JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-14-21 (2014)

Reviewer's report
Title:Chronic gastritis in China: a national multi-center survey
Version:2Date:6 January 2014
Reviewer: Yeong Yeh Lee
Reviewer's report:
Reviewer’s report
Discretionary revisions
It is much appreciated for authors to respond to all the queries meticulously. I
totally agree with authors, in the discussion section, that endoscopic appearance
and histology of chronic gastritis are not ideal for precancerous lesions and
perhaps other biomarkers may then be helpful including genetic markers, for
example Maran S et al. World J Gastroenterol 2013; 19: 3615-22., even though
the work is still preliminary. I also agree with authors that eradication of H. pylori
in chronic gastritis is still controversial. On the other hand, a “good H. pylori is a
dead one”, and this has some support from literatures as well as epidemiological
evidence, for example Lee YY et al. Helicobacter 2013; 338-46. These are
interesting points to be considered for discussion in the paper.
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-14-22 (2014)

Reviewer's report
Title:Do high risk patients alter their lifestyle to reduce risk of colorectal cancer?
An observational study
Version: 1Date:26 September 2013
Reviewer: Annie Anderson
Reviewer's report:
This paper reports interesting work on perceived risk of CRC and reported
changes in lifestyle.
There are a number of issues to address
Major
1. The details of the collection tool are provided elsewhere but some information
is required to assess the current manuscript e.g the reliability and validity of the
tool to collect data on reported changes. There are three relevant issues here a)
How were questions phrased with respect to the time frame ?b) what magnitude
of change was reported (and ofcouse what is the validation) c) how was the “not
applicable” category dealt with (e.g. no changes in smoking because participant
did not smoke, or drink alcohol etc)
2. There are a number of papers reporting qualitative issues related to population
colorectal cancer screening (and adenoma bearers)and lifestyle highlighting low
awareness of risk and these should be cited in the discussion rather than
references to breast cancer risk. Overall authors seem to steer away from
qualitative literature but the following papers would contribute to discussion.
Qualitative papers- low risk awareness
Stead M, Caswell S, Craigie AM, Eadie D, Anderson AS; BeWEL team.
Understanding the potential and challenges of adenoma treatment as a
prevention opportunity: insights from the BeWEL formative study. Prev Med
2012;54(1):97–103.
Dowswell G, Ryan A, Taylor A et al. Designing an intervention to help people
with colorectal adenomas reduce their intake of red and processed meat and
increase their levels of physical activity: a qualitative study. BMC Cancer
2012;12:255.
3. In text the authors refer to reference 9 to support the statement that “patients
may adopt healthy behaviours around the time of CRC screening, but this
reference appears to relate to breast cancer screening
4. Page 11 authors suggest that risk of crc per se is important for promoting
change without medical professional intervention, but I am not sure if we can be
confident that no advice was given. In our family history clinics all patients get a
booklet about relevant lifestyle
5. The final para of discussion needs re-writing
6. There are two possible additions to the discussion… because people report
subjective lifestyle change it does not mean they achieve a relevant magnitude of
change to meet current guidance for that healthy behaviour (even in people who
say changed “very much so”), so prompting change in itself is rarely likely to be
adequate and additionally it may not be sustained. The opportunity “ teachable
moment” for health professionals to promote lifestyle change should also be
discussed.
Minor
7. The figures should each have a title
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 interest
Review for 10.1186/1471-230X-14-22 (2014)

Reviewer's report
Title:Do high risk patients alter their lifestyle to reduce risk of colorectal cancer?
An observational study
Version: 1Date:14 October 2013
Reviewer: Karen Bronner
Reviewer's report:
Major Compulsory Revisions
1. The last paragraph of the background should be elaborated.
A growing body of evidence has revealed correlations between risk perception/
anxiety/ concern on medical condition and health behaviours. You are advised to
provide more literature review on this issue and specify what is already known
and what needs further investigation.
2. Methods are not well described and structured. It is recommended to provide
more details in particular about the study methods and measures rather than
writing the following sentence: “the methods are reported in greater detail
elsewhere”.
3. Methods: some definitions are missing (especially for non-New Zealanders
readers), as follows: NZGG category 1-3, The NZ Dep2006 index of deprivation
ordinal scale, scoring method of GAD-7.
4. Methods: the construct of the knowledge assessment isn’t clear (was it a
general question regarding CRC risk factors or specific questions on the
awareness of each recognized risk factor to develop CRC?). It is important to
note that lack of knowledge on specific risk factor may serve as a barrier to
lifestyle alteration.
5. Results: please address the correlation between the 3 perceived risk
perception classification (appropriate/underestimate/overestimate) and the
likelihood of behavioural change, e.g. fibre, red meat, alcohol, as well as
correlation to level of knowledge about risk factors.
6. Discussion: the last paragraph on page 11,which provides possible reasons
from the literature for higher likelihood of dietary change should be connected to
the first paragraph that reports this finding. Can you provide reasons which are
based on the collected data rather than previous studies?
7. Discussion: “it may be easier to change diet than alter smoking, alcohol intake
or body weight” - could you support this argument with relevant studies or it is a
personal opinion?
Minor Essential Revisions
1. Please, add title to Figure 1.
2. The study cohort was comprised of a limited age group (56.5-59.3)
and almost only NZ European- it is advisable to address the homogeneity of the
cohort in the result and limitation sections.
3. Please consider using the following terms: introduction, study population/study
design, data collection and study measures instead of background, participants
and definitions, respectively.
Discretionary Revisions
None.
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-14-19 (2014)

Reviewer's report
Title:Endoscopic findings in uninvestigated dyspepsia
Version: 1Date:4 April 2013
Reviewer: Peter Malfertheiner
Reviewer's report:
This is a prospective study about endoscopic findings in uninvestigated
dyspepsia. It is a single centre study performed in Sao Paulo, and definitely of
interest, especially as it presents data from an emerging country such as Brazil.
The manuscript needs further improvement of written English and should be
reviewed by a native speaker. There are some weakness in the interpretation
and discussion of the data.
Special remarks:
- Data needs to presented with range and confidence intervals
- The diagnosis of GERD needs to specified in erosive reflux disease. The
diagnosis of NERD can not be made as reflux symptoms are considered an
exclusion criteria and no other diagnostics were performed.
- What are the “other” endoscopic findings of the esophagus (table IV)
- What happened to the patients that were obviously screened but excluded?
What were the various for exclusion?
- Did the investigators take biopsies for histology also? If so, the diagnosis of
“gastritis” should be specified by histopathological finding.
- What was the pattern of gastritis? More antrum-predominant, corpus
predominant or pangastritis?
- What was the specificity of symptoms? What defines “tipic” and “atipic”?
- discussion and conclusion of the data needs more pointed abstraction of the
raw data, than just a enumeration and iteration of the results.
- “test and treat” strategy for H. pylori needs more detailed discussion for the
special situation in Sao Paulo as an area with high H. pylori prevalence (>20%).
Level of interest: An article of importance in its field
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.
Review for 10.1186/1471-230X-14-19 (2014)

Reviewer's report
Title:Endoscopic findings in uninvestigated dyspepsia
Version: 1Date:10 May 2013
Reviewer: Rodrigo Machado
Reviewer's report:
This is a straight forward study that evaluates upper GI endoscopy for
investigating dyspepsia in a developing country.
Minor essential revisions:
1. Background: There is a conceptual problem in the last paragraph. The test and
treat strategy for dyspepsia is clinically suitable and cost-effective for regions with
high prevalence of H pylori (see PMID: 17608775 and Maastricht IV). The
strategy is not feasible in low prevalence countries, where the low positive
predictive value of serology precludes it. Therefore, the sentence should be
corrected.
2. Methods. A reference should be provided for the alarm symptoms in the
second paragraph. There are several definitions of alarm symptoms. Ref 16
(cited in Background), for instance, includes persistent vomiting,
lymphadenophaty and family history of upper GI cancer. The authors chose a
more strict definition, and it should be cited the rationale for that.
3. Methods and Discussion. The cross cultural validation of the LDQ should be
cited. If not available, it should be also cited in Discussion (an important
limitation).
4. Results. The aim of the study is “to assess the diagnostic yield of EGD “. So,
patients without an EGD should be excluded (therefore, all tables with 292
patients).
5. Results. Also, there were 306 eligible, but only 282 were included. 24 patients
were lost (< 8%, a pretty reasonable rate), and the reasons should be described.
Discretionary revisions:
1. Methods. First line of methods “... which provides open-access endoscopy. “ (if
it still provides open-access endoscopy, if not “which used to provide”), without
the phrase defining open-access endoscopy (redundant) (delete “that did not
require referral to specialists first.”.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-19 (2014)

Reviewer's report
Title:Endoscopic findings in uninvestigated dyspepsia
Version:3Date:7 November 2013
Reviewer: Marek Brabec
Reviewer's report:
This is an interesting applied study of considerable practical interest. It uses
standard statistical tools to reach appealing conclusions. It should be published.
Below, we list some points and details which should be modified/corrected before
the publication.
The sentence “The mean age was 44 years and women comprised 65% of the
population.” is highly misleading and should be changed. The word “population”
is completely inappropriate here. Something like “sample” is to be used.
The word “sensibility” on the vertical axis of the Figure 1 should be replaced by
“sensitivity”.
In the Figure 2 (UDE-Score), there appears Age as one of the explanatory
variable. Reading the part of the text referring to the Figure 2, it is probably
wrong to write 0.7age in the formula. From the text on page 8 (“…logistic
regression of age > 48 years...”), it seems that we should have something like:
with being an indicator function (assuming 1 if its argument is true and 0 if it is
false). This would amount to 0.7*age for age over 48 and 0 for age less than or
equal to 48. Alternatively, we might have which amounts to 0.7 for age over 47
and 0 otherwise. One cannot tell from the text what of the two possibilities (or
even some other, more exotic variant) was used. The paper should specify the
model and the score unambiguously (as it would be quite dangerous for a user to
take one interpretation, where in fact the other was used by the authors). This
can be achieved via indicator function formalism (being used as one component
in the full model/score specification) as above, or via other description.
Nevertheless, the description should be clear and unequivocal.
Review for 10.1186/1471-230X-14-19 (2014)

Reviewer's report
Title:Endoscopic findings in uninvestigated dyspepsia
Version:4Date:26 December 2013
Reviewer: Marek Brabec
Reviewer's report:
The authors corrected things indicated in the previous review. Readability and
precision of the text improved consequently and the paper is now ready for
publication.
Review for 10.1186/1471-230X-14-20 (2014)

Reviewer's report
Title:Multiple aseptic splenic abscesses in a 15 year old patient - role of
anaerobic bacteria?
Version:3Date:10 December 2013
Reviewer: Maria Tsolia
Reviewer's report:
The authors describe the case of a 15-year old adolescent girl with multiple
aseptic splenic abscesses without Crohn’ s disease. Although there was some
improvement in patient’s symptoms after administration of antibiotics such as
meropenem and metronidazole complete resolution of the abscesses was
achieved only with corticosteroid treatment.
This is a nice case report describing a rare clinical entity since there are only
scarce similar reports in the literature. Physicians must be able to recognize this
disease which requires immunosuppressive treatment.
The possible role of anti- anaerobic treatment, namely metronidazole, is raised
since there was some initial response to the combination of meropenem and
metronidazole including healing of accompanying pharyngeal ulcers and
improvement of inflammatory markers. However, there was no effect on abscess
size and number which increased upon discharge and new ones developed only
to resolve after administration of prednisone in combination with metronidazole.
Comments
Minor essential revisions
1. Although it its evident that the disease was controlled only after corticosteroid
treatment the role of metronidazole is less clear. The improvement detected after
initial treatment with meropenem and metronidazole should be described in more
detail (resolution of fever? How improved were the inflammatory markers on
initial discharge?). Did the patient receive any antibiotics upon discharge the first
time?. In addition, no conclusions can be drawn about the contribution of
metronidazole to disease resolution since it was administered together with
prednisone.
2. Follow-up time: was it enough to detect Crohn’ s disease? How long after the
development of abscesses did Crohn’s disease manifest in the published
reports?
3. Some spelling errors need to be corrected: an-/hypoechoic (un-/hypoechoic),
Clindamycine (clindamycin), quantiferone (Quantiferon test), thyreoiditis
(thyroiditis)
Discretional revisions
4. It would be useful if the authors could briefly summarize the cases previously
described in the literature among children (if any) and adolescents as well their
clinical and laboratory characteristics.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-20 (2014)

Reviewer's report
Title:Multiple aseptic splenic abscesses in a 15 year old patient - role of
anaerobic bacteria?
Version:3Date:12 December 2013
Reviewer: Henrik Koehler
Reviewer's report:
The author report on a interesting case of a boy with aseptic splenic abscesses.
Major Revisions: None
Minor Revisions:
The title issomewhat misleading. Anaerobic bacteria are not the focus of this
report.
What happened to the apparently subclinical thyreoiditis? Treatment?
(The usual course of Hashimoto's thyroiditis is gradual loss of thyroid function.
Among patients with this disorder who have mild (subclinical) hypothyroidism and
the presence of thyroid antibodies, overt hypothyroidism occurs at a rate of about
5 percent per year.)
Inflammatory bowel disease can not be ruled by out by one colonoscopy. Did the
authors also look for inflammatory markers in the stool, like calprotectin or
lactoferrin?
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-18 (2014)

Reviewer's report
Title:Effects of paracentesis on hemodynamic parameters and respiratory
function in critically ill patients
Version:1Date:1 November 2013
Reviewer: Alexander Koch
Reviewer's report:
Phillip an collegues report on the "Effects of paracentesis on hemodynamic
parameters and respiratory function in critically ill patients". Main findings are that
paracentesis in critically ill patients is safe regarding hemodynamic
function, renal function and intervention-related complications. Paracentesis in
critically ill and mechanically ventilated patients results in immediate and
sustained improvement of respiratory function. The manuscript is well written and
data presentation is sound. A highlight of the study is the thorough analysis of
multiple cardiovascular and pulmonary parameters. The authors accurately
mention the limitations of thir study. Nevertheless, i have some minor remarks:
1. The backgroud section should be more focused on ICU patients.
2. the fact that albumin substitution was at the discretion of the treating ICU
physician and was not performed following national/international guidelines
should be adressed in the limitations section.
3. it would be very interesting, if the authors would present data on serum
albumin/protein levels before and after paracentesis.
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-14-18 (2014)

Reviewer's report
Title:Effects of paracentesis on hemodynamic parameters and respiratory
function in critically ill patients
Version:1Date:10 December 2013
Reviewer: Erwin Gäbele
Reviewer's report:
In the manuscript „Effects of paracentesis on hemodynamic parameters and
respiratory function in critically ill patients“ Philipp and coworkers demonstrated
that paracentesis in patients with advanced liver cirrhosis was safe regarding
cardiocirculatory parameters and significantly improved respiratory function in
mechanically ventilated patients.
Specifically, mean arterial pressure and systemic vascular resistance index,
using standard monitoring procedures, initially showed a slight decrease but
stable parameters 6 hours after paracentesis. On the other hand lung injury
score and PaO2/FIO2 improved at all timepoints after paracentesis.
Univariate analysis found an association between the amount of ascites, lung
injury score and PaO2/FIO2. In addition multivariate regression analysis
confirmed lung-injury score used and the amount of ascites removed as
independent parameters for improvement of the respiratory function. In addition
an improvement of the renal function was observed.
In summary this is nice prospective study which demonstrated hemodynamic
stability on the one hand and improvement of the respiratory function on the
other hand, probably due to optimized volume monitoring and therapy after
paracentesis. The effects were most likely due to a reduction of intraabdominal
pressure thereby limiting respiratory complications. Although this study was only
performed in a small cohort, large volume paracentesis should be performed in
advanced liver cirrhosis combining adequate hemodynamic monitoring and fluid
substitution.
Methods and presentation of the manuscript are excellent. If the authors could
give a more detailed explanation for the improvement of renal function despite
changes of the mean arterial pressure after 6 hours the manuscript should be
accepted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Review for 10.1186/1471-230X-14-16 (2014)

Reviewer's report
Title:Detection of small ( < 2 cm) pancreatic adenocarcinoma and surrounding
parenchyma: correlations between enhancement patterns at triphasic MDCT and
histologic features.
Version: 1Date:20 May 2013
Reviewer: Marcella Arru
Reviewer's report:
No Major Compulsory Revisions.
Minor Essential Revisions:
1. Some abbreviations are not defined in the text:
- CT (computed Tomography): in “Introduction”, 2nd paragraph
- MSCT (Multislice CT?): in “Multislice CT protocol”, 1st paragraph
- HU(Hounsfield Unit); in “Multislice CT protocol”, 2nd paragraph
- kVp and mA: in “Multislice CT protocol”, 3th paragraph
2. Typing missing/errors:
- In “Images analysis”, 6th paragraph: “When the difference in attenuation
between the lesion and upstream or downstream parenchyma presents values
<10 HU, the lesions ARE note recognizable...”
- In “Statistical analysis”, 1st paragraph “(in HU# } SD)”: its means: “mean ± SD”?
- In “Results”, 2nd and 3th paragraphs: “hypo-” is “hyperdense”
Discretionary Revisions
1. In “Materials and methods,” “Patient selection”- first paragraphs and
“Histological evaluation” - first paragraph: Pancreatic surgery is better defined as:
“pancreaticoduodenectomy, distal pancreatectomy or total pancreatectomy”
2. In “Discussion”, 10th paragraph: “The quantitative analysis at triphasic MDCT
increases tumor detection with respect to visual analysis (sensitivity=100%
versus 92.1%)”: It is not clear which are the data in “Results” that support 92.1%
sensitivity of visual analysis.
3. In “Discussion”, 11th paragraph: A limit of the study consists, not only in its
retrospective nature, but also in the characteristics of patients enrolled in the
study, which were all surgically treated patients for a small PDA detected at
MDCT, not including patients with an hypothetical misdiagnosis.
4. In “Discussion”, 12th paragraph: The correlation of the histologic features
(available obviously only postoperatively) with enhancement patterns at CT could
be essential for improve research on methods to detect isoattenuating PDA, but
can not have a direct clinical practical role. I suggest to delete “in the clinical
practice”.
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-14-15 (2014)

Reviewer's report
Title:High dose multiple micronutrient supplementation improves villous
morphology in environmental enteropathy without HIV enteropathy: results from a
double-blind randomised placebo controlled trial in Zambian adults.
Version:1Date:31 October 2013
Reviewer: Andrew Veitch
Reviewer's report:
The study is of interest, and important in stimulating further research into tropical
enteropathy which is ubiquitous in sub-Saharan Africa. The morphological
changes in the small bowel following MM supplementation are statistically
significant although their biological significance warrants further study. This study
is limited by small numbers and the fact that the data has been gleaned from
another study with the intention to examine the effect of vaccines rather than
micronutrient supplementation. The main weakness of this study is a lack of a
baseline jejunal biopsy prior to randomization to MM supplementation or placebo.
The effect of MM supplementation is therefore inferred rather than directly
measured over a period of time. These limitations and their effect are discussed
appropriately in the discussion. Statistical methods are appropriate, though
confidence intervals are wide as would be expected with small numbers.
The study does however add positively to the literature, and is worthy of
publication.
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-14-15 (2014)

Reviewer's report
Title:High dose multiple micronutrient supplementation improves villous
morphology in environmental enteropathy without HIV enteropathy: results from a
double-blind randomised placebo controlled trial in Zambian adults.
Version:2Date:31 December 2013
Reviewer: Angus Scrimgeour
Reviewer's report:
Major Compulsory Revisions - none.
Minor Essential Revisions - none.
Overall: the authors have answered all queries/concerns with satisfactory detail
and clarity. Sections of the INTRODUCTION and DISCUSSION have been
edited as suggested/recommended by this reviewer. The manuscript is much
improved.
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-14-14 (2014)

Reviewer's report
Title:Duodenal mucosal damage is associated with proliferative activity of
Brunner's gland hamartoma: a case report
Version: 2Date:3 October 2013
Reviewer: Piero Chirletti
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: 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-14-14 (2014)

Reviewer's report
Title:Duodenal mucosal damage is associated with proliferative activity of
Brunner's gland hamartoma: a case report
Version: 2Date:14 October 2013
Reviewer: Philippe Marteau
Reviewer's report:
Kim et al. recently analyzed clinicopathologic features and mucin expression in
25 Brunner’s gland proliferating lesions (Dig Dis Sci (2013) 58:194–201). This
paper should be quoted much more in detail and makes the single case
presented here much less original.
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
No conflict of interest
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version: 1Date:20 May 2013
Reviewer: Min Fang
Reviewer's report:
Increasing evidence suggests that the hydrogen treatment is associated with
anti-inflammation, including myocardial IRI. However, the precise effect and
mechanism of hydrogen-enriched saline treatment in liver injury is still unclear. In
this report, the authors suggest that hydrogen-enriched saline treatment plays a
protective role in liver IRI setting. The result is interesting. However, I have some
concerns:
The manuscript just described the application of the hydrogen-enriched saline
attenuates the liver ischemia reperfusion injury, this is a phenomenon, the
authors should investigate the relevant mechanisms in depth. In addition,
previous other studies already reported the hydrogen-enriched saline has
anti-inflammation such as in the settings of sepsis and myocardial IRI, so the
novelty is limited.
Major points
1. The manuscript has mentioned hydrogen has anti-oxidative effects. However,
the study has no relevant data. Reactive oxygen species (ROS) must be
measured in the liver IRI setting.
2. NF-#B is a crucial nuclear factor controlling the inflammatory cytokines. The
hydrogen-enriched saline influencing the NF-#B signaling must be investigated.
Minor Points
1. In figure 1 legend, n=96? Does repeat the experiments 96 times?
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
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version: 1Date:30 May 2013
Reviewer: Keliang Xie
Reviewer's report:
General Comments:
In this study, Liu et al shows that hydrogen enriched saline protects liver
ischemia reperfusion injury by reducing oxidative stress and HMGB1 release.
The paper is clearly written and data is convincing. However, the novelty of the
study is diminished considerably by two publications (Hayashida K, et al.
Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial
ischemia-reperfusion injury. Biochem Biophys Res Commun 2008, 373(1):30-35.;
Xie K, et al. Protective effects of hydrogen gas on murine polymicrobial sepsis
via reducing oxidative stress and HMGB1 release. Shock. 2010, 34(1):90-7.).
Additionally, the authors’ data is descriptive. In conclusion, I think, this work can
be published in this journal. But the following questions should be answered.
Major comments:
1. Normally, HMGB1 is mainly in the nucleus of cells. HMGB1 can be actively
secreted by activated macrophages or passively released from necrotic tissues.
In this study, did hydrogen enriched saline decrease the HMGB1 level through
inhibition of active secretion or passive release? In addition, how did the
hydrogen enriched saline reduce the HMGB1 levels in liver and serum?
2. In the treatment group, hydrogen enriched saline was used at a dose of 2.5, 5
or 10ml/kg. Why was the dose 3.5 ml/kg in the saline group?
Minor comments:
1. “1% hydrogen enriched saline” is not right. It should be “hydrogen enriched
saline”.
2. Page 3: HMGB1 is an early mediator of injury. HMGB1 should be a late
mediator.
3. Why was the hydrogen enriched saline used intraperitoneally not
intravenously?
4. Figure 1: Schematic illustration should be more precise. Such as, the time
points of saline administration.
5. The grouping method is not clear. In the figure legends, normal saline or
hydrogen enriched saline is used at dose of 2.5, 5 or 10 ml/kg 10 minutes before
reperfusion. But, hydrogen enriched saline is used 10 minutes before
reperfusion, and at 2, 6, 12 and 20 hours after reperfusion in grouping method.
6. The unit of Y-axis in Figure 4 is?
7. In figures, the X-axis “2h, 6, 12, 24” should be “2h, 6h, 12h, 24h”
8. The data of all groups should be offered. Such as, the data of Sham or IR
groups in figure 5.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version: 1Date:6 June 2013
Reviewer: Henri Leuvenink
Reviewer's report:
The paper is very well written and is informative. All essential information is
presented in a readable and consistent manner.
I have no major revisions but question if the research question could have been
answered using less animals. The usefulness of the 2 hours and 12 hour time
point is limited although informative.
From a technical point of view the study is performed very well and data are
presented clearly.
Minor:
Figure 4D and 4E: legend on the Y axis is missing. If 4D is the relative density
chance as measured by WB I have some concerns about the standard deviation.
The SD seems rather small. Please describe how this figure was made.
As mentioned by the authors themselves the major limitation of this study is the
IP injection used. It is unclear why this was chosen since the clinical application
is less evident. To overcome this problem, blood levels of hydrogen could have
been measured but this was also not done. Again no argumentation was given.
Finally, the comparison with other anti-oxidative drugs is marginally described.
Especially since the level of protection is significant but not complete.
For some measurements (MDA, mRNA and concentration of IL-6 and TNF)
sham levels are not given. This should be corrected since it is now impossible to
judge the level of injury or level of protection.
I also do not understand why only for HMGB1 a sham level is given. Please
explain.
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-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version: 2Date:14 October 2013
Reviewer: Min Fang
Reviewer's report:
The revised is acceptable.
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 have no financial competing interests.
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version:2Date:22 October 2013
Reviewer: Uta Dahmen
Reviewer's report:
Major comments
1. Apparently there is some confusion regarding the description of the
experimental design in terms of the dose of treatment in the control groups and
the frequency of postoperative treatment. Original manuscript, point-to-point
response and revised manuscript give different informations.
In the current version, the dose of saline in the control group was changed from
3ml/kg to 10ml/kg. Interestingly, in the point-to-point response, the dose of 5ml is
further explained.
The number of treatments with hydrogen was changed from pre- and up to four
applications postoperatively to a single application preoperatively.
Here clarification is needed.
2. Critical reassessment of the experimental design reveals that two control
groups were performed which did not add any additional insight.
The added value of an I/R group without any treatment in addition to an I/R group
treated with saline remains unclear. The sham group and the I/R was sacrificed
at 2h, which represents an early (and irrelevant) time point after injury since
injury did not yet manifest in the tested parameters. Therefore either all
observations points should have been tested or at least 12h, the time point where
highest injury would be expected and was actually observed
Further explanation regarding the selection of control groups would possibly help.
3. Substantial parts of the reviewers concerns were not addressed, but rejected,
e.g. HMGB-staining should be present in the nuclei of normal hepatocytes as
also stated by the authors. However, in their hands, normal hepatocytes
respectively sham operated animals do not present with any positive signals. The
lack of signal in the normal heptocytes deserves further attention.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version:2Date:25 October 2013
Reviewer: Keliang Xie
Reviewer's report:
The authors have made significant revisions. It is great. However, the
mechanism in this study is still unclear.
Major Compulsory Revisions
The authors should do more experiments, for example, detection of arterial and
venous hydrogen level, measurement of reactive oxygen species (ROS) in liver
tissue, why and how does hydrogen decrease HMGB1 release.
best regards
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-12 (2014)

Reviewer's report
Title:Protective effects of hydrogen enriched saline on liver ischemia reperfusion
injury by reducing oxidative stress and HMGB1 release
Version:2Date:27 October 2013
Reviewer: Henri Leuvenink
Reviewer's report:
Authors answered my questions satisfactory
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 deckare that I have nomcompeting interests
Review for 10.1186/1471-230X-14-11 (2014)

Reviewer's report
Title:Radiofrequency Ablation Following First-Line Transarterial Arterial
Chemoembolization for Patients with Unresectable Hepatocellular Carcinoma
Beyond the Milan Criteria
Version: 2Date:15 July 2013
Reviewer: Shunsuke Nojiri
Reviewer's report:
Major
The author showed the benefit combination therapy of TACE and RFA but there
were no novel data and samples were too small to discuss.
Minor
In the part of Introduction and Discussion there are a lot of same discussions. the
author should combine these parts.
There are many parts that are grammatical mistakes.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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 10.1186/1471-230X-14-11 (2014)

Reviewer's report
Title:Radiofrequency Ablation Following First-Line Transarterial Arterial
Chemoembolization for Patients with Unresectable Hepatocellular Carcinoma
Beyond the Milan Criteria
Version: 2Date:15 August 2013
Reviewer: Hiroyuki Kirikoshi
Reviewer's report:
Comments to Author
Title: Radiofrequency ablation following first-line transarterial arterial
chemoembolization for patients with unresectable hepatocellular carcinoma
beyond the Milan Criteria
Journal: BMC Gastroenterology
Type of article: Research
Authors: Lan Zhang et al.
CLASSIFICATION OF THE MANUSCRIPT
Minor Essential Revisions.
This manuscript described the combination of radiofrequency ablation (RFA) and
transarterial chemoembolization (TACE) therapy for unresectable hepatocellular
carcinoma (HCC) patients beyond the Milan Criteria. This manuscript is clearly
written and easy to read.
MAJOR COMMENTS
The procedure of combination therapy in this manuscript (RFA is performed
within 1-2 months after TACE in patients who has incomplete necrotic tumor
nodules) considered to be unique and reasonable for the effectiveness treatment.
In previous studies including our report (Hepatol Res, 2009; 39: 553-562), RFA
was performed for the all HCC lesions as possible, and performed within 1-2
weeks after TACE expecting for larger tumor necrosis due to cooling effect of
TACE.
MINOR COMMENTS
#1.
There is typos error in the title of the manuscript, “transarterial arterial###”.
#2.
Table 1, 2 and 3 are not found in this PDF file (due to error of computer or
internet?).
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-14-9 (2014)

Reviewer's report
Title:Nucleophosmin/B23 expression in gastric carcinogenesis
Version: 1Date:21 March 2013
Reviewer: Maria Piazuelo
Reviewer's report:
In this study, Leal and collaborators evaluated nucleophosmin protein expression
(by Western blot) in 17 pairs and mRNA (by qRT-PCR) in 22 pairs of gastric
tumors and corresponding non-tumor gastric tissues. They conclude that
nucleophosmin may act as a tumor suppressor in gastric carcinogenesis. The
small sample size, and the results presented do not support this conclusion.
Additional comments:
Major revisions:
1. The authors mention that the presence of H. pylori and cagA (or vacuolating
cytotoxin?, please check this) was investigated, and that all studied samples
presented H. pylori infection. It is not clear if all (neoplastic and non-neoplastic)
tissues included in the study (22 pairs) were investigated, what was the positivity
for tumor and non-tumor tissues and what were the findings on H. pylori virulence
factors.
2. It would be interesting to include immunohistochemistry studies to
demonstrate cellular and subcellular expression of nucleophosmin not only in the
tumors and non-tumoral gastric mucosa of the subjects included in this study, but
also in additional samples from subjects without history of cancer, including
normal gastric mucosa and H. pylori-associated gastritis.
Minor revisions:
3. How the cases were selected and when the tissue samples collected?
4. It would be advisable to use the most recent TNM staging classification.
5. Explain what control sample was used to normalize the protein expression by
Western blot and how the densitometry units were calculated.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-14-9 (2014)

Reviewer's report
Title:Deregulated expression of Nucleophosmin 1 in gastric cancer and its
clinicopathological implications
Version: 2Date:19 August 2013
Reviewer: Daniel P Barry
Reviewer's report:
The article has been improved by revision, but there are still two large issues in
need of correction, as well as a few typographical errors.
Major Compulsory Revisions
1. It is still unclear what is meant by “The protein level of NPM1 was reduced
1.5-fold in 35% of tumors compared to paired nonneoplastic gastric tissue.
(Abstract/Results)” What is a 1.5-fold reduction? Is it reduced 33%, 66% or
150%? Do you mean that 35% of the tumors had “at least” this much reduction?
And is the value 1.5 significant? Why not 2-fold or 10-fold? Also, what happened
in the other 65% of tumors? Was there no change, greater change, less change?
This sentence needs rewording. The mRNA sentence in Abstract/Results has
similar issues as do the corresponding sections of the Results in the main body
of the text.
In the first paragraph of the Results, the second sentence could be reworded as
such (I think) to remove confusion: “The protein level of NPM1 was reduced by at
least one-third in 35% of GC samples, and no tumor presented an increase of
more than 1.5-fold compared to their paired non-neoplastic gastric tissue (Figure
1B and 1C).” In the second paragraph of the Results, the second sentence could
be reworded: “The NPM1 mRNA level was reduced by at least one-third in 45.5%
of samples and was increased in 27.3% of samples.” In fact, everywhere the
1.5-fold reduction is mentioned, rewording as “reduction by at least one-third”
would lessen the potential for confusion.
2. The Western blots in Figure 1C must show the calibration sample as well.
Discretionary Revisions
1. Oxynctic cells could be renamed as parietal cells, the more commonly used
term.
Minor issues not for publication
1. Remove “their” from the last sentence in Abstract/Background.
2. Remove “an” from the final sentence of the fourth paragraph in the
Background.
3. In Methods/Tissue samples (first paragraph), the word “accessed” should be
changed to “assessed”. In the third paragraph, “acid nucleic” should be “nucleic
acid”.
4. In Methods/NPM1 mRNA expression by reverse transcription quantitative
polymerase chain reaction (qRT-PCR), was a non-neoplastic gastric tissue
“designed” or “designated” as a calibrator?
5. In paragraph 6 of Discussion, reword to “which suggests that a
post-translational mechanism may be involved” or “which suggests that
post-translational mechanisms may be involved” as appropriate.
6. Consistently capitalize “Western” blot / ”western” blot.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-9 (2014)

Reviewer's report
Title:Deregulated expression of Nucleophosmin 1 in gastric cancer and its
clinicopathological implications
Version: 2Date:21 August 2013
Reviewer: Maria Piazuelo
Reviewer's report:
Immunohistochemistry studies for NPM1 are incomplete and the number of
samples used is even smaller (n=12 tumors), providing unclear results. There is
no data supporting IHC evaluation in non-tumoral and/or normal gastric mucosa.
However, in Table 2, which includes only tumors, case #5 shows score for
staining in oxyntic cells.
There is no comment on the correlation between NPM1 expression by Western
blot and IHC.
Again, the authors conclude that they have “demonstrated that nucleophosmin
may act as a tumor suppressor in gastric carcinogenesis, especially in
intestinal-type GC and in tumors from patients with distant metastasis”. The small
sample size and the results presented do not support this conclusion.
Minor comment: In second paragraph of Background section it should read NO38
instead of NO28.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-9 (2014)

Reviewer's report
Title:Deregulated expression of Nucleophosmin 1 in gastric cancer and its
clinicopathological implications
Version:3Date:29 October 2013
Reviewer: Daniel P Barry
Reviewer's report:
No revisions necessary.
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