JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-14-86 (2014)

Reviewer's report
Title:Presentation, aetiology and treatment of adult intussusception in a tertiary
Sub-Saharan Hospital: a 10 year retrospective study
Version:2Date:18 December 2013
Reviewer: Antonio Martín Maya
Reviewer's report:
MAJOR REVISIONS
ALL THE PARTS OF THE MANUSCRIPT MUST BE SHORTENED. THERE
ARE SOME PARTS OF THE INTRODUCTION THAT SHOULD BE
CONSIDERED DURING THE DISCUSSION ( SOME SENTENCES OF THE
EPIDEMIOLOGY , DIAGNOSIS AND TREATMENT) , SINCE THEY ARE
ABOUT OTHER PUBLICATIONS AND RECOMMENDATIONS MAKING THE
INTRODUCTION TOO LONG.
REGARDING THE TREATMENT, THE TREATMENT IS CONFUSING IN THE
WAY THAT IT IS EXPLAINED, IS TOO LONG AND IS NOT CLEAR. WHAT IS
THE MEANING OF OPERATIVE SURGERY? I UNDERSTOOD THAT YOU
WERE TALKING ABOUT SOME TYPE OF RESECTION DURING SURGERY
(THIS MUST BE REPLACED).
ALSO YOU SHOULD EXPLAIN WHAT HAPPENED WITH THE OTHER
PATIENTS THAT THEY DID NOT HAVE RESECTION, WHAT TYPE OF
TREATMENT THEY RECEIVED?
MINOR REVISIONS
THERE IS A MISTAKE IN ONE OF THE REFERENCES DURING THE
MANUSCRIPT (INSTEAD OF THE NUMBER, THE LAST NAME OF THE
AUTHOR IS MENTIONED)
DISCRETIONARY REVISIONS
IS THE ETHNICITY DESCRIPTION IMPORTANT TO UNDERSTAND THIS
ARTICLE?, OR FOR THE TOPIC YOU ARE DEVELOPING? IF IT IS NOT
IMPORTANT MAKES THE ARTICLE CONFUSING SINCE THE PEOPLE THAT
IT IS NOT IN USE WITH THE ETHNICITY COULD THINK THIS CAN AFFECT
THE RESULTS. IF IT IS IMPORTANT I THINK YOU SHOULD EXPLAIN THE
REASON.
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-14-100 (2014)

Reviewer's report
Title:Type V pit pattern: Impact of clinical experience and magnifying
chromoendoscopy
Version:3Date:17 February 2014
Reviewer: Naoto Tamai
Reviewer's report:
This article accesses diagnostic value of magnifying endoscopy for the
experienced and non-experienced endoscopist. This article is well written and
informative, and I cannot find the vital problems for publication. Please consider
minor revision as below.
#Figure 2 is difficult to figure out; therefore the authors should avoid using
abbreviation or add more information on figure legend (CCS? MCE? ).
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-14-100 (2014)

Reviewer's report
Title:Type V pit pattern: Impact of clinical experience and magnifying
chromoendoscopy
Version:3Date:25 February 2014
Reviewer: SHiro Oka
Reviewer's report:
Comments to authors (Major Revision)
The authors presented the reliability of type V pit pattern for early colorectal
cancer to diagnose invasion depth of SM 1000µm. The collected experience is
interesting. However, there are some problems with the current study that need
to be addressed. My suggestions are as follows:
Major comments
1. This study design has a bias of conventional image to diagnose the invasion
depth using magnifying chromoendoscopy image, especially in the experienced
endoscopists. To assess the reliability of type V pit pattern, it is better to evaluate
by magnifying chromoendoscopy image alone.
2. In the selected lesions, are there any LST lesions? Especially, LST-NG
pseudodepressed type (0-IIa+IIc) with type VI pit pattern (mild irregular) has a
possibility of SM deep invasion. The authors should describe this point.
3. In this study, did the endoscopists regard type VI pit pattern (severe irregular)
as the confirmation of SM deep invasion in all cases? It is important how to
evaluate the lesions with type VI pit pattern (severe irregular), because they have
SM scanty invasion or intramucosal cancer in some cases.
4. The kappa value for intra-observer agreement of type VI pit pattern
subclassication was relatively low. The authors discuss the reason more in the
Discussion.
5. How about the kappa value for intra-observer agreement of type Vn pit
pattern? The authors should mention the results about this point.
6. How was the mean value of the SM invasion depth in the lesions deeper than
1,000µm? The interpretation is greatly different in the lesions that exceed
1000µm a little or a lot.
7. The only 1 moderately differentiated adenocarcionoma should be excluded in
this study, because the pit pattern of the moderately differentiated
adenocarcionoma often looks worse compared with that of well differentiated
adenocarcionoma.
8. In the Table 3, what is a concrete numerical value of the SM depth in the SM-d
lesions?
9. In the Figure1, I recommend that the authors should change a more typical
picture of Vn pit pattern, because the distinction between non-structure and
mucus is difficult in this case.
10. The number of references about the clinical usefulness of pit pattern
diagnosis for the colorectal lesions is relatively small. I recommended that more
references should be cited.
11. The authors had better confirm the statistical method. Mann-Whitney U test
seem to be unsuitable to analyze between 3 groups.
Minor comment
1. P6 line 5. subcategeories # subcategories
2. P6 line 7. colorectal cancers # early colorectal cancers
3. Figure2. Please describe the group (I, II or III) clearly in the figure
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 that I have no competing interests.
Review for 10.1186/1471-230X-14-100 (2014)

Reviewer's report
Title:Type V pit pattern: Impact of clinical experience and magnifying
chromoendoscopy
Version:4Date:14 May 2014
Reviewer: SHiro Oka
Reviewer's report:
It is well done of the revised manuscript, and acceptable.
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-14-84 (2014)

Reviewer's report
Title:Overall Survival in Response to Sorafenib Versus Radiotherapy in
Unresectable Hepatocellular Carcinoma with Major Portal Vein Tumor
Thrombosis: Propensity Score Analysis
Version:1Date:9 March 2014
Reviewer: Tatehiro Kagawa
Reviewer's report:
The authors compared the survival benefits of sorafenib vs. radiotherapy in
patients who had unresectable HCC with portal vein thrombosis (PVTT), and
concluded that radiotherapy was superior to sorafenib.
The evidence on the treatment regimens for advanced HCC remains insufficient.
In this regard, this paper provides important information to hepatologists.
However, there are several flaws that preclude recommendation for acceptance.
1. The authors should limit patients to Child A at the enrollment, because they did
not compare Child A and Child . Table 1 can be omitted.
2. The authors should describe about the previous treatments in more detail.
Surgery, TACE, RFA, etc. They should also mention that the patients had not
received sorafenib or radiotherapy before enrollment, if correct.
3. The number of patients with Child A who received radiotherapy was 28 in text
and Table 2, but 34 in Table 1. Which is correct?
4. The authors should describe what the values in the Tables represent. Mean or
median?
5. The word 'Main/first branch' in Tables 2 and 3 should be replaced with PVTT.
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-14-84 (2014)

Reviewer's report
Title:Overall Survival in Response to Sorafenib Versus Radiotherapy in
Unresectable Hepatocellular Carcinoma with Major Portal Vein Tumor
Thrombosis: Propensity Score Analysis
Version:1Date:20 March 2014
Reviewer: NORIO ISODA
Reviewer's report:
This is the paper reporting the survival benefits of sorafenib versus radiotherapy
(RT) in patients with unresectable hepatocellular carcinoma (HCC) and portal
vein tumor thrombosis (PVTT) in the main trunk or the first branch. It was
concluded that RT is a better first-line therapy than sorafenib in patients who
have advanced unresectable HCC with PVTT. Though there are only few studies
evaluating the factors during therapy for HCC with major portal vein tumor
thrombosis, the present study has limited number of patients with the findings of
novelty and has several concerns that need to be addressed as described
below.
Major comments:
I can not understand Figure 1.
I can not recognize a difference between (a) and (b).
Figure legends about Figure1 is vague. Does A mean a? Does B mean b?
More careful explanation is necessary.
Minor comments:
1) Page 10, line 13-15:
" the RT study population had a significant worsening hepatic function and tumor
progression in comparison with the sorafenib group".
I understand that the RT study population had a significant worsening hepatic
function, but I think tumor progression is more worsening in the sorafenib group
than the RT group, because the ratio of the main trunk to all PVTT is larger in the
sorafenib group than the RT group.
2) Page 11, line 1-2:
“We extracted 64 patients with hepatic function of C-P class A (sorafenib; n = 36,
RT; n =28), as shown in Table 2.”
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-85 (2014)

Reviewer's report
Title:Efficacy of Early Immunomodulator Therapy on the Outcomes of Crohn's
Disease
Version:5Date:25 February 2014
Reviewer: renato caviglia
Reviewer's report:
There is 1 Major Compulsory Revision:
Results: Predictive factors related to disease relapse. In this paragraph I suggest
to reanalyze the data using the normal values of erythrocyte sedimentation rate (
<15 mm#hr), C-reactive protein level (< 8 mg#L), and
hematocrit level (40.4-52%) instead of the selected cut-off points of 54, 8.1, and
37.6 (mean level of the study population) when performing the univariate analysis
to identify predictors of relapse.
Tab 2 should be re-edited according new data.
There are Minor Essential Revisions:
1) Spelling mistakes in pag 7: Results Baseline patient characteristics
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-14-85 (2014)

Reviewer's report
Title:Efficacy of Early Immunomodulator Therapy on the Outcomes of Crohn's
Disease
Version:5Date:11 March 2014
Reviewer: Pawel Kawalec
Reviewer's report:
no minor revisions in the text.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I have no competing interests to the content of the manuscript - financial nor
non-financial.
Review for 10.1186/1471-230X-14-85 (2014)

Reviewer's report
Title:Efficacy of Early Immunomodulator Therapy on the Outcomes of Crohn's
Disease
Version:7Date:6 April 2014
Reviewer: renato caviglia
Reviewer's report:
The authors fulfilled the reviewer's observations and modified the manuscript
according to them.
There are neither major or minor revisions to adopt.
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-14-82 (2014)

Reviewer's report
Title:Age-specific prevalence of serrated polyps and its subgroups by screening
colonoscopy
Version: 2Date:2 October 2013
Reviewer: Shuji Ogino
Reviewer's report:
Major compulsory revisions
This is an interesting study. Analysis methods and data are generally fine. I
request the authors to quote following references to further discuss important
points:
1. Rex D, et al. Am J Gastroenterol 2012 (expert recommendations on serrated
lesions. First, terminology – serrated polyps should not be used)
2. Yamauchi M, et al. Gut 2012 (This study showed a continuum of molecular
changes (CIMP, MSI, BRAF mutation) from rectum to ascending colon. This
study has big impact on gastroenterology, because of the prevalent dogma of
proximal vs. distal dichotomy, which is clearly oversimplification.)
3. Yamauchi M, et al. Gut 2012 (this is a review and presents discussion of the
colorectal continuum model)
4. Nishihara R, et al. N Engl J Med 2013 (recent study showed long-term effect of
colonoscopy in population-based cohort studies. This also showed that
CIMP-high cancer which arises from serrated lesions is more difficult to prevent,
than non-CIMP-high cancer.)
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-14-82 (2014)

Reviewer's report
Title:Age-specific prevalence of serrated polyps and its subgroups by screening
colonoscopy
Version:2Date:10 November 2013
Reviewer: Leticia Moreira
Reviewer's report:
Age-specific prevalence of serrated polyps and its subgroups by screening
colonoscopy
This study analyzes the prevalence of serrated polyps in a large cohort of
asymptomatic subjects, stratifying this prevalence by age.
In general, the study is well done, and includes more than 28,000 subjects,
although I have some comments:
Minor comments:
1) In the introduction, the authors describe sessile and also traditional serrated
adenomas as flat or sessile, poorly demarcated lesions, although literature
describe traditional serrated polyps mainly as pedunculated lesions.
2) Discussion should be modified; it is more a description of other studies, rather
than a discussion of this manuscript. Please comment the strengths and
limitations of the study.
Major comments:
1) First of all, the authors should review the language; there are many mistakes
in redaction that make reading difficult, mainly in the introduction.
2) Aim of the study is not well correlated with the conclusions. Please modify it.
3) I am concern about including patients of 20´s and 80´s years old
(asymptomatic patients? check-up?, do young people have relatives with
colorectal cancer). Please clarify this point.
4) Serrated polyposis syndrome was diagnosed? How many?
5) Authors should include p-values in the % comparing ADR (table 2 and 3), as
well as p-value comparing different ages (table 4), measuring the real difference
between young and old people.
6) Please clarify the association between colorectal cancer and serrated
polyps.To arrive to that conclusion, authors should analyze the prevalence of
serrated polyps by age, and also by type of serrated polyp (sessile, hiperplastic,
traditional), and size (< or > 10 mm). For example, do younger patients have
more hiperplastic polyps at the rectum of <5 mm of diameter?, so it is not
necessary a endoscopic surveillance. If authours will recommend in the
conclusion endoscopic screening before age 50, should justify that this risk is not
given only for small hiperplastic polyps in the rectum, which have no malignant
potential. Please clarify this important point.
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-14-82 (2014)

Reviewer's report
Title:Age-specific prevalence of serrated lesions and its subtypes by screening
colonoscopy
Version:3Date:13 January 2014
Reviewer: Leticia Moreira
Reviewer's report:
Thanks for kindly respond to my suggestions, I think the article has improved
significantly with the changes.
No further comment.
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 do not have financial competing interests.
Review for 10.1186/1471-230X-14-83 (2014)

Reviewer's report
Title:Clinical predictors of incident gallstone disease in a Chinese population in
Taipei, Taiwan
Version: 2Date:29 August 2013
Reviewer: Tom Bates
Reviewer's report:
Most of the findings of this careful long term study are unsurprising but the
documentation of the incidence (rather than the prevalence) of gallstone disease
(GSD) in a Chinese population, albeit in Taiwan, is important.
1. There are very few studies of the incidence of GSD and it is of interest that the
prevalence (c 5%) and the incidence (c 0.6% pa.) differ very little from two Italian
studies, 10 years apart - GREPCO (1998) and MICOH (2008). This may suggest
that the diet of the Chinese in Taiwan is already Westernised.
2. The references (p8) "was slightly lower than other evidence-based studies
[2,9]" should read [2,10].
3. It is unfortunate that the proportion of the population lost to follow up was in
the higher risk categories for GSD. This deficiency is likely to have under
recorded the overall incidence but this is clearly documented and acknowledged.
However Table 1 indicates that the older population had a higher attendance rate
which requires some explanation.
4. This sample of the population was probably unrepresentative in addition to the
stated self-selected hospital-based patients, in that those aged 60 or over were
only 18% of the sample and yet developed 48% of the gallstones.
5. The statement (p9) "that the findings show that females do not have a
significantly higher incidence of all types of GSD than males" is almost certainly a
Type II error due to small numbers, since the Relative Risk is 2.1.
6. The manuscript is well written although there are occasional phrases the
meaning of which is uncertain.
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-14-83 (2014)

Reviewer's report
Title:Clinical predictors of incident gallstone disease in a Chinese population in
Taipei, Taiwan
Version: 2Date:2 September 2013
Reviewer: davide festi
Reviewer's report:
Major compulsory revisions.
The study of Liu et al deals with an important clinical problem, i.e. gallstone
incidence. Several methodological problems are present in the sudy, some of
them are identified by the Authors in the last part of the manuscript.
a) it is not clear how the subjects were enrolled: were the subjects prospectically
enrolled?what was the inclusion criteria?
b) the attendance rate is too low (57.3%) to allow conclusions regarding gallstone
incidence. It would be necessary to have information (presence or absence of
gllstones, history of cholecystectomy) also on subjects who did not participate to
the follow-up (using for example telephone interview).
c) there are no data regarding the clinical picture of gallstones (the percentage of
symptomatic gallstones; the reason for cholecystectomy, etc.)
d) gallstone incidence was higher (although non significant) in female; howver
there are no data regarding the number of pregnancies and the frequency of pill
use.
e) it is well know that dieting is a risk factor for gallstone; no data are present in
the study
f) since all the enrolled subjects underwent ultrasonographic evaluation of the
upper abdomen, information on the frequency of liver steatosis should be useful,
also for better define the result concerning ALT
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 interest's below.
Review for 10.1186/1471-230X-14-83 (2014)

Reviewer's report
Title:Clinical predictors of incident gallstone disease in a Chinese population in
Taipei, Taiwan
Version:3Date:1 April 2014
Reviewer: Tom Bates
Reviewer's report:
Minor Essential Revision: The authors have responded to the comments of both
referees as far as they are able and they have carried a telephone survey of the
non-attenders. I think that the results of this survey should be included in the
Methods and Results sections rather that appended to the Discussion. It is noted
that 12/964 developed symptomatic gallstone disease (1.2%) over 5+ years
compared with 1.8% of the attenders over a mean of 3.5 years, albeit not all
symptomatic. This is worthy of comment.
The final Conclusion (p12) should avoid abbreviations.
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-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version: 3Date:8 October 2013
Reviewer: Begoña Ochoa
Reviewer's report:
Given that few studies have reported increased circulating levels of oxidative
stress markers in patients with non-alcoholic fatty liver and no published study
has been performed with newer markers of systemic oxidative stress, the authors
aim to assess the relationship between urinary 8-iso-prostaglandin F2# , a well
admited marker of oxidative stress, and serum soluble NOX2-derived peptide
(sNOX2-dp) and the severity of liver steatosis in subjects with non-alcoholic fatty
liver. Overall, the study is designed and performed appropriately, including an
ample cohort of patients, although it elicits the drawbacks that the authors
themselves point out in the Discussion section. In summary, the study
demonstrates that the levels of urinary 8-iso-PGF2# were independent predictors
of non-alcoholic fatty liver
and a strong association of urinary 8-iso-PGF2# and of serum sNOX2-dp with
the severity of steatosis at ultrasound was also observed. These findings are
interesting and valid in clinical practice.
Minor essential revisions:
The authors conclude "We demonstrated an increased NOX2-generated
oxidative stress in subjects with non-alcoholic fatty liver. Oxidative stress was
independent from obesity, diabetes and metabolic syndrome and increased with
the severity of liver steatosis at ultrasound." None of the sentences is right.
Serum oxidative stress markers are general markers of the oxidant-antioxidant
balance of the whole body and no measurement of free radicals derived from
NOX2 has been performed. Neither "such oxidative stress" can be said that is
independent of the conditions alluded. Therefore, conclusions should be rewritten
properly.
Although the authors report that subjects underwent routine biochemical
evaluation, they should clearly state how urine and blood collection and
treatment was performed, otherwise experimental conditions may be not
reproducible.
Tables. Parameters should be clearly defined in footnotes in all tables. Revise
commas and dots.
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 no competing interest.
Review for 10.1186/1471-230X-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version:3Date:28 November 2013
Reviewer: Amedeo Lonardo
Reviewer's report:
1.The “two-hit theory”, although aften quoted, is not the only nor the most
updated one. Other pathogenic and histogenic views have been proposed and
may be discussed ( Wanless IR, Semin Liver Dis.2004;24:99-106; Lonardo A, et
al. Clinical physiology of NAFLD: a critical overview of pathogenesis and
treatment Expert Review of Endocrinology and metabolism 2010 ; Tilg H,
Hepatology. 2010;52:1836-46.). In particular, the Authors may be willing to
discusss that simple steatosis and NASH are probably two unrelated disorders (
Lonardo A, et al. Expert Rev Gastroenterol Hepatol. 2011;5:135-9. Yilmaz Y.
Aliment Pharmacol Ther. 2012;36:815-23.)
2.The Authors may be willing to discuss that, at variance with other more recent
and validated indices (Ballestri S, et al Liver Int. 2012;32:1242-52.). the
ultrasonographic Hamaguchi score does not specifically predict NASH.
3.The Authors need to be more prudent: Statistical association between US
evidence compatible with steatosis and markers of increased oxydative stress
does not imply casuality. Moreover, the two quoted studies (Pacana T, Curr Opin
Clin Nutr Metab Care 2012,15:641–648. and Sanyal AJ, New Engl J Med
2010,362:1675–1685.) are not guidelines. Finally, based on comparative
analysis, the statement that guidelines support antioxidant treatment should be
deleted (Nascimbeni F, J Hepatol. 2013;59:859-71.).
4.This submission states that “Liver steatosis was defined according to
Hamaguchi criteria based on the presence of abnormally intense, high level
echoes arising from the hepatic parenchyma, liver-kidney difference in echo
amplitude, echo penetration into deep portion of the liver and clarity of liver blood
vessel structure [32-33].” Accordinlgy, reference 32 needs to be deleted.
5.The statement “.....ultrasound, which is a qualitative method inadequate to
quantify less than 30% liver fat content [36].” conflicts with more recent studies
(Dasarathy S, J Hepatol. 2009;51:1061-7).
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 that I have no competing interests'
Review for 10.1186/1471-230X-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version:3Date:16 December 2013
Reviewer: Carmine Finelli
Reviewer's report:
Major Compulsory Revisions
• What is the concentration of 8-iso-prostaglandin F2# (8-iso-PGF2#) in patients
with NAFLD without METS?
• Are patients smoking?
• What is the renal function of patients?!
In fact, the prostaglandin, 8-iso-PGF2#, is an isoprostane that is produced by the
non-enzymatic peroxidation of arachidonic acid in membrane phospholipids.
Measurement of 8-iso-PGF2# is a reliable tool for the identification of subjects
with enhanced rates of lipid peroxidation. Enhanced formation of 8-iso- PGF2#
has been reported in association with several cardiovascu¬lar risk factors, as
well as atherosclerosis. Cigarette smoking is a risk factor for renal function
alteration in healthy smokers and is characterized by a high eGFR and a high
urinary protein associated with an increase in the 8-iso- PGF2# and hs-CRP.
(Sauriasari R, Sakano N, Wang DH, Takaki J, Takemoto K, Wang B, Sugiyama
H, Sato Y, Takigawa T, Takahashi N, Kanbara S, Hitomi Y, Nakamura H, Ogino
K. C-reactive protein is associated with cigarette smoking-induced hyperfiltration
and proteinuria in an apparently healthy population. Hypertens Res. 2010 Nov;
33 (11): 1129-36.)
Patients with NAFLD have almost all damage endothelial (dysfunction). This
damage is known to be correlated with elevated concentrations of 8-iso-PGF2#
(Nassar H, Furukado S, Tanaka M, Miwa K, Okazaki S, Sakaguchi M, Mochizuki
H, Kitagawa K. The relation between carotid plaque echogenicity and oxidative
stress marker 8-iso-prostaglandin F2#. Ultrasound Med Biol. 2012
Mar;38(3):487-91.). Should it be evaluated perhaps?!
In addition, lacking a healthy control group !!!
Minor Essential Revisions
The interpretation (discussion and conclusion) should be reevaluated in the light
of these results, as well as any statistical analysis.
Tables are not easily accessible to the reader and should be semplicate and
divided.
Discretionary Revisions
• Why the authors not describe patients without METS?
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-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version:3Date:20 December 2013
Reviewer: Sven Francque
Reviewer's report:
Major Compulsory Revisions
The authors report on the parameters of oxidative stress in patients with NAFLD.
The question is relevant. The paper is well written and nice to read. Methodology
is overall well-elaborated and adequate.
Some issues need to be addressed:
According to the correlation table, the urinary PGF2alpha strongly correlates with
BMI and inversely with adiponectin, but to a lesser extent with the US Hamaguchi
score. In the regression analysis looking at the dichotomous question NAFLD vs.
no NAFLD, BMI appears not to be an independent variable.
This asks for some comments:
First NAFLD is not always NASH, and in terms of inflammation and disease,
NASH is considered more dangerous than simple steatosis. The question is
whether we expect oxidative stress to be increased in a patient with mild
steatosis and without steatohepatitis. So the question remains whether we want
to oppose NAFLD vs. no NAFLD (which means that mild degrees of steatosis are
also included) or whether the relationship with the severity of the steatosis is
more relevant. So I would like to see a regression analysis assessing factors
independently related to the severity of the NAFLD, and a regression analysis
assessing factors independently related to the degree of oxidative stress as
based on the parameters used in this paper.
Furthermore non-invasive scores for the diagnosis and severity of NASH and
fibrosis. Most of these scores can be calculated with the parameters that were
recorded in these patients. I would therefore like to see an analysis in relation to
these scores, and a comparison nash vs. no nash (it can be argued that, as there
is no biopsy as golden standard, these scores can be used (with all their inherent
limitations)).
It would also be nice to include waist in the analyses, as visceral obesity seems
to be more relevant than just the BMI.
The question remains unanswered, as this is a cross-sectional analysis (this
should clearly be discussed by the authors) whether oxidative stress, caused by
obesity, contributes to the pathophysiology of NAFLD (or perhaps more NASH)
or whether the inflamed liver contributes to the oxidative stress (and hence long
term complications).
Discretionary Revisions
A minor remark: overall the paper is very well written, but some of the tables
need some correction (cytocheratin 18 e.g.).
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-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version:4Date:5 March 2014
Reviewer: Amedeo Lonardo
Reviewer's report:
The Authors have satisfactorily addressed all the issue raised by this Reviewer.
Therefore, I would recommend the publication of their submission.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests'
Review for 10.1186/1471-230X-14-81 (2014)

Reviewer's report
Title:NOX2-generated oxidative stress is associated with severity of ultrasound
liver steatosis in patients with non-alcoholic fatty liver disease
Version:4Date:14 March 2014
Reviewer: Carmine Finelli
Reviewer's report:
I think that the authors have greatly improved the paper by responding
adequately to all comments suggested by reviewers.
Therefore, the paper can be accepted without further revisions.
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-14-80 (2014)

Reviewer's report
Title:Long-term efficacy of infliximab for refractory ulcerative colitis: Results from
a single center experience
Version:2Date:12 January 2014
Reviewer: Krisztina Gecse
Reviewer's report:
Major Comments
1. It is methodologically questionable to include the patients in the study who only
received one single dose of anti-TNF and were followed-up for several years to
assess the long-term efficacy of infliximab. Furthermore, more than half of these
patients were “non-responders” to an IFX single dose, thus received tacrolimus
during follow-up and the colectomy-free rate was calculated at 87 months.
Therefore, I would strongly recommend excluding the patients from the study that
received one single those of IFX.
Minor Comments
1. The number of patients included in the study is rather small for a 10-year
period, altogether 31 patients completed induction treatment with IFX. Providing
a sentence about anti-TNF regulations in Japan would be useful.
2. Please provide details about the duration of IFX maintanence treatment and
about the timing of relapse in the 17 responders that received dose
intensification.
3. English language needs refinement, e.g.: colon cancer instead of colitic
cancer; ‘thiopurine agents’ require the use of plural on Page 5; please rephrase
sentence on Page 18, Line 7, etc.
4. Reference list needs refinement, e.g.: Page 4, Line 12, sentence refers to the
ACT trial, which does not match the reference; Page 4, Line 9 reference missing;
etc..
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 have receives speakers' honoraria from MSD.
Review for 10.1186/1471-230X-14-80 (2014)

Reviewer's report
Title:Long-term efficacy of infliximab for refractory ulcerative colitis: Results from
a single center experience
Version:2Date:31 January 2014
Reviewer: Gionata Fiorino
Reviewer's report:
The Authors reported the results from a retrospective cohort of patients treated
with infliximab for refractory ulcerative colitis, followed up on the long-term. They
found that about half of subjects required dose intensification with a very high
colectomy-free rate on the long-term. They also tried to investigate possible
predictors for long-term remission after dose intensification.
The topic is of high interest, since data on the efficacy of dose intensification of
infliximab over 12 months are not available. The manuscript is well written, but
can be improved in terms of clarity. Some issues should be addressed to the
Authors to make the manuscript suitable for publication.
1) The Authors evaluated different endpoints in their cohort. While the primary
endoint is clear, the secondary endpoints declared in the "Assessment" section
are not all consistent with the reported results. I suggest the Authors to detail all
the endpoints in the Results section, following the same outline they used in the
list of endpoints cited in the "Assessment" section.
2) The timeline of the study is quite hard to understand. There are different
endpoints reported for different follow-up time. In particular, the time to colectomy
is not clear in the Results section (it seems 63 months on average), as well as
the other endpoint time-to-observation. Please consider to calculate all the
endpoints at a definite timepoint (i.e. 3 or 5 years). Otherwise, specify the time of
observation for all the endpoints throughout the manuscript.
3) I suggest to discuss the results considering also the data from Cesarini et al.
2013, which investigated a similar cohort of patients with similar endpoints on the
short-term.
4) The discussion on the role of previous CMV infection should be improved. In
the Results section, details on how previous CMV positivity could affect the
therapy with infliximab are not provided. I suggest to add a brief section on this
aspect, also explaining how the Authors differentiated a CMV-related colitis from
a non significant CMV-overinfection.
5) The references need to be edited as required by the Journal guidelines.
Please check also all the lists of Authors, as some are not correct (i.e. ref. 19).
6) Figure (1): There is a mispelling on Tacrolimus. Please correct.
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-14-79 (2014)

Reviewer's report
Title:Biomarkers can predict potential clinical responders to DIMS0150 a
Toll-Like Receptor 9 agonist in ulcerative colitis patients
Version:2Date:17 February 2014
Reviewer: mojgan mohammadi
Reviewer's report:
The authors of the study have analyzed potential clinical responders to
DIMS0150 in UC patients. The study is well designed, written and performed. In
over all the study provides
interesting information with regard to possible role of TLR-9 agonist namely
DIMS0150 in steroid refractory UC patients.
Overall, this manuscript needs some revisions:
• Methods of abstract don’t present any explanation about methods' section of
manuscript.
• I recommend the authors to minimize the introduction because it is too long.
• In Blood collection and PBMC isolation and stimulation section of manuscript,
Authors have mentioned that "cell stimulated for 48hrs with 4 DIMS0150 (25µM
or 100µM) in the presence or absence of Dexamethasone (10 -6, 10-8, 10-10
M)". There is not any explanation about why researchers have specifically
chosen Dexamethasone from various other glucocorticosteroid? Additionally,
there is not any explanation about why they employed Dexamethasone in the
specific concentration such as 10 -6, 10-8, 10-10 M in the cell culture assay?
• There are not any details about method of data analysis for SYBRGreen qPCR.
For example did authors employ 2-##CT method for studying of mRNA
expression? The authors should explain about that.
• In a good design qPCR study, a panel of candidate house- keeping genes
should be chosen and tested by real-time RT-PCR to make sure about absence
of fluctuation in the gene expression before employing them as a reference gene.
Authors must declare their data regarding to constant expression of #-actin in
stimulated and non-stimulated PBMCs, otherwise they are not eligible to use this
gene for normalization in their gene expression assay.
• Recent studies implicated that TLR9 (#1237T/C) polymorphism has influence in
the development of IBD. I think authors should consider the importance of steroid
refractory UC patients' genotype for TLR9 (#1237T/C) polymorphism to make
sure about their interpretations before any further clinical trials.
• Additionally, I found MDR-1 gene in table 3 of the manuscript, as List of steroid
response genes screened in biomarker assay. As far as I know, there are many
reports about association of MDR-1 gene polymorphisms with UC in different
ethnic groups. If it is possible, I recommend the authors to determine steroid
refractory UC patients' genotype for C3435T MDR-1 polymorphism to make sure
about influence of genetic variations in response to DIMS0150.
Review for 10.1186/1471-230X-14-77 (2014)

Reviewer's report
Title:Correlation between depression, anxiety, and polymorphonuclear cells'
resilience in ulcerative colitis. The mediating role of heat shock protein 70.
Version: 2Date:27 July 2013
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
I appreciate the authors considering my previous comments and making
changes. However, while they have provided responses to the questions raised, I
find that several of my concerns remain unaddressed. The major ones that
persist are listed below.
1. Please check the numbering of your citations. The first listed citation is
numbered 31.
2. I am not sure I understand the rationale for the dichotomous HsP70 category
between the PMN’s and the other tissue sites. It seems like this decision on HsP
classification (as positive or negative) was made a posteriori, after the data was
available and analyzed. I would favor using a consistent scoring pattern across
all tissue sites as there is no biological reason to use different strata.
3. The lack of information on medication use at the time of HsP measurement is
also an important limitation. Even if this parameter did not influence HsP
expression, this data should be available to the authors and included in the
manuscript.
4. I am not sure I agree with the author’s rationale of only a bivariate analysis
between depression/anxiety state and HSP expression, particularly if all the
patients had psychometric scores within the range of normal values as
suggested by the authors. Please adjust for biologically relevant variables (age,
sex, disease activity, treatment) – or at the very least, show that the above
variables do not correlate with HSP status. Otherwise, there is a strong possibility
of confounding.
5. I also continue to be concerned about the likelihood of false discovery given
the lack of a clear hypothesis and the number of comparisons being made with
the multiple psychometric scales and biopsy sites. Please provide a strong
rationale for why false discovery is not an issue.
6. Overall the manuscript remains quite hard to follow and doesn’t clearly flow
from the results to the conclusions and subsequent implications.
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-14-77 (2014)

Reviewer's report
Title:Correlation between depression, anxiety, and polymorphonuclear cells'
resilience in ulcerative colitis. The mediating role of heat shock protein 70.
Version: 2Date:21 August 2013
Reviewer: Eva Szigethy
Reviewer's report:
The authors did an admirable job in addressing the critiques and I have no
additional suggestions.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
None
Review for 10.1186/1471-230X-14-77 (2014)

Reviewer's report
Title:Correlation between depression, anxiety, and polymorphonuclear cells'
resilience in ulcerative colitis. The mediating role of heat shock protein 70.
Version:3Date:17 February 2014
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
My concerns have mainly been addressed. I remain concerned about the
likelihood of false positives given multiple comparisons, and some a posteriori
assumptions the authors make (like dichotomous HsP70 status).
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-14-76 (2014)

Reviewer's report
Title:Factors Associated with Mortality Risk for Malignant Colonic Obstruction in
Elderly Patients
Version:1Date:7 December 2013
Reviewer: Renumathy Dhanasekaran
Reviewer's report:
Minor revisions
1. In the last line of the results section of the abstract, there needs to be a space
between overall and 30-da.
2. Discussion can be shortened and made more succinct.
3. Tables 4A and 4B can be merged and the multivariate analysis results added
as a separate column in univariate analysis. For several variables the p value is
mentioned as 0. Please explain. If no significance is found, consider writing ‘ns’.
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.