well detailed,is scattered and not on the whole
understandble; it would be better to modulate again it and make a synthesis.
Results explanation displays the surgical approach difficulties in many cases,but
is too detailed and forces the comprehension’s reader.
DISCUSSION- FIFTH PARAGRAPH:
Shulka et al. quoted as a reference with n.21 in the article is not included in the
references paragraph. 26 fistulae with Crohn disease on the whole 231 are not
24.3% but 11.25%.
CONCLUSION:
The article is acceptable with MINOR ESSENTIAL REVISIONS, as pointed out
from the paragraphes review.
My advice on pubblication is positive.
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 not competing interests.