JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-021-01838-x (2021)

Title: Development and Validation of a New Algorithm Model for Differential Diagnosis
Between Crohn's Disease and Intestinal Tuberculosis: A Combination of Laboratory, Imaging
and Endoscopic Characteristics
Version: 1 Date: 16 Mar 2021
Reviewer's report:
Thank you for inviting me to review the manuscript "Development and Validation of a
New Algorithm Model for Differential Diagnosis Between Crohn's Disease and Intestinal
Tuberculosis: A Combination of Laboratory, Imaging, and Endoscopic Characteristics."
This issue is always a problem for a physician in clinical practice to differentiate between them.
However, the previous and recent study was already published with a more significant number
of patients. I would like to discuss some of my points of view and comment as follows.
1. The author should beware of starting the diagnostic algorithm due to the IGRA due to its
result depend on the cut-off level. Unfortunately, it was frequently showed the indeterminate
consequence, which the purposing algorithm might not work.
2. The study did not provide the ROC for the sensitivity analysis
3. The mentioned CART is challenging to follow, but it relatively seems to show the probability
of ITB and CD.
4. For the validation of the diagnostic test, the authors should beware that the validating group
has the same background and same diagnosis method (internal validation). The authors should
underline this limitation.
5. As for the ITB diagnosis, the author should provide the numbers of a patient who responded
to ATT. How many percent of the patient had disappeared from ulcerations on endoscopic
examination, and how long the patients were in the follow-up.
Abstract
The conclusion should provide the essential or significant findings of the study. Please consider
revising the conclusion part.
Introduction
This study should review the background of previously published reports in differentiation
between ITB and CD. What are the characteristic endoscopy, labs, and imaging for
differentiation of ITB and CD
Method
The author should provide the method and information of T-SPOT.
Results
The author should provide specific data of what is group 1 and group 2. (It was confusing)
In validated patients who misdiagnose between ITB and CD, the authors should provide these
patients' data.
Table
Columns group 1 and group 2 should be labeled as ITB or CD.
Review for 10.1186/s12876-021-01838-x (2021)

Title: Development and Validation of a New Algorithm Model for Differential Diagnosis
Between Crohn's Disease and Intestinal Tuberculosis: A Combination of Laboratory, Imaging
and Endoscopic Characteristics
Version: 1 Date: 18 Mar 2021
Reviewer:  José María Paredes
Reviewer's report:
Interesting and practical work by Ly Y et al. However, several considerations are necessary for
it to be accepted for publication.
Major considerations:
a) It should explain how the endoscopic and radiological variables have been selected. For
example: why do they consider 4 or more segments affected?
b) A better description of the locations affected by both diseases should be made in the endoscopy
and in the imaging techniques.
c) The results must be reviewed. If p <0.05 is considered significant, there is an error in the
comparison of the pathological variables
Minor Considerations:
a) The ITB and CD groups must be maintained throughout the text and the tables. Avoid calling
them differently (Groups 1 and 2).
b) At the beginning of the work, it should be defined that T-SPOT is a trademark for the detection
of the release of interferon Gamma. Remove it from the discussion.
c) The flow of patients and their selection should be explained in detail. Personally, I do not
understand where this sentence comes from: "One hundred and sixty-eight and forty-four cases
were allocated to the training cohort and validation cohort, respectively".
d) Table 6 should be revised and should define the acronyms.
Review for 10.1186/s12876-021-01838-x (2021)

Title: Development and Validation of a New Algorithm Model for Differential Diagnosis
Between Crohn's Disease and Intestinal Tuberculosis: A Combination of Laboratory, Imaging
and Endoscopic Characteristics
Version: 1 Date: 22 Mar 2021
Reviewer's report:
This is an interesting article which aim is to demonstrate the construction of a simple and novel
algorithm that could be useful in clinical practice about the differential diagnosis between CD
and ITB, mainly in developing countries where there are a great incidence and prevalence of
ITB  and also a growing prevalence of CD However, I have some suggestions :
1- Revision of table 6 it will be necessary to demonstrate the significance of the employed
abbreviatures
2- Revision of some English errors as visualized in table 2 / table 3:  “not all patients had these
results”
3-  A better definition of the exclusion parameter: the result of T-SPOT or endoscopic characters
or CTE/MRE was not complete,
Review for 10.1186/s12876-021-01838-x (2021)

Title: Development and Validation of a New Algorithm Model for Differential Diagnosis
Between Crohn's Disease and Intestinal Tuberculosis: A Combination of Laboratory, Imaging
and Endoscopic Characteristics
Version: 3 Date: 15 Apr 2021
Reviewer:  José María Paredes
Reviewer's report:
After the modifications made by the authors, the manuscript has improved. However, the
association of the variables discussed in the introduction should be better explained: "For
imaging characteristics, target sign, comb sign, adipose creeping sign and involvement of fewer
than 4 segments were reported to be vital parameter [8, 9, 11-13]. For endoscopic parameters,
longitudinal ulcers, transverse ulcers, aphthous ulcers, cobblestone, and stricture were proved to
be useful. " Table 6 is still not well defined; What do the numbers indicate? Number of patients
or percentages.
Review for 10.1186/s12876-021-01865-8 (2021)

Title: Normal values for high-resolution anorectal manometry in healthy young adults: Evidence
from Vietnam
Version: 1 Date: 05 Apr 2021
Reviewer's report:
This study establishes normal values of HRAM in young healthy adults in Vietnam, and in
particular, examine the influence of sex on various outcomes. The Design of case studies
is statistically sounding. The Method/Results are fairly explained. The Discussion are well
conducted, including comparison with literature and reasoning from physiology. The limitation
on sample size and constraint of single center is also well addressed.
I have two recommendations for a minor revision.
1) Method section: It is helpful to clearly explain how to derive/calculate below outcomes
from HRAM:  maximum resting pressure, maximum squeezing pressure, maximum coughing
pressure, and maximum strain pressure values. Optionally, one can cite related literature that
gives details on those calculations.
2) Result section: As HRMA consists of eight-channel sensors, illustration on (temporal-)spatial
variations among those 8-channel pressure data could provide more physiological information.
Hence, two pressure figure/topography, one for a male and the other for a female subject, may
help the reader to appreciate the difference.
Review for 10.1186/s12876-021-01865-8 (2021)

Title: Normal values for high-resolution anorectal manometry in healthy young adults: Evidence
from Vietnam
Version: 1 Date: 26 Apr 2021
Reviewer's report:
This Manuscript provides normal values in 30 healthy volunteers for the isolab manometry
system.
Methods: the catheter design should be explained more in detailed as sensor design affects
measurements. Which manometry protocol was used? Was the London classification applied
for analysis of results?
Discussion:
an extensive revision is recommended. While the main limitation of the small sample size -
although a power calculation is provided - is briefly discussed , neither the impact of catheter
and sensor design, age , gender and parity are. one paragraph should discuss the measuremnts
obtained in the light of other normal values published. With regards to sensation measuerments
impact of equipment and distension protocol were not discussed sufficiently.
Review for 10.1186/s12876-021-01870-x (2021)

Title: Assessing prognostic value of early tumor shrinkage and depth of response in first-line
therapy for patients with advanced unresectable pancreatic cancer
Version: 3 Date: 07 May 2021
Reviewer's report:
Dr. Yang and his colleagues here described that early tumor shrinkage of the response (ETS) and
depth of response (DpR) are prognostic factors. I found some original papers which investigated
the relationship ETS and prognosis as well as DpR in patients advanced pancreatic cancer. This
is all reason why the paper doesn’t have any value.
1) Vivaldi C et al. Cancers (Basel) 2019; 4: 939.
2) Kaga et al. Oncotarget 2016; 7: 67314-67320.
3) Takano N et al. Surgery Today 2021.
Review for 10.1186/s12876-021-01870-x (2021)

Title: Assessing prognostic value of early tumor shrinkage and depth of response in first-line
therapy for patients with advanced unresectable pancreatic cancer
Version: 3 Date: 21 May 2021
Reviewer's report:
This manuscript demonstrated the impact of ETS and DpR on the outcome of unresectable
pancreatic cancer patients. I reviewed this manuscript with interest, and I think that the results
are clearly presented. However, I am concerned about some points as below. This paper could
be more informative if the following were addressed.
1. In Table 1, as for histology, 65 patients of enrolled 90 patients were classified as
“unclassified”. The author describes that the enrolled patients had histopathologically confirmed
RMPC in page 5. Among pancreatic cancer, unclassified cancer is not generally major, and
therefore, I think the part of “unclassified” in this report might be too much. The author must
show the reason.
2. In this report, 15 regimens were included, and number of almost them were very small.
Caterina V et al reported the effect of ETS and DpR on the outcome was dependent on the first-
line regimen, FOLFOXIRI or G+Nab-paclitaxel. Was there some difference among regimens in
this research? Please discuss the difference of the effect based on the regimen.
Review for 10.1186/s12876-021-01870-x (2021)

Title: Assessing prognostic value of early tumor shrinkage and depth of response in first-line
therapy for patients with advanced unresectable pancreatic cancer
Version: 3 Date: 31 May 2021
Reviewer:  Federica Rubbino
Reviewer's report:
Some small tricks can improve the quality of the paper and its accuracy
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 01 Feb 2021
Reviewer's report:
Comments to the Author
This bioinformatical research classified patients with GIAD into TGF-# high/low subtypes
using gene expression status of TGF-# signaling and analyzed the differences in multi-omics
between the two subtypes. Moreover, some anticancer drugs that target the genes with different
expression between the two subtypes were identified using the public database of cancer
cell lines. I agree that this study provides some essential information about the molecular
characteristics of TGF-# high/low subtypes in GIAD. However, in publishing this article in BMC
Gastroenterology, I have a few problems and questions as follows.
1. The abstract of this manuscript lacks the Methods section. This does not seem to fulfill the
criteria of BMC Gastroenterology.
2. Why does the trend of mRNA expression differences not match that of protein expression
differences in Figure 2?
3. I recommend describing why gene amplifications and deletions were more common in the
TGF-# low group, especially in STAD.
4. This research showed dabrafenib, a mutant BRAF-V600 specific inhibitor, can target multiple
oncogenes with different expression associated with TGF-#. You might want to describe your
ideas or to refer to previous reports on the relationship between BRAF-V600 inhibitor in the
article.
5. I suppose that “drug resistant drug” in the abstract and “Exprssion” in Figure 5e are typo. You
might also want to clarify which types of GIAD are shown in Figure S1, B to E.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 24 Feb 2021
Reviewer's report:
The manuscript entitled ‘‘Characterization of TGF# -associated molecular features and drug
responses in gastrointestinal adenocarcinoma’’ by Zhang et al.  provide a comprehensive
analysis of the TGF# superfamily molecules in GIAD. The topic is interesting since TGF#
plays an important role in tumor progression, and it trigger us to know more about the TGF#
superfamily signature in the progression and treatment of GIAD. The finding is also important as
it analyzed the TGF# signature in different types of GIAD, and predicted some anti-tumor drugs
which might be useful in the therapy. However, several descriptions and interpretations for their
finding are not accurate and unclear in the text.  I suggest the text be revised as following
1. TGF# superfamily or TGF#-related molecules is not TGF#,  t.ex. line 29 in Abstract ‘‘
the molecular characterization of TGF# in GIAD’’ is not accurate. There are several similar
description in the text, and need to be carefully revised.
2. These is no methods in the Abstract, and good to have it to understand the results.
3.  The conclusions in the Abstract in line 39 are not accurate according to the findings in the
paper.
4. Line 50    Should be ‘‘all types of GIADs share the same features’’
5. Which method is used to select the significant gene mutation?
6. Line322   Top 10 genes used in DNN model are the first top 10 genes in Figure 3a? if not,
should describe them in the text.
7. Line 350-351   miRNAs and mRNAs are interpretated in an opposite way?
8. Discussion in Line 357,  ‘‘ Several drugs suggested a great sensitivity to TGF#‘‘,  what are
these drugs and their target should be discussed, since they are findings in this paper.
Similarly in Line 358 , ‘‘ some classic oncogenes were found to be targeted‘‘, what are those
oncogenes should be discussed.
9.  Line367,   The description ‘‘ with inhibiting proteins downregulated‘‘ is unclear, what are
these inhibiting
proteins?
9. Line 371,  abbreviation  ‘‘ SCNA ’’ was not described in the text.
10. Line 372-376  ‘‘which might produce more neoantigen that can be targeted at’’ is not
accurately interpreted and the following discussion about TGF#low is  unclear.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 25 Feb 2021
Reviewer:  Genwen Chen
Reviewer's report:
The study by Zhang et al. analyzed the TGF#-associated molecular features in GIAD. They
revealed comprehensive networks of TGF#-associated mRNAs, miRNAs, and proteins. Overall,
the manuscript is well organized but with little novelty, because the TGFb pathway was well-
known and widely studied. There are a number of issues with the manuscript as it stands:
1. Fig. S1: For panels B-E, please consider to indicate cancer types.
2. How and why the authors choose 39 core TGF-# genes. There are many TGF# associated
genes and TGF# signatures. Please discuss the difference with others.
3. The TGF#-associated signatures of STAD was quiet difference from others. Please discuss
about it.
4. How the authors defined TGF# specific expressing miRNAs? It is not clearly explained.
5. In Figure 4B, the heatmap shows the most significantly down-regulated 20 miRNAs in the
TGF#¬¬high group. However, the legend indicated LogFC. Please clarify it.
6. Why the authors used Pearson correlation for all analysis of correlation? Do they all meet the
requirements of Pearson correlation coefficient?
7. Please correct several grammatical errors.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 6 Date: 12 Apr 2021
Reviewer's report:
It is an interesting paper that helps to understand TGF beta signaling and its potential therapy in
GIAD. The authors carefully revised the manuscript, and answered my questions, so I suggest
to accept this paper.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 6 Date: 15 Apr 2021
Reviewer's report:
1. Regarding the previous question 3: Do you mean that many of the mutations and CNVs in
Fig. 2b lead to loss of function of TGF-b-related genes such as SMAD4? Why does it happen
limited in STAD? The authors should explain it in the main article.
2. Regarding the previous question 4: The authors need to describe how BRAF-V600 inhibitors
affect TGF-b signaling and provide references about it in the main article. It does not mean the
reference should be changed.
3. What is the advantage of using clustering instead of classification by TGF-score in ssGSEA?
Is it because it only requires limited-genes expression data? Is the DNN model useful because
that makes it possible to classify TGF-b subtypes by the only top 10 genes signature? I suggest
that the authors make these points more clear to improve the article.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 6 Date: 24 Apr 2021
Reviewer:  Genwen Chen
Reviewer's report:
The study by Zhang et al. analyzed the TGF#-associated molecular features in GIAD. They
revealed comprehensive networks of TGF#-associated mRNAs, miRNAs, and proteins. Overall,
the manuscript is well organized but with little novelty, because the TGFb pathway was well-
known and widely studied. There are a number of issues with the manuscript as it stands:
1. Fig. S1: For panels B-E, please consider to indicate cancer types.
2. How and why the authors choose 39 core TGF-# genes. There are many TGF# associated
genes and TGF# signatures. Please discuss the difference with others.
3. The TGF#-associated signatures of STAD was quiet difference from others. Please discuss
about it.
4. How the authors defined TGF# specific expressing miRNAs? It is not clearly explained.
5. In Figure 4B, the heatmap shows the most significantly down-regulated 20 miRNAs in the
TGF#¬¬high group. However, the legend indicated LogFC. Please clarify it.
6. Why the authors used Pearson correlation for all analysis of correlation? Do they all meet the
requirements of Pearson correlation coefficient?
7. Please correct several grammatical errors.
Review for 10.1186/s12876-021-01869-4 (2021)

Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 9 Date: 19 Jun 2021
Reviewer's report:
The revised manuscript has a clear idea and results for the function of TGF-# signaling in
Gastrointestinal adenocarcinoma. Especially, it explored the therapeutic potential that is new
and interesting for TGF-# research field, so I suggest to accept this paper.
One small mistake in line 367 '' which could which can ''
Review for 10.1186/s12876-021-01868-5 (2021)

Title: Influence of low FODMAP-gluten free diet on gut microbiota alterations and symptom
severity in Iranian patients with irritable bowel syndrome
Version: 4 Date: 02 Apr 2021
Reviewer's report:
The study is well structured and well designed, however, minor revision i required.
1) Minor English grammar revision is required. There are several grammatical mistakes.
2) Figures 2, 3 and 4 are considered as repeated information. Please select 2 of them.
3) Low FODMAP diet is considered as a broader dietary restriction than gluten free diet. Usually
only low FODMAP diet is sufficient in decreasing IBS symptoms, so what is the benefit of
adding additional dietary restriction to IBS patients in form of Gluten free diet especially if the
combination showed only 73% response rate (which is the same as low FODMAP diet alone)?
Please elaborate.
4) Why did you use the word microbiome instead of microbiota?
5) Some of the references are old and should be updated. Too many references for an original
article, consider to reduce them.
6) Please use ''original'' articles instead of ''review'' articles for citation when referring to
microbiome changes, for example citation nr. 14.
7)Under discussion, the authors stated that Actinobacterium was non-significantly increased
contra to other studies where dietary changes lead to a reduction in these bacteria. Don't you
think that is it overstated to say that there were contradictions between the results of different
studies since yours showed a non-significant change?
8) Under discussion: The paragraph from lines 282-284 (Therefore, it is noteworthy to
administrate the diet or a combination of diets of choice for gut microbiota-associated disorders
such as IBS in order to normalize the dysbiotic communities of microbiota) should be moved
down to paragraph lines 304-308 (Our data...etc.).
Review for 10.1186/s12876-021-01863-w (2021)

Title: Contamination of Single Fluid-Filled Intragastric Balloons with Orogastric Fluid is not
Associated with Hyperinflation: An Ex-vivo Study and Systematic Review of Literature
Version: 1 Date: 21 Apr 2021
Reviewer's report:
I was delighted to review the current study. From my point of view this manuscript is not eligible
for publication.
Review for 10.1186/s12876-021-01863-w (2021)

Title: Contamination of Single Fluid-Filled Intragastric Balloons with Orogastric Fluid is not
Associated with Hyperinflation: An Ex-vivo Study and Systematic Review of Literature
Version: 1 Date: 30 Apr 2021
Reviewer:  Dimitrios Schizas
Reviewer's report:
Congratulations, this is a very interesting study.
However, there are a few issues i want to point out:
1. In my view the sample size is very small to elucidate possible causative factors for IGB
hyperinflation which is a relatively rare complication of IGB application.
Did you run a statistical power analysis in order to decide about the groups' size ?
Otherwise, you should include this in your limitations.
2. Is the IGB hyperinflation definition common in all cases included in your systematic review.
If not, please add a collumn with the IGB hyperinflation definition for each study.
Review for 10.1186/s12876-021-01863-w (2021)

Title: Contamination of Single Fluid-Filled Intragastric Balloons with Orogastric Fluid is not
Associated with Hyperinflation: An Ex-vivo Study and Systematic Review of Literature
Version: 1 Date: 09 May 2021
Reviewer:  Katerina Kotzampassi
Reviewer's report:
The present scientific work is a sophisticated combination of a review of the literature [just 10
publications – 11 cases] plus an ex-vivo experiment. The authors try to investigate the reported
phenomenon of spontaneous hyperinflation of fluid-filled intragastric balloons # which may be
the cause of abdominal discomfort in a few cases in the literature # which led the FDA to issue
an update for potential risk.
It is a well-designed and well-written study.
I have only two comments to the experimental part:
1. The size of the balloon “they measured in two dimensions using a flexible tape” is called
“perimeter” and not “diameter”. This is also prominent by the number they present, 33,5cm
2. The authors used orogastric contents to “contaminate” the balloon filling, simulating the entry
of gastric contents into the balloon either through its valve or by means of wall permeability.
Whatever the mechanism, if any, the majority of patients remain under proton pump inhibitors
treatment throughout the 6mo having the balloon in the stomach; that means their gastric content
is of less acidity [higher pH] in relation to that used in their experiment. I would like to read
a comment on it.
Katerina Kotzampassi, MD, PhD
Surgeon-Endoscopist
Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
Review for 10.1186/s12876-021-01863-w (2021)

Title: Contamination of Single Fluid-Filled Intragastric Balloons with Orogastric Fluid is not
Associated with Hyperinflation: An Ex-vivo Study and Systematic Review of Literature
Version: 3 Date: 31 May 2021
Reviewer:  Katerina Kotzampassi
Reviewer's report:
Thank you for answering all my questions/comments
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 2 Date: 02 Jan 2021
Reviewer's report:
This study explored the role of AKI in the prognosis of cirrhosis with acute variceal bleeding.
This subject is very important for clinical practice. But current study might have some flaws.
My comments regarding this work are as follows.
1. Was this study approved by the local ethics committee? If yes, please provide ethics number.
2. The sentence “The remaining 546 episodes in 390 patients with AVB were finally selected
for analysis (Figure 1).” should be included in the section of results.
3. As we all known, diabetes might be associated with the prognosis of cirrhosis with GIB
(PMID: 25874528 and PMID: 31512140). Can the author provide relevant data?
4. The diagnosis of ICA-AKI is defined as an increase of # 0.3 mg/dL during 48 hours or # 50%
over baseline in serum creatinine levels. The time frame is important for the diagnosis of ICA-
AKI. Please properly cite the diagnostic criteria.
5. How many patients were diagnosed AKI according to the conventional AKI criteria?
6. “Stage 1A and Stage 1a”. Please be consistent.
7. In this study, the different between ICA-AKI and conventional AKI in predict the mortality
of AVB should be detailed description.
8. Many grammatical errors which need revision by English native speaker.
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 2 Date: 06 Jan 2021
Reviewer's report:
In this study, the authors used ICA diagnostic criteria for AKI to perform risk factors analysis
for AKI and AVB and to analyze risk factors for death within 6 weeks of AVB.
Here are some questions and suggestions for the author to answer and compose.
1. We know that the incidence of AKI in patients with cirrhosis is very high, and because
the etiology is complicated, maladaptive or unrecovered AKI can be transitioned to CKD. The
authors didn't mention how to screen these patients who had AKI shortly before the enrollment.
2. There are many similarities between the pathophysiological mechanism of hepatorenal
syndrome and prerenal AKI. How to clearly distinguish the etiology of the two?
3. The ICA diagnostic criteria for AKI adopted in this paper did not include the urine volume
standard. Is it the lack of urine volume data or other reasons?
4. The author wrote "The 3 patients who died did not meet The conventional AKI criteria but
met The new ICA-AKI criteria". Can The diagnostic criteria of ICA and KDIGO be compared?
i.e. through the ROC curve?
5. What multivariate analysis method did the author use to determine the risk factors for AKI?
Logistic regression? Please mention it in the Methods paragraph.
6. Since the authors concluded that risk factors for AKI include HCC and MELD scores, further
subgroup analysis or propensity score matching should be performed in the analysis of whether
AKI causes short-term death in order to eliminate inherent bias.
7. The author wrote "These findings suggest that the cut-off value of serum creatinine at 1.5 mg/
dL has a significant effect on the 6-week mortality. "How is the cut-off value derived? Arbitrary?
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 2 Date: 12 Jan 2021
Reviewer's report:
The authors explore the role of AKI on survival after variceal bleeding in cirrhotic patients
- The study, although retrospective, includes a consistent number of cases but therew are some
points of concern that could have influenced the results.
1. The authors stated that 128/153 patients had diagnosis of AKi at admission while 7 developed
it during the ho.spitalisation. ICA AKI criteria establish an increase of 0.3 mg creatinine within
48 h or an increase>50% creatinine from baseline within 3 months.
The authors included cases with a baseline levels of creatinine>3 months  till 1 year. In patients
with advanced liver cirrhosis( as the majority of patients included) it may be infuenced by many
factors and can be fluctuating so creatinine value older than three months should be sxluded
from the analysis.
2. How many patients had diagnosis of AKi with a creatinine increase of 0,3 mg within 48 hours?
3.How many patients had diagnosis of AKI with an increase of creatinine >50% from baseline
within 3 months?
4.It is necessary to describe in the text how the authors diagnosed the causes of AKi
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 3 Date: 12 Apr 2021
Reviewer's report:
My comments regarding this work are as follows.
1. How does the current study suggested that ICA-AKI can detect renal dysfunction in AVB
patients earlier?
According to the conventional diagnostic criteria of AKI, 97 (17.8%) patients developed AKI
within 42 days. According to the ICA diagnostic criteria of AKI, AKI was present in 128 (83.7%)
patients at admission, whereas 7 (4.6%) had AKI beyond 5 days of hospitalization. The number
of AKI differed by 38 cases for both diagnostic criteria. What are the characteristics of these
patients? For example, which stage of ICA-AKI are these patients belong?
The authors simply compared the number of people diagnosed and the mortality rate between
the two diagnostic criteria. Is the number of newly diagnosed persons in ICA standard, which
missed by conventional standard, due to their mild of AKI?
2. The method of calculation of mortality in patients with AKI seems to be different for the two
diagnostic criteria. In conventional criteria, mortality is calculated from the number of patients
(41.2% (40/97)). In the ICA criteria, Mortality was calculated from the number of AKI events
(28.1% (43/153)).
3. Can the author provide relevant data regarding the diabetes? In the reply of authors, “Although
our paper is retrospective study, diabetes did not affect mortality in patients with variceal
bleeding.”
I don't think this problem can be solved by a simple description. Data should be provided to
explain this.
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 3 Date: 14 Apr 2021
Reviewer's report:
It should be useful to include the composition of baseline creatinine used in the study  in the
text or at least as supplementary material since the choice of baseline creatinine more than three
months before is out the ICA-AKI criteria
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 3 Date: 14 Apr 2021
Reviewer's report:
1.Although the diagnostic criteria and staging of ICA-AKI are very similar to the traditional
AKIN and KDIGO staging, I would favor the use of specific diagnoses and staging for specific
types of AKI, such as HRS.
In this paper, the definition of conventional AKI is simple. Can the authors use AKIN or KDIGO
definition to define conventional AKI and clarify the advantages of ICA?
For example, compare which diagnostic criteria has a higher incidence of AKI and which stage
is an influential factor in mortality.
If the results showed that both are similar, then why did the authors recommend the ICA
diagnostic criteria for patients with variceal bleeding.
2.“These findings suggested that the cut-off level of serum creatinine at 1.5 mg/dL has a
significant effect on the 6-week study.” This statement makes no sense because the authors have
previously shown that the mortality rate for all stages of ICA-AKI is higher than that for non-
AKI.
3."Patients with AKI stage 1b had higher 6-week mortality rate (46.7%; P = 0.080) than those
with initial AKI stage 2 (25.6%); However, this difference was not significant. " Confusing,
since it is not statistically significant, why is stage 1b higher than stage 2?
4.Although the article has been revised by an English editor, there are still some mistakes in
grammar or tense. “Effect of AKI on survival These findings suggest that the cut-off level of
serum creatinine...” It should be in the past tense.
Review for 10.1186/s12876-021-01862-x (2021)

Title: Impact of Acute Kidney Injury on Mortality in Patients with Acute Variceal Bleeding
Version: 4 Date: 08 May 2021
Reviewer's report:
The authors consistently stated that the ICA criteria can identify AKI "earlier" than conventional
criteria, but provided only 56 cases in which AKI was not diagnosed by conventional criteria,
and highlighted 3 of these deaths in an attempt to show that conventional criteria underestimate
the complication.
But like other reviewers, I wish the authors had more convincing evidence to back up their
"earlier" claim.
Review for 10.1186/s12876-021-01785-7 (2021)

Title: Combination of tumor markers predicts progression and pathological response in patients
with locally advanced gastric cancer after neoadjuvant chemotherapy treatment
Version: 3 Date: 02 Jan 2021
Reviewer's report:
This paper described that tumor marker between neoadjuvant chemotherapy and operation could
predict progression free survival and pathological response in patients with locally advanced
gastric cancer. This study is very attractive to clinician and well written. But it does not reach
the accept level to this journal.
[Major points]
1. The meaning to investigate the prediction survival in preoperatively after chemotherapy is
unclear in Introduction. It is not enough that there are few reports about that. For example,
FLOT or MAGIC protocol have problem as these regimens include postoperative chemotherapy
regardless pathological findings. Patients undergo planned chemotherapy after surgery, even if
there was no response pathologically.
2. Model 2 of Table 4 and change of TM (Table 6 and Fig. 6) seem to be not necessary in this
paper. There are redundant and let readers difficult to focus on main point of this article.
3. First paragraph of discussion is not appropriate. If authors want to mention its contents, these
should be located in Introduction. It is better to describe summarized main findings of the study
in first paragraph of Discussion.
[Minor points]
1. Abbreviation is not appropriate in running head.
2. This study is retrospective analysis and patient accumulation have taken long time. It seems
that there was time bias. Actually, there was many regimens of neoadjuvant chemotherapy. It is
better to mention about this issue in limitation paragraph. If possible, time should be included
in multivariate analysis; ex: 2006-2011 vs. 2012-2017.
3. There was no criteria of adaptation of NACT in Methods.
4. Eligible patient number was doubled in Methods and Results.
5. Interpretation and explanation should not be in Results. Last sentence of 2nd paragraph in
Results should not be there.
6. Author mentioned about overall survival in 3rd paragraph. There is a paper about DFS
surrogation for OS (J Natl Cancer Inst. 2013 Nov 6;105(21):1600-7).
Review for 10.1186/s12876-021-01785-7 (2021)

Title: Combination of tumor markers predicts progression and pathological response in patients
with locally advanced gastric cancer after neoadjuvant chemotherapy treatment
Version: 3 Date: 06 Jan 2021
Reviewer's report:
The present study examined the clinical value of a new scoring system named post-neoadjuvant
chemotherapy treatment (NACT) combination of serum tumor markers (post-NAC CTM)
involving CEA, CA19-9, and CA 72-4 for predicting pCR and prognosis in patients with locally
advanced gastric cancer. Although this paper included some important data, there were several
concerns as below.
Major comments
1. How can we make use of the findings of this study in actual clinical practice? In the
prediction of pathological response of NACT, pre-treatment parameters including CTM seem
to be clinically more useful compared to post-treatment parameters. Therefore, the authors need
to show the clinical value of post-NAC CTM in comparison with that of pre-NAC CTM. Was it
necessary to include cases with normal pre-NAC CTM value in this study? It may be interesting
to do same analyses by targeting only cases with high pre-NACT CTM value. On the other hand,
in the prediction of postoperative prognosis, ypStage seems to be more reliable compared to post-
NAC CTM. Can post-NAC CTM affect the indication of surgery or post-operative treatment
strategy such as adjuvant chemotherapy? Please give enough discussion of this point.
2. Please give the comments about the reasons why post-NACT CTM predicted pCR and
prognosis. Did post-NACT CTM reflect residual tumor burden?
Minor comments
1. Please add the indication for NAC and postoperative adjuvant chemotherapy to the method
section.
2. How many patients with pCR were there after NACT?
3. There were two Table 4, and no Table 5.
4. There were many mistakes in the grammar that need to be corrected.
Review for 10.1186/s12876-021-01785-7 (2021)

Title: Combination of tumor markers predicts progression and pathological response in patients
with locally advanced gastric cancer after neoadjuvant chemotherapy treatment
Version: 5 Date: 10 Mar 2021
Reviewer's report:
This paper described that tumor marker between neoadjuvant chemotherapy and operation could
predict progression free survival and pathological response in patients with locally advanced
gastric cancer. This study is very attractive to clinician and well written. But it does not reach
the accept level to this journal.
[Major points]
1. The meaning to investigate the prediction survival in preoperatively after chemotherapy is
still unclear. It is better that authors mention about residual tumor burden more.
2. Discussion is not sufficient. Biological mechanism for correlation between tumor marker and
long-term outcomes should be described.
Review for 10.1186/s12876-021-01866-7 (2021)

Title: Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical
significance and natural course
Version: 1 Date: 28 Apr 2021
Reviewer's report:
This is an observational study that retrospectively examined the clinical features of non-specific
small ulcers at terminal ileum that are often observed in patients with ulcerative colitis. In this
study, the etiology of this terminal ileal ulcers and its significance in ulcerative colitis remain
unclear, but its clinical features have been clarified by detailed examination. That is, although
this ulcer is more frequently observed in ulcerative colitis than in asymptomatic patients, it is
less related to the clinical course and long-term prognosis of ulcerative colitis, and it shows a
high rate of self-limiting cure.  This fact is also considered to be meaningful in the medical care
of ulcerative colitis. Based on the above, we believe that this paper is suitable for publication,
but we believe that the following points need to be corrected and added.
Minor point:
(1) It is necessary to show a typical histopathological image of the terminal ileal ulcer.
(2) It is desirable to show if the dose rate of NSAIDs and antibiotics is known when colonoscopy
confirms terminal ileal ulcer.
(3) Were additional tests performed for the purpose of investigating the cause of ulcers for which
self-limiting cure was not confirmed by follow-up?  If there are cases in which the etiology of
the ulcer has been identified, these should be presented.
(4) If there are cases in which upper endoscopy or capsule endoscopy is performed during the
follow-up period after the detection of terminal ileal ulcer, it is desirable to add the results as
well.
Review for 10.1186/s12876-021-01866-7 (2021)

Title: Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical
significance and natural course
Version: 1 Date: 28 Apr 2021
Reviewer:  Hans Strid
Reviewer's report:
General Comments to the Authors
The main objective of this retrospective study was to assess the frequency of ulcers in terminal
ileum in patients with ulcerative colitis (UC). The authors also wanted to evaluate the clinical
consequences of these ulcers. 397 patients with UC and successful intubation of terminal
ileum were found and 41 (10.3%) showed TI ulcers. There was no difference in the clinical
characteristic (baseline data, disease activity, endoscopic score, and so on) between patients with
and without TI ulcers. In 30 of the 41 patients, a follow-up colonoscopy was performed and in
a majority (77%) the ulcers were resolved.
The data of the study are rather novel. However, the retrospective design of the study is a
drawback and makes the results unreliable.
Specific Comments to the Authors
Abstract
No comments
Introduction
No comments.
Methods
There are no evaluation of NSAID use which is a weakness of the study. This has already been
stated by the authors.
In most of patients with ulcers in the terminal ileum, assessment of the small intestine should be
performed. It would strengthen the manuscript if information of MRI and/or capsule endoscopy
assessment is available.
There are no control group of patients without UC (IBD) undergoing colonoscopy in the study.
Results
The result part is generally somewhat thin (few results)
Discussion
In the Discussion, the authors stated that TI ulcers were more common in patients with UC
compared with patients without UC. However, as mentioned before a control group is lacking.
Review for 10.1186/s12876-021-01866-7 (2021)

Title: Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical
significance and natural course
Version: 2 Date: 03 Jun 2021
Reviewer's report:
This retrospective observational study of nonspecific small ulcers of the terminal ileum in
patients with ulcerative colitis is certainly limited by the fact that it is not a comparative study
with a healthy control group. However, small non-specific ulcers in the terminal ileum are not
uncommon in the daily practice of patients with ulcerative colitis, as demonstrated by the authors'
results. For this reason, additional examinations can be carried out by certain doctors. In this
study, in comparison with previous reports, non-specific small ulcers of the terminal ileum were
more often observed in patients with ulcerative colitis than in healthy subjects, and about 80%
of them healed spontaneously. This new finding non-specific small ulcers in the terminal ileum
in patients with ulcerative colitis have an enough significance in everyday practice, although the
pathological significance of such lesions is limited. In conclusion, I consider that this revised
paper, is worthy of publication.
Review for 10.1186/s12876-021-01795-5 (2021)

Title: The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in
alcohol-related liver disease: A cohort study.
Version: 1 Date: 08 Feb 2021
Reviewer's report:
This is an interesting observational cohort study related to The Enhanced Liver Fibrosis (ELF)
test as a serological biomarker for fibrosis staging and as a prognostic factor in alcohol related
liver diseases.
The paper is interesting but needs some changes from my point of view.
786 tertiary care patients with alcohol-related liver disease due to alcohol (n=81) and non-
alcohol aetiologies (n = 705) – this sentence is a little confusing, please rephrase.
The Enhanced Liver Fibrosis (ELF) test is a non-invasive test that combines measurements of
three markers of hepatic extracellular matrix to generate a unitless numerical score.(11) – the
markers should be specified, especially since you have them at abbreviation. Please insert them
also in the text. References should be placed before the point from the sentence end everywhere
in the text.
ELF performs well as a diagnostic test for fibrosis – it is not a diagnostic test, but it is a non-
invasive test that estimates liver fibrosis. Please rephrase.
Although concern exists that ongoing alcohol consumption may affect the levels of individual
ELF constituents, a recent study validated the use of ELF in detecting significant and advanced
fibrosis and cirrhosis in ARLD.(13, 18) – reference 13 is related to this, reference 18 should be
placed before comma since is related to the first part of the sentence.
Setting: Secondary care – in the abstract it is presented that the study was performed in tertiary
care centres?
Conclusion: We found that ELF performed well as both a diagnostic and prognostic marker of
fibrosis severity in ARLD – the test can not be used for diagnosis of any stage of fibrosis so you
should specify in conclusion that performed well for staging moderate and advanced fibrosis.
Review for 10.1186/s12876-021-01795-5 (2021)

Title: The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in
alcohol-related liver disease: A cohort study.
Version: 1 Date: 26 Feb 2021
Reviewer's report:
Comment to the author:
Connoley, et al. have examined the diagnostic and prognostic performance of the Enhanced
Liver Fibrosis. The study provide us with important results in daily practice. However, there are
some concerns as listed below;
Study design is questionable. The time period between cohorts 2 and 3 is more than 10 years
apart. Because of the advances in treatment of cirrhosis, it raises concerns about examining the
prognosis of these two cohorts simultaneously. Cohort 1 was excluded, and the population of
cohort 2 is small. An analysis of cohort 2 alone would be show more truth. Is it possible to
analyze only cohort 2?
Review for 10.1186/s12876-021-01795-5 (2021)

Title: The Enhanced Liver Fibrosis test maintains its diagnostic and prognostic performance in
alcohol-related liver disease: A cohort study.
Version: 2 Date: 10 Apr 2021
Reviewer's report:
The author has answered my questions appropriately. I am concerned about the differences in
historical background between the # cohorts, but I decided to accept the manuscript.