JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02197-x (2022)

Title: Additive effect of evaluating microsurface and microvascular patterns using magnifying
endoscopy with narrow-band imaging in gastric cancer: a post hoc analysis of a single- center
observational study
Version: 2 Date: 17 Feb 2022
Reviewer's report:
Thank you for your reply. I still have some concerns.
Major
1. Cohen's kappa is used to compare two raters, but Fleiss' kappa is suitable for more of them.
Therefore, to keep high level of statistical analysis of the manuscript it should be calculated
accordingly.
Another example: Roma#czyk M et al. Scoring system assessing mucosal visibility of upper
gastrointestinal tract: The POLPREP scale. J Gastroenterol Hepatol.
Minor:
1. As I have mentioned previously no definition of Accuracy is needed (lines 147-149). Accuracy
is always true positives+true negatives/all of cases.
2. Mehtods section “When multiple classifications exhibited the maximum number of answers,
the final diagnosis was regarded as “inconclusive.”” What was the threshold value?
3. As another analysis of MS alone was done, methods section should be updated accordingly.
For example, in the sentence “In this study, we aimed to evaluate the respective contributions
of MS and MV patterns for diagnosing patients with gastric cancer and to assess the differences
in diagnostic performance between the combination of MS and MV and MV alone.” MS alone
should be added.
Review for 10.1186/s12876-022-02197-x (2022)

Title: Additive effect of evaluating microsurface and microvascular patterns using magnifying
endoscopy with narrow-band imaging in gastric cancer: a post hoc analysis of a single- center
observational study
Version: 3 Date: 04 Mar 2022
Reviewer's report:
The authors have revised manuscript adequately. Congratulations on excellent work.
Review for 10.1186/s12876-022-02206-z (2022)

Title: Measuring distance from the incisors to the esophageal cancer by FDG PET/CT:
Endoscopy as the reference
Version: 1 Date: 22 Nov 2021
Reviewer's report:
The authors, using endoscopy as the reference, evaluated the accuracy of FDG PET/CT in
measuring distance from the incisors to the PET detectable esophageal cancer.
This well-written article may have some point of comment.
1. The difference of patients' posture between two examinations exists. This is a fundamental
problem.
2. The authors need to support their measurement method and proof with some pictures for
example and full pictures as supplements.
3. In deviated esophagus or tortuous esophagus, the accuracy of measurement would be
compromised.
4. The mean "absolute" difference between two measurements around 1cm would be important
clinically. If the difference is positive or negative in all cases, the clinical importance would be
less important.
Review for 10.1186/s12876-022-02206-z (2022)

Title: Measuring distance from the incisors to the esophageal cancer by FDG PET/CT:
Endoscopy as the reference
Version: 1 Date: 23 Nov 2021
Reviewer's report:
I think the study is interesting and meaningful. The results suggest that, in view of the importance
of making radiotherapy planning, the esophageal cancer patients with PET/CT undetectable
tumor can benefit from the determination of the distance from the incisors to the esophageal
tumor by endoscopic measurement.  It is a small but valuable research.
Review for 10.1186/s12876-022-02206-z (2022)

Title: Measuring distance from the incisors to the esophageal cancer by FDG PET/CT:
Endoscopy as the reference
Version: 3 Date: 07 Jan 2022
Reviewer's report:
I appreciate the author's response.
But, there are still some comments to be addressed.
1. In order to insist author's hypothesis, you are recommended to present the data about the
deviated esophagus proportion out of your patient group.
2. If the deviated or tortuous esophagus consist of a high proportion in your study group, you'd
better analyze your patients' data separately. If not, you are recommended to comment on the
need to be careful in case of tortuous or deviated esophgus.
Review for 10.1186/s12876-022-02186-0 (2022)

Title: Assessment of the diagnostic value of serum ceruloplasmin for Wilson’s disease in
children
Version: 4 Date: 17 Nov 2021
Reviewer's report:
I have put detailed my comments to your manuscript, you should receive it from the editor
It is really great work but in the present form can be very misleading for somebody who has
no experience in WD.
This paper suggests that low level of ceruloplasmin, below 16mg% is very sensitive and specific.
However, nobody even having such results should put diagnosis of WD. Having long experience
with WD, have seen many mistakes, when diagnosis was too fast.
Complexity diagnosis should be discussed.  Even DNA analysis which has 4 points, in my
opinion should have support by other metabolic tests – also there are mistakes.  It should be
discussed that ceruloplasmin results only apply only to the method used in your lab.
I do not understand who is in the group asymptomatic WD?
Results should be presented in more clear way,  details in Supplementary materials if needed.
However, changes of ceruloplasmin according to age, sex, in other liver disease, according to
genotype are interesting.
Review for 10.1186/s12876-022-02186-0 (2022)

Title: Assessment of the diagnostic value of serum ceruloplasmin for Wilson’s disease in
children
Version: 4 Date: 15 Dec 2021
Reviewer:  Manal F Elshamaa
Reviewer's report:
Dear Authors
The manuscript entitled"Assessment of the diagnostic value of serum ceruloplasmin for
Wilson’s disease in children: is welcome
Add :The: to the title        the diagnostic
Some English editing is needed
The abstract should be summarized and be concise to the most significant results. Some results
mentioned here were not mentioned in the result section text.
Introduction
The Atp7b protein is a copper-transporting ATPase expressed predominantly in the liver and
to a lesser extent in most other tissues. Mutations in the ATP7B gene lead to Wilson disease, a
copper toxicity disorder characterized by a dramatic build-up of intracellular
hepatic copper with subsequent hepatic and neurological abnormalities.
A paragraph is needed to clarify this gene and the site of the mutation studied in this research.
Abbreviations all over the manuscript should be mentioned in an expanded form first then
abbreviated afterward.
Socha reference  should be numbered in the text correctly
Materials and methods
mention the criteria of the score used for the diagnosis of WD
Results
All results need to be well organized and well arranged for more easy understanding.
P-value should be written in the results section after each result respectively. few errors in results
are mentioned here than in tables please revise well.
Table 2 Add healthy controls results and compare between two groups and add P-Value in a
separate column
Table 4 Add WS patients and healthy controls results and compare among different groups and
Add P Values in a separate column
Table 1& Table 3 Add p-value in a separate column
Figure 2 needs to be more labeled and specified to each studied group.
Discussion
Paragraphs 1 &2 need to be transferred to the results section
No need to repeat results again in the discussion section
Review for 10.1186/s12876-022-02186-0 (2022)

Title: Assessment of the diagnostic value of serum ceruloplasmin for Wilson’s disease in
children
Version: 4 Date: 19 Dec 2021
Reviewer:  Raffaele Iorio
Reviewer's report:
This study has the peculiarity of analyzing the behavior of serum levels of ceruloplasmin in
a large number of patients with WD and in a large group of healthy controls. Heterozygous
patients, patients with liver disease other than WD such as patients with acute liver failure
by infection or acetaminophen (n = 20), viral hepatitis (n = 38) and nephrotic syndrome
(n = 96) were also evaluated. The study also provides information on the potential role of
some mutations on ceruloplasmin serum levels. Considering that the potential impact of some
genotypes on serum levels of ceruloplasmin had already been reported (Nicastro E, et al. J
Hepatol 2009;50(3):555-61), I would suggest including this study as a reference. The study also
shows that in the WD patients studied the number of those with normal ceruloplasmin was very
low (6 patients with levels higher than 20 mg/dl). The authors conveniently invoke a role for
genetics. It would be interesting to have details about the genotype of these 6 WD patients with
ceruloplasmin serum levels higher than 20 mg/dl and 13 WD patients with ceruloplasmin serum
levels higher than 15 mg/dl.
Review for 10.1186/s12876-022-02186-0 (2022)

Title: Assessment of the diagnostic value of serum ceruloplasmin for Wilson’s disease in
children
Version: 5 Date: 08 Feb 2022
Reviewer:  Raffaele Iorio
Reviewer's report:
The revised version of the paper is much improved and provides useful information for clinicians
interested in WD
Review for 10.1186/s12876-022-02205-0 (2022)

Title: Correlation and Prognostic Implications of Intratumor and Tumor Draining Lymph Node
Foxp3+ T Regulatory Cells in Colorectal Cancer
Version: 1 Date: 01 Jan 2022
Reviewer's report:
1, How the authors defined TDLNs in this study? It is better to clearly show the definition of
TDLNs.
2, In Table 1, high abundance of Tregs in tumor and TDLNs were observed in T3-4, however
the authors claimed ‘both of which were more common in early T stages’.
3, In Table3, node involvement was skipped in multivariate analysis, but it seems important to
include the factor of node involvement, particularly in the study for TDLNs.
Review for 10.1186/s12876-022-02205-0 (2022)

Title: Correlation and Prognostic Implications of Intratumor and Tumor Draining Lymph Node
Foxp3+ T Regulatory Cells in Colorectal Cancer
Version: 3 Date: 03 Mar 2022
Reviewer's report:
I think that this revision has resolved many questions and made the data objectively acceptable.
Review for 10.1186/s12876-022-02199-9 (2022)

Title: Combined systemic immune-inflammatory index (SII) and prognostic nutritional index
(PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients
receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: A prospective
study
Version: 3 Date: 12 Dec 2021
Reviewer:  Yoshihiro Kakeji
Reviewer's report:
The authors  aimed to evaluate the predictive value of pre-treatment SII-PNI score on the
sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with
locally advanced gastric cancer. The pre-treatment SII-PNI score is a significant indicator
for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy
combined with XELOX chemotherapy. Although this study showed some results, which was
like putting a fifth wheel on a coach. SII, PNI, and SII-PNI score, too many parameters.
1. What difference is there among SII, PNI, and SII-PNI score?
Review for 10.1186/s12876-022-02199-9 (2022)

Title: Combined systemic immune-inflammatory index (SII) and prognostic nutritional index
(PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients
receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: A prospective
study
Version: 3 Date: 23 Dec 2021
Reviewer's report:
Peripheral blood biomarkers associated with clinical outcome in locally advanced gastric cancer
patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: A
prospective study. Ding et al. BMC Gastro
The authors present interesting data on an important question in a prospective study. However,
there are some relevant limitations. Almost a third of patients were shown to be non-responders,
what occurs to me as quite high in comparison to other studies.
Abstract:
Please, specifiy peripheral blood biomarkers as this brings already relevant information into the
abstract.
Introduction:
Treatment for locally advanced gastric cancer also may include radiotherapy and surgery.
Patients and Methods:
Recist criteria are not very well established in response assessment in neoadjuvant treatment in
gastric cancer. According to the text, all patients were resected irrespecitve of grade of response.
Grade of histologic regression has shown to be associated with OS. Thus, I recommend to
evaluate SII-PNI score according to grade of histologic regression.
Results:
Definition of PD-L1 overexpression is missing.
Discussion:
Cited article #4 did not investigate checkpoint inhibiton. Please, correct this and cite for example
first published data on checkpoint inhibiton in neoadjuvant setting (The KEYNOTE-811 trial of
dual PD-1 and HER2 blockade in HER2-positive gastric cancer.
Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L,
Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia
P, Chung HC. Nature. 2021 Dec;600(7890):727-730.)
Language: Please, correct language eg with help of a native speaker.
As I am not a statistician, please check the data by a statistician.
Review for 10.1186/s12876-022-02199-9 (2022)

Title: Combined systemic immune-inflammatory index (SII) and prognostic nutritional index
(PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients
receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: A prospective
study
Version: 3 Date: 27 Dec 2021
Reviewer:  Hiroyuki Uetake
Reviewer's report:
Major points
1) Median follow up duration should be indicated. It seems premature to determine PFS as
patients are enrolled until June 2021.
2) The author should indicate the reason for grouping into PD and non-PD. From Fig. 4, response
rate is high, and it seems better to separate responder and non-responder.
3) The total dose and relative dose intensity of oxaliplatin in each group should be indicated.
These should be related to both effectiveness and PNI.
Review for 10.1186/s12876-022-02153-9 (2022)

Title: Title: Clinicopathologic characteristics and prognosis of synchronous colorectal cancer:
A retrospective study
Version: 0 Date: 03 Dec 2021
Reviewer's report:
although this study concerns a large cohort, 26% of patients are not studied because they are
considered lost to follow-up, well above the less than 10% admitted to validate conclusions.
this loss of follow-up rate is a major limit.
this point should at least be mentioned in the discussion
the percentage of 27% of SCRC is much higher than that of the literature, and should also be
at least mentioned in the discussion.
the authors studied the operated CRCs in their structure, the conclusions can therefore only
concern the operated patients and not all the CRCs.
this study presents multiple results making reading difficult and would undoubtedly deserve to
be divided into 2 papers: 1 comparing the PCRC and the SCRC, and a 2nd comparing the EO
CRC and the LO CRC.
several factors studied, such as CA125, CA153, alphafoetoprotein, KI expression and ascites,
are of no interest and could be deleted from the article to facilitate understanding.
Review for 10.1186/s12876-022-02153-9 (2022)

Title: Title: Clinicopathologic characteristics and prognosis of synchronous colorectal cancer:
A retrospective study
Version: 0 Date: 07 Dec 2021
Reviewer's report:
Dear authors,
Despite of the limitations, your manuscript could give a highlithg about these type of CRC.
However, I consider you also need to include all tumours resected during endoscopy procedures.
Otherwise, stage 0 must be excluded.
Regards
Review for 10.1186/s12876-022-02153-9 (2022)

Title: Title: Clinicopathologic characteristics and prognosis of synchronous colorectal cancer:
A retrospective study
Version: 1 Date: 18 Jan 2022
Reviewer's report:
1. although this study concerns a large cohort, 26% of patients are not studied because they are
considered lost to follow-up, well above the less than 10% admitted to validate conclusions. this
loss of follow-up rate is a major limit. this point should at least be mentioned in the discussion.
Response: Thank you for your nice comments. There could be a misunderstanding here. As
shown in Figure 1. 26% patients (621) were excluded because they met the exclusion criteria.
Such as, Patients with any recurrent tumour, familial adenomatous polyposis, or hereditary
nonpolyposis colorectal cancer were excluded. Lost to follow-up data only accounts for a small
part of the exclusion criteria.
i don't agree with your response: 787 (33.6%)patients were excluded for exclusion criteria, of
them 26% (612) for missing data: sa there is a selection bias: only patients corectly followed
were included....this point should at least be mentioned in the discussion.
Review for 10.1186/s12876-022-02135-x (2022)

Title: The fate of indeterminate liver lesions: what proportion are precursors of hepatocellular
carcinoma?
Version: 2 Date: 28 Nov 2021
Reviewer's report:
Thank you for this very well-conducted work dealing with a very interesting topic.
I have some observations that I hope you will find constructive.
1) Your definition of "indeterminate liver lesion" is not clear at all. The reader may understand
what you are referring to in clinical practice but I think that in this setting it's important to define
the characteristics of these lesions way better.
In particular
- Some more precise and thorough references may help
- How did you come up with the keywords for your search query? This is a very delicate point
and a strong limitation of your study that largely affects the validity of your results and needs
adequate detail
- A table summarizing the characteristics of all the one hundred and nine patients should be
reported.
2) Line 145-149: This is very confusing. Is survival time referred to mortality or, as you state,  to
"interval between first MRI scan showing an indeterminate lesion and first MRI scan to diagnose
HCC (cases), or date of most recent MRI scan for patients with no HCC during follow up"? Is
mortality reported?  What's the difference between overall survival and HCC-free survival?
In addition, Kaplan-Meier curves should be reported  in the results section.
3) Line 194-199: It is not clear whether initial size is confirmed to be predictive of HCC
transformation. Interpretation of these particular results should not  be part of the results section
but rather of the discussion section. Please be sure to add some sort of clarification on these
data in the discussion.
3) Please be sure to specify all the abbreviations in the text when introduced for the first time.
Review for 10.1186/s12876-022-02190-4 (2022)

Title: Gastrointestinal symptoms are associated with a lower risk of hospitalization and
mortality and Outcomes in COVID-19
Version: 0 Date: 04 Jan 2022
Reviewer's report:
The objective of the study is to analyze the relationship between mortality and hospitalizations of
patients with COVID-19 who present gastrointestinal symptoms. Since it is not the most frequent
clinical picture in patients with SARS-COV-2 infection, I consider that including patients only
taking into account the clinical picture limits its accuracy. Patients with RT-PCR or serological
or antigenic tests that confirm the diagnosis should be included. The definition of gastrointestinal
symptoms is incorrectly expressed, including other types of symptoms, although the statistical
analysis is correct. In results, when referring to hospitalization time by groups, group 4 is missing
and group 3 is duplicated. It is necessary to review the writing by a native speaker
Review for 10.1186/s12876-022-02190-4 (2022)

Title: Gastrointestinal symptoms are associated with a lower risk of hospitalization and
mortality and Outcomes in COVID-19
Version: 1 Date: 13 Feb 2022
Reviewer's report:
It is an interesting study that shows the relationship of gastrointestinal symptoms with
hospitalization and mortality from covid-19. After the modifications the presentation is clearer
and more precise
Review for 10.1186/s12876-022-02188-y (2022)

Title: Early changes in laboratory tests predict liver function damage in patients with moderate
coronavirus disease 2019: a retrospective multicenter study
Version: 1 Date: 29 Dec 2021
Reviewer's report:
In general, a potentially good impact may come from using risk prediction model in strategic
planning, mainly in the pandemics era. I have, however, some concerns regarding the
manuscript:
1) There are several grammar and commas misplacements that my difficult reader understanding
and interpretation  of the text.
2) Some statements lack reference citation.
3) Which definition did the authors use in the stratification of mild, moderate and severe disease?
Please make it clearer in the text.  Also, please make it clearer which admission did the authors
considered, hospital, ICU, etc.
4) How were patients selected to be included in the study? Was it a convenience sample? Please
address this matter as it may contribute to bias.
5) In which period did the study take place?
6) The authors propose a model based on liver dysfunction testing and use variables such as
AST, ALT, etc. However, the statement is that it was considered as liver function damage tests
the are outside the scope of reference values. Provided that a patient, for example, have a mildly
elevated AST/ALT, for example, about 1.5x the reference value, was this considered as liver
dysfunction? Please clarify in the text how the bias and potential confounders of other causes
of test alterations was addressed.
7) Did any included patients had previous liver disease or malnutrition, for example? This may
bias sample and score. How was this potential bias reduced in the analysis? Could the authors
elaborate?
8) In the liver damage group, please explicite in the text which variables were considered altered.
Also, the submitted table is very difficult to read properly. A suggestion would be to redesigned
it in order to make it clearer for readers.
9) In the discussion, authors make a statement about vaccine production in China. Please clarify
the correlation between this and the proposed discussion.
10) Could the authors explain the following period: "Platelets are involved in the body’s
coagulation process, and abnormal PCT levels can lead to coagulation dysfunction, confirming
that coagulopathy in patients with COVID-19 is related to liver function damage". Do authors
mean PCT can cause or aid in the detection of coagulation disorders? Also, the statement also
suggest that coagulopathy in COVID-19 is related only to liver damage. This is not true. Please
address this matter.
10) If feasible, an increase in sample size would make data and conclusion more robust in order
for the score prediction to indeed have a positive impact in clinical propaedeutics.
Review for 10.1186/s12876-022-02188-y (2022)

Title: Early changes in laboratory tests predict liver function damage in patients with moderate
coronavirus disease 2019: a retrospective multicenter study
Version: 1 Date: 10 Jan 2022
Reviewer's report:
The authors built an effective model to predict the risk of abnomal liver function in covid-19
patients. Methods, results, and discussion in this manuscript was conducted well.
Drug administration is a potential factor to induce liver injury. A comparion on drug use (such
as NSAIDs) between patients with liver abnormality or not should be demonstrated in Table 2.
Review for 10.1186/s12876-022-02188-y (2022)

Title: Early changes in laboratory tests predict liver function damage in patients with moderate
coronavirus disease 2019: a retrospective multicenter study
Version: 2 Date: 29 Jan 2022
Reviewer's report:
Thank the authors for taking my suggestion into their revision. I have no other comments. This
paper can be publicated in its current form.
Review for 10.1186/s12876-022-02188-y (2022)

Title: Early changes in laboratory tests predict liver function damage in patients with moderate
coronavirus disease 2019: a retrospective multicenter study
Version: 2 Date: 01 Feb 2022
Reviewer's report:
Greetings, definitely a great improvement in reader's experience and learning. I still have,
however, some concerns regarding score use in "real world":
1) In the following statement "In this study, as long as one of the indicators of AST, ALT, GGT,
ALP, TBIL, ALB, TP was outside the reference range, it was defined as liver function damage"
the authors confirm that any value outside the normal reference range was considered as liver
function damage, with a citing study to back up the statement.  In this scenario, a high number of
patients may have been classified as with liver damage without actually having developed such
lesion in histopathology. In critical care setting,  brief changes in routine  exams may be seen
and not relate to actual clinical or permanent alterations. A high number of false positives may
arise in this setting. This may affect the score's  accuracy and wrongly classify patients as high
risk evolution and overwhelm health services critical care. Please, address this potential bias.
Also, to address this matter, I'd suggest further research and validation of the score in other
populations. If feasible, please add this in the paper.
2) I have not mistaken for procalcitonin. The consideration was made based on a similar
statement  as the one on the response "abnormal plateletcrit (PCT) can indicate blood coagulation
dysfunction, and coagulopathy in patients with COVID-19 is related to liver function damage".
To the reader, it seems as all coagulopathy in SARS-CoV-2 infection is associated with liver
damage and we know that is not the case. This should be addressed in the text.
Review for 10.1186/s12876-022-02184-2 (2022)

Title: Primary Tumor Resection with or without Metastasectomy for Left- and Right-sided Stage
IV Colorectal Cancer: An Instrumental Variable Analysis
Version: 1 Date: 20 Nov 2021
Reviewer's report:
Overall study has number of strengths, including large sample and sound statistical analysis.
Although this data is already known, such studies add value to existing data especially when
considering lack of strong randomised studies. Authors should be commended for this effort.
Line6- don’t think you can form a definite conclusion like this from this retrospective data. This
is well explained in discussion. But don’t think you can make definite conclusions in abstract.
Suggest use a different acronym for primary tumour resection plus metastatsectomy. Current
form is confusing and difficult to correlate for the reader.
Consistent with the use of MTR and metastasectomy .
Line 9-12 : previous studies have examined this to some extent ; improved
OS after metastasectomy in left than right colon cancers https://doi.org/10.1016/
j.currproblcancer.2020.100637.
What are the unmeasured variables author trying to address by IV method ? Could author make
it more clearer in the methods ?
Why Fig 1 is in pg 16 and 20- I assume this will be corrected later.  Author to review this to
avoid duplication.
Figure 3 : PTR v no PTR  or PTR v no surgery –  Could author make it clear .
Metachronous disease were not included in this study-I wonder whether database doesn’t capture
this ? this is the vast majority of stage 4 CRC therefore exclusion of this cohort is a major
limitation of this study. I suggest to mention this in the abstract and in methods.
Other limitation is the absence of mutation status and not considering this in multivariate model
as these are important prognostic factors. https://doi.org/10.1080/0284186X.2018.1487581. It
will be important to mention this in the limitations.
Is there an approval number from SEER database  or local Ethics approval for this retrospective
study ? Better to quote the reference this in the text.
Review for 10.1186/s12876-022-02184-2 (2022)

Title: Primary Tumor Resection with or without Metastasectomy for Left- and Right-sided Stage
IV Colorectal Cancer: An Instrumental Variable Analysis
Version: 1 Date: 11 Jan 2022
Reviewer's report:
In this study, Ling Yin et al. have evaluated the associations between primary tumor resection
(with or without metastasectomy) and survival in left- and right-sided stage IV colorectal cancer.
I think the research aim is relevant, and the study design seems appropriate to address that. The
epidemiological/statistical analyses seem suitable for the task, but they are quite complex, and
I think that a separate review by an epidemiologist would be useful. I think the manuscript is
quite well-written. I have just a few minor suggestions to improve the manuscript:
1. I would recommend being more cautious with implying causation (such as page 27, line 21;
"Our instrumental variable analysis shows tat PTR does not improve survival..."), considering
that this retrospective study can only show associations, not causation. Please review the whole
manuscript and reconsider such conclusions.
2.  The word"splenic" is missing from "... left-sided CRC occurs in flexure, ..." (page 5, line 21).
3. Please consider, whether all abbreviations are necessary. In my opinion, the abbreviations
make this text more difficult to read. Moreover, some abbreviations are very similar (e.g., PTL,
PTR), which further complicates the text.
4. I would recommend adding version numbers for R packages used in the study.
5. I would recommend systematically using italics for gene names (e.g., KRAS, BRAF) to
separate them from gene products.
Review for 10.1186/s12876-022-02194-0 (2022)

Title: Characterizing Reflux on High Resolution Esophageal Manometry with Impedance
Version: 1 Date: 09 Dec 2021
Reviewer's report:
The group from Temple University presents a case series of esophageal function tests in patients
and a small group of volunteers to correlate episodes of reflux during the esophageal manometry
and at the ambulatory pHmonitoring.
The idea behind the study is very interestingly; however, there are few points to be clarified
before the results can be well understood:
1)  Inclusion criteria: are these consecutive HRM for patients with clinically suspected GERD?
There is a myriad of manmetric diagnosis and some without the possibility of having GERD
(e.g., achalasia).  Why these patients were not excluded or used as "control"?
2) All patients underwent pHmonitoring? Why achalasia patients would undergo it? They may
have false reflux and confuse results
3)  The majority of patients were on PPIs. This is a SERIOUS limitation.
4)  Episodes of reflux are usually considered during LES relaxation during swallows (as a
common cavity). What the authors present at the figure 2 looks like a transient relaxation of
the LES. Is it what they were looking for? There are established criteria and protocols to search
for TRLES.
5) Statistical analysis is not appropriate. This is a diagnostic test analysis. A ROC curve could
provide a better reference value for pathologic reflux at HRM.
Minor comments:
1) Surgery is the name of a science not a procedure. Replace "surgeries" with "operations"
2) Tests can be reviewed and adapted to Chicago 4.0 version at least regarding the definition of
innefective motlity. Change in position was probably not performed to confirm EGJOO
3) "hiatal hernia" will lead the readers to interpretate it as an endoscopic finding. Please use
esophagogastric junction morphology classification instead
4) Why 12 swallows when the standard is 10?
Review for 10.1186/s12876-022-02194-0 (2022)

Title: Characterizing Reflux on High Resolution Esophageal Manometry with Impedance
Version: 1 Date: 22 Dec 2021
Reviewer's report:
The author tried to characterize reflux on high resolution esophageal manometry with Impedance
(HREMI). The idea of reflux on HREMI is novel and several issues are needed to be clarified:
1.The study population included non-obstructive upper gastrointestinal (GI) symptoms, lung
transplant evaluation, bariatric surgery evaluation or health volunteers. The population are so
heterogeneous. The diagnosis of esophageal motility disease or GERD was not clearly presented.
It is too hard to answer the issue that the prevalence of HREMI in GERD, obesity patients or
health subjects. The GERD is defined according to Lyon consensus. However, the subjects did
not receive any endoscopy and possible GERD with endoscopic erosive esophagitis may be
overlooked.
2. The questionnaire was PAGI-SYM but not common GERD self-reported questionaries such
as GERDQ, RDQ, RSI…etc. We cannot know the detailed reflux associated symptoms and
the correlation between reflux on HREMI. We also cannot know the proportion of GERD like
symptoms (ex: GERDQ>=8…etc) in patients with or without reflux on HREMI.
3.The method of HRMI was not described in detail. The discontinuation of medications and
prokinetics were not mentioned.
4. The MII-PH and ambulatory PH were not described in detailed. The discontinuation of PPI
or H2 were noted explained clearly. Some subjects were on PPI and some were off. We cannot
interpret and analyze the diagnosis of GERD together.
5. Why student’s t-test (parametric) and Mann Whitney U test (non-parametric) were both used?
What is the rationale?
6.The authors presented data in mean ± standard error of mean (SEM). SEM is hard for us to
know the outliners. I suggested to presented AET in proportion (like: AET>6%, 4-6% and <4%).
7.”The results of this study were previously presented in abstract form at the 2020 American
College of Gastroenterology Annual Meeting and discussed in more detail here”. I suggest to
delete this.
8. “If esophageal shortening was seen post-swallow, reflux on HREMI was defined as retrograde
movement of bolus detected in 2 impedance sensors above the proximal LES border of the
shortened esophagus.” Is the definition defined by another research? What is the possible
physiology meaning of this? Please discuss in discussion.
Review for 10.1186/s12876-022-02194-0 (2022)

Title: Characterizing Reflux on High Resolution Esophageal Manometry with Impedance
Version: 2 Date: 25 Feb 2022
Reviewer's report:
The authors responded well to all the points.  They clarified Reflux on High Resolution
Esophageal Manometry and GERD.
Review for 10.1186/s12876-022-02173-5 (2022)

Title: Consensus Care Recommendations for alfapump ® in Cirrhotic Patients with Refractory
or Recurrent Ascites
Version: 3 Date: 04 Dec 2021
Reviewer's report:
Aagaard et al describe a consensus statement on ALFA pump for management of refractory
ascites. There are clearly some patients with refractory ascites who will be suitable for this
procedure and so the manuscript is a useful addition to the medical literature. My comments
are below
1. Concerns remain about the high risk of adverse events, also confirmed by a recent sys
review (Lepido et al APT 2019). The authors need to address the main adverse events (and
management)  of the alfapump (maybe  in a table) so that readers are aware. There is an ongoing
trial (POSEIDIN)(again not mentioned by the authors) which I am assuming is using new
peritoneal catheter which may reduce risk of adverse events
2. The alfa pump is not routinely available at least in the UK and has undergone NICE
assessment which recommends use only in research setting .  “Current evidence on the safety
of subcutaneous automated low-flow pump implantation for refractory ascites shows there are
serious but well-recognised safety concerns, including device failure and acute kidney injury.
Evidence on efficacy is limited in quantity. Therefore, this procedure should only be used with
special arrangements for clinical governance, consent, and audit or research [IPG631]. I do not
have a sense if the same applies to other European Countries. This  issue of alfa pump availability
needs to be clearly addressed by the authors
3. The alfa pump is expensive ? 30K and this could be considered prohibitive in some healthcare
systems. Again not addressed by authors
4. Need more clarification on indication for long-term human albumin solution in those with
an alfa pump in situ
5. Is there any role of the alfa pump as a palliative intervention ?
6. The authors mention both the EASL and AASLD ascites guidelines re NSBB and refractory
ascites but make no mention of the recently published UK Ascites guidelines (Aithal GP, Gut
2021) which state until randomised high quality data is available, the current evidence base
supports the use of NSBBB when indicated in patients with refractory ascites unless alternative
markers of circulatory failure such as hypotension or reduced glomerular filtration rate are
present.
7. No references were provided
Review for 10.1186/s12876-022-02173-5 (2022)

Title: Consensus Care Recommendations for alfapump ® in Cirrhotic Patients with Refractory
or Recurrent Ascites
Version: 3 Date: 06 Dec 2021
Reviewer's report:
The authors provide consensus recommendations for patient and procedural management for
Alfa-Pump implantation for refractory ascites. The 23 recommendations are a mix between
an implantation manual and guidelines for the management of portal hypertension / refractory
ascites but they make sense, are explained in a comprehensive way and are easy to follow. A
few minor issues should be addressed:
-preimplantation phase: I am missing a comment about TIPS here. I would suggest to specifically
mention TIPS (or rather contraindications to TIPS) as one of the prerequisites to consider the
pump (it is mentioned in Table 1 but not in the text)
-recommendation 5: “Prophylaxis should ideally be continued from admission to Alfa-pump
explant.” Please check whether this would be correct and whether this is what you meant (to
me, it would make more sense to write “implantation”, but maybe I am wrong.
-Reference 7: please provide full reference
Review for 10.1186/s12876-022-02195-z (2022)

Title: Prevalence of constipation and use of laxatives, and association with risk factors among
older patients during hospitalization. A cross sectional study
Version: 0 Date: 29 Jan 2022
Reviewer's report:
This is a very interesting paper dealing with the prevalence of constipation and the use of
laxatives among older hospitalized patients
Line 21“Many older patients’ experience constipation..”: without apostrophe
Line 51 “To enhance the quality of care in relation to the bowel health of older patients’..”:
without apostrophe
Line 56  Despite being a common condition among older patient’s > patients
Line 90 Nursing diagnosis of constipation, as an actual or a potential health problem, are defined
… > probably “is”
Line 142: The authors should better explain what they mean for “altered functional status”
Line 153: The authors should highlight that they used “three different data sources… in order
to reach as complete a description as possible” as a limitation of the present study
Lines 215-218. The authors should better explain their interesting finding that  only “…18
patients (6%) had received an ICD-10 diagnosis of constipation” whereas , “from progress
notes written by RNs and physicians’ regarding signs and symptoms, 199 patients (65%) had
symptoms of constipation”.
Line 221: I am not so sure that nausea could be included among the characterizing features of
constipation
Line 227: Among stimulants did the authors include also prokinetics and secretagogues?
Lines 303-305: “This finding indicates that comorbid health conditions may have a lower impact
on the development of constipation. However, in contrast, a previous review reported that
underlying medical conditions were one of the most common risk factors for constipation”  The
authors should better explain these concepts
Line 306: Were PAMORAs prescriped in no patients treated with opioids?
In the Introduction and also in the discussion, when the authors deal with the different definition
of chronic constipation and the self-diagnosed constipation they could profitably use the
paper by Bellini et al. “Different perception of chronic constipation between patients and
gastroenterologists”  NGM 2018.
Review for 10.1186/s12876-022-02129-9 (2022)

Title: Prognostic Role of Multiparameter MRI and radiomics in Progression of
Advanced Unresectable Hepatocellular Carcinoma Following Combined Transcatheter Arterial
Chemoembolization and Lenvatinib Therapy
Version: 2 Date: 30 Nov 2021
Reviewer's report:
The study is interesting and overall well written.
I have the following suggestions to improve the quality and clarity of the paper:
1) Were the accuracy of the models compared? If so, how? I would suggest to express also the
AIC (Akaike information criteria) to express the comparative quality of the models.
2) A calibration curve would be useful to assess the goodness of fit of this model
3) The lack of a proper validation represents a major drawback and it should be assessed as such
in the Discussion
4) Other important limitation is the lack of data on overall survival.....
5) I would recommend to discuss briefly the impact of eventual systemic treatment on PFS after
TACE (in this regard cite the example of regorafenib and the recent paper: PMID: 31877664
and the example of very recent checkpoint inhibitors with the paper: PMID: 33086471)
Review for 10.1186/s12876-022-02187-z (2022)

Title: Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Adverse effects: A Double-Blind Placebo-Controlled Randomized Clinical
Trial
Version: 2 Date: 03 Nov 2021
Reviewer's report:
Reviewed of “Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Side Effects: A Double-Blind Placebo-Controlled Randomized Clinical Trial”
This was a single center, double-blind, randomized, placebo-controlled trial to evaluate
the efficacy of Quadruple Therapy with probiotic supplements containing S. boulardii or
Lactobacillus reuteri (DSMZ 17648 strain) on eradication rate of H. Pylori infection.
Besides, I have some concerned
Major
1. Why choice the age less than 15 year of age in the exclusion criteria#Most studies setting of
adults are 18 years old.
2. What definition of positive of Helicobacter pylori (H.pylori)#Urea breath test (UBT) ,
pathology, serum H.pylori antibody, Rapid urease test, stool H.pylori antigen, each tests has the
different sensitivity, specificity, diagnostic rate.
3. How to confirmed the H.pylori eradication status#Urea breath test (UBT) is most reliable
diagnostic tool in the most study.
4. Why the study did not evaluate the sample sizes#
5. Did the study performed Helicobacter pylori resistant survey#There were clarithromycin
in the Quadruple Therapy regimen. However, clarithromycin resistant rate were high in some
country, and it may affect H.pylori eradication rate.
6. The side effects of Quadruple Therapy were easily observated. Study subjects,  dropped,
withdrawal study had been mentioned in the previous studies. How many patients adhesion more
the 80% and complete full regimen#
Patient compliance, antibiotics resistant were the most important factors of Eradication of
Helicobacter Pylori.
Minor
1.What kinds of proton pump inhibitors choice in this study#
esomeprazole. (Nexium®) # lansoprazole (Takepron®. OD) # pantoprazole (Pantoloc®) #
rabeprazole(pariet).
2.I suggested some reviewed literatures about why S. boulardii is superior than L. reuteri, on
eradication of H. Pylori in the discussion.
Review for 10.1186/s12876-022-02187-z (2022)

Title: Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Adverse effects: A Double-Blind Placebo-Controlled Randomized Clinical
Trial
Version: 2 Date: 13 Nov 2021
Reviewer's report:
The resistance of Helicobacter pylori to antibiotics leads to its eradication rate decreasing year
by year. Combined application of antibiotics can improve the curative effect. The combined use
of antibiotics increased the incidence of adverse reactions. The research on adding probiotics to
Helicobacter pylori eradication treatment is increasing in recent years. The authors investigated
the effect of quadruple treatment with Saccharomyces boulardii or Lactobacillus reuteri on
the eradication of Helicobacter pylori and side effects of the treatment. They found that
the use of probiotic supplements containing S. boulardii or Lactobacillus reuteri improved
the eradication rate of Helicobacter pylori infection, but it was not statistically significant.
S. boulardii supplements could significantly reduce some side effects of Helicobacter pylori
eradication therapy.
There are some problems:
Why all the subjects continued to take proton pump inhibitor (PPI) alone for 14 days after
eradication treatment?
Did all patients complete post-treatment follow-up? No lost patients? Is there any patient who
did not complete the treatment due to adverse reactions?
One limitation of this study is the small sample size.
Review for 10.1186/s12876-022-02187-z (2022)

Title: Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Adverse effects: A Double-Blind Placebo-Controlled Randomized Clinical
Trial
Version: 5 Date: 23 Jan 2022
Reviewer's report:
This article has been revised and can now be accepted and published.
Review for 10.1186/s12876-022-02187-z (2022)

Title: Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Adverse effects: A Double-Blind Placebo-Controlled Randomized Clinical
Trial
Version: 5 Date: 24 Jan 2022
Reviewer's report:
After major revised of manuscripts, I still have some concerned
1. Positive of Helicobacter pylori (H.pylori)
Authors used pathology & for confirmation of H. pylori eradication & follow up, H. pylori stool
Ag.
(1) Suggested to add ‘pathology with Giemsa stain “in sentence.
I had concerned which part was taken biopsy (Antrum or body, or both).
H.pylori detection rate was poor in antrum of atrophy gastritis.
(2)Which stool kit of H. pylori stool Ag were used? Different kit has the different sensitivity,
specificity, diagnostic rate.
2.What kinds of proton pump inhibitors choice in this study#
esomeprazole. (Nexium®) # lansoprazole (Takepron®. OD) # pantoprazole (Pantoloc®) #
rabeprazole(pariet).
Author did not answer this question.
3. Methods, page 5, lines 102 - 109
May consider revise this part briefly because most parts are duplicated in the other parts of the
manuscript(result section).
4. Methods, page 6, line 131 and lines 122 - 124.
"Patients with the history of gastric surgery" and "patients with the history ... stomach or ..."
are duplicated.
Authors did not revise these parts.
5. Limitations, page 12, line 283
"The main limitation of this study was poor cooperation" Some patients refused to come for H.
pylori stool Ag testing. But no study dropped out?
Review for 10.1186/s12876-022-02187-z (2022)

Title: Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or
Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori
and Treatments# Adverse effects: A Double-Blind Placebo-Controlled Randomized Clinical
Trial
Version: 6 Date: 25 Feb 2022
Reviewer's report:
This article has been revised as Editor and reviewers comments and can now be accepted and
published.