JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-021-01708-6 (2021)

Title: Understanding Patient Journey in Ulcerative Colitis Prior to Biologic Initiation: A 5-Year
Exploration
Version: 3 Date: 13 Jan 2021
Reviewer's report:
This is a very interesting work. Having acces to the data, some additional analyses can be
performed.
Please find my detailed comments below.
The conclusions concern remission, progression, and mucosal healing while these outcomes
were not tested within the analysis. I advise to change the conclusions.
The conclusions and the description of the results may be more detailed. As we can see from the
Table 1, the significant increase is observed almost only in the year 1, and the values seem to
be stable from the year 5 to the year 2. Additionally, the mean duration of oral 5-ASA and other
IMM decrease over time. These are interesting findings that should be describedl in more detail.
If you have access to the data, I suggest to include additional aspects in the analysis; two first
are the most important ones:
- severity of the disease: mild, moderate, severe - how many patients with each type of severity
within 5 years and within each year
- status of the disease: remission, active - how many patients in remission within 5 years and
within each year
- surgery (yes/no) within the 5 years (and within each year),
The country of interest should be mentioned in Methods. It can be found somewhere, but not in
the place where it should be (Methods/Data source or Introduction/study aim).
It would be very interesting to assess the factors that influence the need for biologic treatment
(for further analysis).
There are some minor editing issues: the lack of commas (line 27, 37), no space after dot (line
51, 53), no space between reference (line 53).
It should be corticosteroids treatment in the line 39.
In line 65 - what does "adult outpatients" mean? Shouldn't it be "adult patients"?
Figure 1 should be referenced as Supplementary Figure 1.
In Ethical consideration the part of the last sentence starting from "as" is the same as in the
previous sentence.
Review for 10.1186/s12876-021-01708-6 (2021)

Title: Understanding Patient Journey in Ulcerative Colitis Prior to Biologic Initiation: A 5-Year
Exploration
Version: 3 Date: 20 Jan 2021
Reviewer's report:
Wang et al. investigated the pre-biologic treatments of UC patients in association with health
care utilization patterns using a real-world healthcare database. Within 5 years prior to biologics,
the authors found an increasing dose and duration of systemic corticosteroid treatment which was
accompanied by an increased frequency of health care visits. Based on the results, the authors
concluded that a better risk stratification is needed to help identify patients for more timely
biologic treatment.
Major comments;
1. When the authors think is the best to start biologic treatment for potentially high-risk
(increased morbidity and health care utilization) patients based on their data?
In the Introduction, the authors discuss the potential importance of “early” biologic treatment in
a group of high-risk UC patients by comparing with CD. In CD, this usually means top-down
therapy which starts biologic treatment instead of steroids. These description (Line from 60 to
73 of Page 4) imply that some UC patients would require top-down therapy like CD. Otherwise,
do the authors mean to avoid multiple rounds of steroids before biologic treatment?
2. Is there any difference in the patient character between those who experienced treatment
burden (e.g. longer steroid duration and/or frequent health care visit) and those who did not?
Some difference might be helpful to identify patients for more “timely” biologic treatment.
Minor comments;
1. On line 137 of Page 7, “Figure 1” will be “Table 1” because there is no Figure 1 in this
manuscript.
Review for 10.1186/s12876-021-01708-6 (2021)

Title: Understanding Patient Journey in Ulcerative Colitis Prior to Biologic Initiation: A 5-Year
Exploration
Version: 5 Date: 24 Feb 2021
Reviewer's report:
This manuscript provided a real-world evidence that UC patients suffer from increasing
morbidity and treatment burden prior to biologic therapy. Although this manuscript do not tell
us when and for which patients we should think about "early" biologic treatment, the results will
still call attention to the prolonged or repeated treatment with steroids in the clinical practice.
I hope the authors extend this research and find out better risk stratification to identify patients
who can benefit from timely biologic treatment.
Review for 10.1186/s12876-021-01709-5 (2021)

Title: Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
Version: 2 Date: 10 Jan 2021
Reviewer:  Andriy E Dorofeyev
Reviewer's report:
The manuscript is devoted to the actual problem of studying new pathogenic mechanisms of
UC. Il-12 / Il-23 were selected for the study, which are targeted markers for ustekinumab
treatment. The results obtained are of practical value and can be used when choosing a drug for
the biological therapy of UC.
Review for 10.1186/s12876-021-01709-5 (2021)

Title: Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
Version: 2 Date: 26 Jan 2021
Reviewer's report:
The present study was performed to evaluate the mucosal IL-12/23 expression and its
relationship with endoscopic severity, histological activity, and UC relapse.
The manuscript proposes points of novelty about a critical role of IL-12 in UC pathogenesis and
the molecular mechanism of UC relapse. The statistical methods are adequate.
I have a couple of request:
1) Do the authors have evidence about the serum levels of IL-12 and IL-23?
2) It could be of interest to evaluate the expression of tight junctions (claudin-2 occludin and
zonulin-1) and their correlation with IL-12 expression
Review for 10.1186/s12876-021-01699-4 (2021)

Title: ROLE OF PERCUTANEOUS LIVER BIOPSY IN INFANTILE CHOLESTASIS:
COHORT FROM ARABS
Version: 1 Date: 09 Nov 2020
Reviewer:  Hironori Kusano
Reviewer's report:
The authors assessed the impact of liver biopsy (LB) in the evaluation of infantile cholestasis
and concluded that LB has high diagnostic yield in case of high suspicion of biliary atresia (BA)
and low yield in low suspicion of BA. Their patient cohort is unique and the number of cases is
high enough for sufficient assessment. The study design is very clear.
Comments;
Draw a diagram of inclusion and exclusion criteria in the study. It must be helpful for readers.
The authors should provide the diagnosis for the patients who did not undergo LB.
The authors are confusing “bile plug” with “bile duct plug”.
Currently “ballooning” is closely attached with NASH. I recommend the use of the term
“swelling”.
The quality of histological images is not good enough for publication. For example, Fig. 3A is
too small to identify the ductules.
The authors should show the bile duct proliferation and bile plugs in the figure, which were
strong indicators for BA in the study.
Add scale bar in the figure.
Review for 10.1186/s12876-021-01699-4 (2021)

Title: ROLE OF PERCUTANEOUS LIVER BIOPSY IN INFANTILE CHOLESTASIS:
COHORT FROM ARABS
Version: 2 Date: 29 Dec 2020
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
Accept, but some revisions would be needed.
Minor revisions as follows.
1. In the main text, define abbreviation again
P4, line 59 Infantile cholestasis (IC)
P4, line 65   Liver biopsy (LB)
2. In this revised manuscript, the authors provided with new information as follows; "In this
study, the diagnoses of all hereditary diseases were confirmed by molecular analysis."
- Does this mean that the authors have confirmed hereditary diseases with known genetic/
molecular information? Is it possible to confirm all hereditary diseases with molecular analyses?
Please explain these analyses what the authors have done in the Methods section?
Review for 10.1186/s12876-021-01682-z (2021)

Title: Controlling Nutritional Status (CONUT) score as a predictive marker for short-term
complications following gastrectomy of gastric cancer: a retrospective study
Version: 2 Date: 04 Jan 2021
Reviewer's report:
The authors have reported that preoperative CONUT was associated with the postoperative
complications of gastric cancer patients. There were some weak points in this study. First of all,
this paper does not follow the general formatting guidelines. It is not double-spaced, and there
is no mention of line and page numbering. Second, it has little something new. Lin JX, et al.
have already reported that CONUT score was associated with post-gastrectomy complications.
The authors should be cited for the article by Lin JX, et al.
Lin JX, et al. Which nutritional scoring system is more suitable for evaluating the short- or long-
term prognosis of patients with gastric cancer who underwent radical gastrectomy? J Gastrointest
Surg. 2020 Sep;24(9):1969-1977.
Minor comments
1) The Patients section of Methods should be described in more detail. The inclusion criteria
such as whether it is a surgical case or not, whether it is R0 or not, etc. should also be described.
2) Why are there so few laparoscopic surgeries in spite of the large number of Stage I cases?
3) The journal name in reference 28 is incorrect.
4) The year in reference 31 is wrong.
Review for 10.1186/s12876-021-01682-z (2021)

Title: Controlling Nutritional Status (CONUT) score as a predictive marker for short-term
complications following gastrectomy of gastric cancer: a retrospective study
Version: 2 Date: 10 Jan 2021
Reviewer:  Yoshihiro Kakeji
Reviewer's report:
The authors aimed to characterize the relationship between CONUT and short-term
complications following gastrectomy of GC. The manuscript contains interesting findings.
1. Is the relation between CONUT score and short-term outcomes changed through disease
stage?  How about were the relationships in early gastric cancer or in advanced ones?
Review for 10.1186/s12876-021-01682-z (2021)

Title: Controlling Nutritional Status (CONUT) score as a predictive marker for short-term
complications following gastrectomy of gastric cancer: a retrospective study
Version: 2 Date: 11 Jan 2021
Reviewer's report:
This study has a large number of cases, which is a good point. However, there are some concerns
about statistical analysis and interpretation that should be addressed.
In the multivariate analysis in Table 2, it should be explained in the statistical analysis chapter
how the variables included in the model were chosen. It seems that there are some variables that
are significant in univariate analysis but excluded in multivariate analysis.
Also, since logistic regression is not mentioned in the statistical analysis, all the analyses
conducted in the paper should be mentioned in the statistical analysis.
The authors performed ROC analysis of CONUT, ALB, PNI, and PLR, all of which have an
AUC of about 0.5, which does not seem to have predictive ability.
This may mean that there is an association with the outcome but no predictive ability.
The results of ROC analysis should not be included in the paper because it may lead to
misleading.
In Table 3, the threshold of CONUT is set to 2 for two-group comparison, but how was it
determined?How was it determined? Youden index or (0,1)-closest method? In addition, it hould
be considered what CONUT=2 means clinically.
Review for 10.1186/s12876-021-01681-0 (2021)

Title: Non-alcoholic Fatty Liver Disease and Cognitive Function in Middle-aged Adults: The
CARDIA Study
Version: 1 Date: 14 Dec 2020
Reviewer:  Yasushi Honda
Reviewer's report:
Yariv Gerber et al. investigated the association between NAFLD and cognitive function by using
Coronary Artery Risk Development in Young Adults (CARDIA) participants. This manuscript
is very interesting because it had a large number of patients and detailed data. However, there
is one serious problem. Although the authors used CT to diagnose the severity of NAFLD, CT
has insufficient accuracy for mild-to-moderate hepatic steatosis. The authors should investigate
this association using not only CT but also serum biomarkers and biomarker panels.
Review for 10.1186/s12876-021-01681-0 (2021)

Title: Non-alcoholic Fatty Liver Disease and Cognitive Function in Middle-aged Adults: The
CARDIA Study
Version: 1 Date: 22 Jan 2021
Reviewer's report:
- Introduction section: i suggest to report epidemiology data on NAFLD worldwide. In the US
and globally, NAFLD is the most common cause of chronic liver disease. By definition, NAFLD
occurs in the absence of excessive alcohol consumption,3 and is associated with CVD and
its risk factors including type 2 diabetes, obesity, hyperlipidemia, and hypertension. Such risk
factors are known to contribute to cognitive impairment with or without the mediation of CVD.
Furthermore, considering findings from previous studies suggesting that NAFLD could be an
independent CVD risk factor, it appears reasonable to hypothesize that NAFLD is independently
associated with cognitive impairment.
- Methods section: i suggest to divide the Measurements in two sub-sections "Clinical" and
"Biochemical" measurements. Also i suggest to inlcude trygliceride values in the dataset.  No
data on dietetic profiles are reeported in the text. Please improve this part.
- Discussion section: it is possible that the association between NAFLD and cognitive
impairment is an epiphenomenon, because CV risk factors and diseases are related to both
NAFLD and cognition. The key point can be represented by insulin resistance, that explain the
association between NAFLD and cognitive impairment, because insulin resistance plays critical
roles in the pathogenesis of NAFLD and Alzheimer disease.
Review for 10.1186/s12876-021-01669-w (2021)

Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 1 Date: 03 Jan 2021
Reviewer's report:
It is an interesting study about the role of ferritin on the prognosis of patients with liver disease
comments:
1. the manuscript has many grammar and syntax problems. Please try to correct them
2. In your study , patients with hepatocellular carcinoma were included. I think that this group
of patients should be excluded from the study. Presence of HCC changes the clinical and
inflammatory status of a patient. So it is wrong to  include in the same group of patients those
with and without HCC (per example compensated cirrhotic patients without HCC and those with
compensated cirrhosis and HCC).
3. You found that in compensated liver disease, low ferritin is related to increased risk for the
development of liver decompensation. On the other hand in patients with decompensated liver
cirrhosis, high ferritin levels were found to be related to an increased risk for bacterial infection.
You gave the following explanation: in the first group, the cause of low ferritin was probably
the subclinical bleeding due to the portal hypertension. In the latter group, the cause of high
ferritin was the liver insufficiency and the inflammation. However in both groups high ferritin
was related to worse outcome. It is obvious that in the group of compensated disease the results
are controversial (low ferritin increases the risk for decompensation but high ferritin worsens
the survival). It would be better for that reason to examine separately the compensated cirrhotic
patients who sustained in a compensation status during the 2 years period of follow up and on
the other hand the compensated cirrhotic patients who developed liver decompensation during
this period of time.
4. In the field of discussion you made a lot of speculations in order to explain and support your
results. Some of them are more comprehensive and some are less. It is hard for me to understand
your deduction in the 1st paragraph of page 24 : "Finally, the stronger correlation ........exactly
in this patient group". Please explain in a better way what do you mean.
Review for 10.1186/s12876-021-01669-w (2021)

Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 2 Date: 30 Jan 2021
Reviewer's report:
All comments have been addressed and been responded well. The result is statistically confirmed
from the clinical data in this paper. I suggest the acceptance of this manuscript for publication
in the BMC Gastroenterology.
Review for 10.1186/s12876-021-01669-w (2021)

Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 2 Date: 30 Jan 2021
Reviewer's report:
The investigators have given clear answers to my comments and questions
The new form of the manuscript is better than the previous one
I am very satisfied and i have nothing more to mention
Review for 10.1186/s12876-021-01667-y (2021)

Title: Symptoms and biomarkers associated with undiagnosed celiac seropositivity
Version: 1 Date: 22 Nov 2020
Reviewer's report:
a number of studies performed in the study area and except the sample size there is no novelty
in this paper. I think it can potentiality publish in the local journals
Review for 10.1186/s12876-021-01667-y (2021)

Title: Symptoms and biomarkers associated with undiagnosed celiac seropositivity
Version: 1 Date: 23 Nov 2020
Reviewer's report:
The aim of the study was to investigate whether undiagnosed CD patients have more symptoms
or affected biomarkers compared with non-CD subjects. This was accomplished by identifying
CD antibody positivity without a known diagnosis of CD in eight population-based cohort
studies comprising 16,776 participants and comparing them to matched controls.
Below are my comments:
-the CD patients are the same individuals than in the previous article by Kårhus et al Am J
Gastroenterol. Moreover the controls are a subset of controls in the same study. Therefore, I
would urge the authors to openly state this on page "materials". For the same reason, I would
suggest to present table 1 as background data (as the CD patients have already been published in
Am J Gastroenterol) refer to the table already in materials and remove it from the result section.
-I would suggest to somehow highligh (for instance bolded font or equivalent) the significant
findings.
-the authors defined CD as IgG-DGP #10.0 U/mL and/or IgA-TTG or IgG-TTG #7.0 U/mL .
However, in TTG negative individuals the positive predictive value of IgG DGP antibodies is
only 18.2% (Hoerter et al. Digestive Diseases and Sciences 2017; 62: 1272–1276). As 59 of the
identified CD cases were only IgG-DGP positive (vaailable in Am J Gastro article), not all of
them are likely true celiac disease patients. I would encourage the authors to discuss this as a
possible limitation.
Review for 10.1186/s12876-021-01667-y (2021)

Title: Symptoms and biomarkers associated with undiagnosed celiac seropositivity
Version: 1 Date: 23 Nov 2020
Reviewer's report:
Thanks for studying the topic of asymptomatic CD.
1. Please, refer to the possibility of low iron, normal ferritin iron def. anemia
2. During 4 decades there were some substantial changes in the presenting symptoms, incidence,
serological performances, diagnostic criteria and epidemiology of CD. Please, refer to those
aspects.
3. Did in references 6, 16, 17 the authors measure CD cholesterol levels?
4. Frozen sera, for 4 decades,  could have lost sensitivity of antibodies titers. Did other markers
were included in order to check proteins titers reliability  during a so long period?
5. Is your population homogenous? Are there other Ethnicities (immigrants) that could have
impact the results?
Review for 10.1186/s12876-021-01667-y (2021)

Title: Symptoms and biomarkers associated with undiagnosed celiac seropositivity
Version: 3 Date: 15 Jan 2021
Reviewer's report:
I’ve read with interest the revised version of the manuscript entitled “Symptoms and biomarkers
associated with undiagnosed celiac disease”, which aims at assessing symptoms and biomarkers
associated with undiagnosed CD and could trigger testing for this disease.
Indeed, as well reported in the introduction, CD is heavily underdiagnosed and has significant
diagnostic delay. The strong point of the study is the large sample size. However, there is
a lack of novelty with regard to its objectives, as indications for CD testing according to
symptoms and laboratory changes are well known. Also, a major limitation of the paper is
considering CD diagnosis based on serology only, which is not in accordance with current
guideline recommendation; in this respect, the title, abstract and results are currently misleading
– they should all report on positive CD-related serology and not CD diagnosis.
Review for 10.1186/s12876-021-01667-y (2021)

Title: Symptoms and biomarkers associated with undiagnosed celiac seropositivity
Version: 5 Date: 13 Feb 2021
Reviewer's report:
Agree with the argument on population-based testing. Change of the phrasing from "CD
diagnosis" to "CD seropositivity" now accurately reflects the methods and results of the research.
Congrats!
Review for 10.1186/s12876-021-01653-4 (2021)

Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 1 Date: 16 Nov 2020
Reviewer's report:
In this small retrospective cohort study 12 patients with AS-AIH are described on clinical
characteristics, histology and short term prognosis. No control group was included. AS-AIH is
a rare presentation of AIH which can be a challenge to diagnose and treat.
I have some comments regarding this study
1) Patients with underlying cirrhosis were excluded from the present study but form part of the
population of AIH that present with coagulopathy. How many patients with underlying cirrhosis
were excluded from the study? For treating physicians this is a relevant population.
2) How many patients presented with encephalopathy (AS-AIH with acute liver failure
according to a recent review by Rahim et al. Liver Transplantation 2019)
3) In the article is commented on the prevalence of seronegative AIH in AS-AIH. In the
introduction and discussion it is mentioned as a feature that occurs more often in AS-AIH. In
the present study it was around 25% of patients. No control group of AIH patients were included
and in chronic presentation up to 34% of seronegative AIH was reported according to reference
17. I’m not sure if it is occurring more often in AS-AIH patients
4) All liver biopsies were revised and only 3 patients had interface hepatitis. Interface hepatitis
is a hallmark feature of AIH and present in all scoring systems. Do you have an explanation why
interface hepatitis was present in so few patients?
5) Two patients with pour outcome are described were the interval between symptoms and
treatment initiation was 60 and 70 days. At what timepoint are de baseline characteristics of
these patients in table 1 taken? Is there an explanation for the diagnostic delay in these patients?
6) The authors state that treatment with steroids is not proven effective in AS-AIH. But the
important question currently discussed in literature is if patients need to be treated with steroids
or immediately screened for liver transplantation as high corticosteroids before treatment can
cause high risk of infections after transplantation. Was liver transplantation evaluated as an
option for these patients?
7) Treatment effect was evaluated after 3 days. This is a very short period in comparison to the
available literature who advise to evaluate treatment between 7-14 days. Also I don’t understand
the decision to stop steroid treatment without evaluation for liver transplantation. If AIH and
AS-AIH if left untreated at all, the risk of mortality is very high.
8) Were patients also treated with azathioprine?
9) Disease relapse was reported in 1 patient. Without knowledge on steroid or treatment
withdrawal in all patients the interpretation of this data is difficult. Almost all AIH patients
develop relapse if treatment is stopped completely.
10) The authors have missed some relevant recent articles in the discussion including Anastasiou
et al 2018 Digestion; Zachou et al. 2019 Hepatology Research; Fujiwara et al. 2019 Liver
Transplantation; Biewenga et al. 2020 Liver Transplantation
Review for 10.1186/s12876-021-01653-4 (2021)

Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 2 Date: 22 Dec 2020
Reviewer's report:
Thank you very much for your answers on the questions and the revision of the article.
1. The 70% of patients with underlying cirrhosis that were excluded are relevant populations
to treating physicians. You should add this information to the article, so that readers better
understand which subpopulation you are studying.
2. Please add the data regarding encephalopathy to the article.
3. Please add your explanation regarding the low frequency of interface hepatitis to the article.
4. Please add to the article which patients were screened and listed for liver transplantation and
which moment.
Review for 10.1186/s12876-021-01653-4 (2021)

Title: Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Version: 3 Date: 04 Jan 2021
Reviewer's report:
Thank you for adding the data
One small comment: in the methods section you added that 70.7% of patients were excluded
due to cirrhosis, but 29 / 70 is +- 40% instead of 70%
Review for 10.1186/s12876-021-01678-9 (2021)

Title: CDX2 and Reg IV expression and correlation in gastric cancer
Version: 2 Date: 07 Nov 2020
Reviewer:  Fan-biao Kong
Reviewer's report:
1. it's better to prove that Reg IV promote cell migration and invation.
2. it would be easier to be accepted if you specify the relationship between CDX2 and Reg IV.
does CDX2 directly affect Reg IV, or there is other gene in the pathway between CDX2 and
Reg IV?
3. in the Method part, you designed Chemically synthetic siRNAs for human CDX2, Reg IV.
but in the Results, you presented CDX2 overexpressed and downregulated respectively. did you
silencing CDX2 and Reg IV in the same time? or by several times?
Review for 10.1186/s12876-021-01678-9 (2021)

Title: CDX2 and Reg IV expression and correlation in gastric cancer
Version: 2 Date: 27 Nov 2020
Reviewer's report:
This manuscript by Chai et al explored the role of CDX2 and RegIV in gastric cancer. This
manuscript is well written and for the most part, very clear. Assuming the queries I have listed
below can be addressed and the manuscript revised accordingly in the next iteration I would
recommend this manuscript for publication
1. For the experiments in Fig 2 different siRNA’s were used for the functional assays. These
were selected due to maximal knockdown in that cell line. Can the authors elaborate on the
justification for this? Surely it would make more sense to run both siRNA for both cell lines to
rule out off target effects of the construct.
2. Can the authors include information on how many times each experiments were performed?
Biological and technical replicates?
3. Many of the p values appear as p=0.000 can the authors revise these to include significant
figures
4. The right hand panel graphs in Fig4 state that relative protein concentration is given. What
is the data relative to?
5. The western blot images in Fig 4b are of poor quality. Do the authors have better ones?
6. Did the authors check for any effect of knockdown (or upregulation) of RegIV or CDX2
on proliferation or apoptosis? If such effects were to exist they may have an influence on the
invasion and migration results (e.g. additional cells due to increased proliferation might be
misinterpreted as increased invasion)
7. On the same note from looking at the data in figs 2 and 4 both cell lines chosen do not appear
to express RegIV at very detectable levels and MKN25 does not appear to express CDX2 at
detectable levels. Can the authors explain their justification for using them in the knockdown
experiments? Whilst they are ideal candidates for overexpression it doesn’t make sense to knock
down expression of a gene that barely expresses the protein of interest.
Review for 10.1186/s12876-021-01678-9 (2021)

Title: CDX2 and Reg IV expression and correlation in gastric cancer
Version: 5 Date: 01 Feb 2021
Reviewer:  Fan-biao Kong
Reviewer's report:
We have literally reviewed the manuscript named “CDX2 and Reg IV expression and correlation
in gastric cancer”, and believed that this study has an advantage of novelty and reliability.
Therfore, we command to accept.
Review for 10.1186/s12876-021-01678-9 (2021)

Title: CDX2 and Reg IV expression and correlation in gastric cancer
Version: 5 Date: 10 Feb 2021
Reviewer's report:
I think the authors have addressed the comments well and am happy to recommend this
manuscript for publication pending a couple of very minor issues which would benefit the
manuscript.
It might help future readers if some of the explanation was integrated into the text. I suspect
future readers may have the same questions. This is specifically referring to comments: 1 and 4
(simply explaining that its relative to beta actin in the legend would be sufficient)
I still have concerns about the Western blots representing the CDX2 protein for Figs 4 b. The
full blots now added as a supplementary file do not give much additional information. It would
be more convincing for me if a positive control sample could have been run alongside (perhaps
a sample from blot 4a (AGS cells which clearly expresses this protein at high levels)). Do the
authors have such a blot?
Similarly the same concerns exist for some of the RegIV blots appearing in the main figs. In this
case however the supp figures are better and could be used to try and obtain better resolution
images for the main figs. Specifically, the image for RegIV staining in fig 4a seems much less
clear than the full blot from the same fig (Supp 2a) and the same for RegIV staining in 4b which
also is clearer in Supp Fig 2c).
Review for 10.1186/s12876-021-01654-3 (2021)

Title: The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic
abnormalities in Brazilian patients with chronic hepatitis C
Version: 1 Date: 04 Dec 2020
Reviewer's report:
The study reports the association of two common steatogenic variants in the genes PNPLA3
and TM6SF2 with liver disease in 365 Brazilian patients with HCV, and 134 controls. Liver
disease was evaluated by histology. The main finding was that neither variant was associated
with increased steatosis or fibrosis in the cohort.
Comments
1. Please state in the abstract that steatosis and fibrosis were evaluated by histology.
2. It would be interesting to see associations for a combined risk score (PNPLA3 + TM6SF2).
3. How many had missing covariates? It seems from Table 1 that the dataset was almost
complete, with only a few missing information on some of the covaraites. Please add a statement
to this effect (ie. what was the max % of missing values for any covariate?) in the Methods
section.
4. the number of significant digits in numbers is excessive, throughout the manuscript (both
in the text and tables). Ie. percentages could be rounded to 1 digit after the period (instead of
30.49%, just use 30.5%), 'TM6SF2 and PNPLA3 heterozygosity were 0.1977 and 0.5608' should
be 0.20 and 0.56. P-values could be reported with 3 significant digits after the period. Ie. 0.044
instead of 0.0443. ORs should be with 2 digits after the period: '1.95, 95% CI 1.01-3.79' instead
of '1.9531 .953, 95% CI 1.009-3.788'.
5. The moderate sample size (and consequently low power) should be mentioned as a limitation.
6. The nucleotide position for the TM6SF2 variant is c.499C>T and not c.449 as stated
throughout. Please correct.
Minor
1. page 4 line 19: 'The wild allele (C allele)' , better: 'the common C allele'
2. Page 4, line 21: delete 'the' in front of TM6SF2.
3. page 13, line 13: 'PNPLA3 gene was not in Hardy-Weinberg equilibrium, what precludes firm
conclusions'. 'what' should be 'which'.
Review for 10.1186/s12876-021-01654-3 (2021)

Title: The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic
abnormalities in Brazilian patients with chronic hepatitis C
Version: 2 Date: 27 Dec 2020
Reviewer's report:
My previous comments have been addressed.
Regarding the association of the combined PNPLA3 + TM6Sf2 score: the section in the result
section on this is unclear (page 12, line 13):
'The HCV genotype was not associated with any of the liver histology parameters evaluated,
neither with the combination of TM6SF2 and PNPLA3 polymorphisms on logistic regression
analyses (significant liver fibrosis: p = 0.079; liver steatosis: p = 0.161). '
This reads as if you tested HCV genotype versus the TM6SF2+PNPLA3 combined score... but
this cannot be right? please clarify. Should it be:
'The HCV genotype was not associated with any of the liver histology parameters evaluated.
Likewise, the combination of TM6SF2 and PNPLA3 was not associated with liver fibrosis or
steatosis (p = 0.079 and p = 0.161, respectively).'
?
Review for 10.1186/s12876-021-01655-2 (2021)

Title: Risk Indices Predicting Graft use, Graft and Patient Survival in Solid Pancreas
Transplantation: A Systematic Review
Version: 0 Date: 26 Jan 2021
Reviewer's report:
Thank you for the privilege of reviewing your manuscript. It is a well written systematic review
on risk indices for pancreas transplantation. I have some concerns, however, about the database
search strategies:
1. keywords for pancreas transplantation can be more sensitive, such as pancreas adj3
transplant*.mp. This would ensure not missing relevant citations.
2. There are some irregularities in how the search sets were combined. For example in the
Embase search you OR together lines 1 through 6, but then don't use that line in your result set.
A similar problem is seen in your Medline search.
3. When searching for risk indices it would have been better to use a validated
search filter such as the filter for clinical prediction guides from the Health Information
Research Unit at McMaster University: Wong SS, Wilczynski NL, Haynes RB,
Ramkissoonsingh R. Developing optimal search strategies for detecting sound clinical
prediction studies in MEDLINE. Proc AMIA Symp. 2003;:728-32. https://hiru.mcmaster.ca/
hiru/hiru_hedges_medline_strategies.aspx#ClinicalPredictionGuides
Review for 10.1186/s12876-021-01655-2 (2021)

Title: Risk Indices Predicting Graft use, Graft and Patient Survival in Solid Pancreas
Transplantation: A Systematic Review
Version: 0 Date: 26 Jan 2021
Reviewer's report:
The authors aimed to perform a systematic review of studies deriving and validating risk models
for pancreas transplant outcomes.  They found the majority of studies related primarily to
two risk indices: the P-PASS and the PDRI.  The P-PASS is a measure of surgeon behaviour
and determines the likelihood that a procured pancreas will be discarded based on donor
organ characteristics.  The PDRI is a model based on mostly donor demographic features and
determines the risk of 1 year graft failure in relation to that of the median donor.
Risk model deriving studies often did not report a discrimination statistic, or when reported
showed relatively poor discrimination.  The authors concluded that both P-PASS and PDRI have
been externally validated in specific populations but the quality of the studies was poor and
existing evidence does not allow extrapolation to further populations, specifically to the New
Zealand and Australian population.  The authors comment on the challenge of validating the
model in their population due to differences in covariate coding.
The authors have undertaken a large and time-consuming project and should be commended for
their efforts.  While neither model is used commonly in clinical practice, even in the populations
where it has been validated, the findings of this study do add to the literature.
Review for 10.1186/s12876-021-01668-x (2021)

Title: Functional outcomes of patients with short-segment Hirschsprung disease after transanal
endorectal pull-through
Version: 1 Date: 17 Jan 2021
Reviewer:  Mario Trombetto
Reviewer's report:
I would like to congratulate authors for this precise paper on a very difficult issue. I need to give
only some suggestions to improve the quality of the study.  The keywords are very aspecific
and must be better chosen (eliminating sex, prognostic factors, functional outcome..). You must
better specify postoperative complications: it is really insufficient to say complications yes or
no... becasuse clearly the type and sverity of complcations (abscesses, anastomotic dehisence,
stricture ecc) influence the functional outcome of the patients. I hope the tables will be better
described.
Review for 10.1186/s12876-021-01668-x (2021)

Title: Functional outcomes of patients with short-segment Hirschsprung disease after transanal
endorectal pull-through
Version: 1 Date: 23 Jan 2021
Reviewer:  Emre Sivrikoz
Reviewer's report:
The study reported functional outcomes in an undefined time-interval. The authors should clarify
which time point of their functional outcome assessment is based upon, preferably a median
time interval. In the current version, it is confusing whether they are reporting short or long term
outcomes, or perhaps mixed.
Review for 10.1186/s12876-021-01668-x (2021)

Title: Functional outcomes of patients with short-segment Hirschsprung disease after transanal
endorectal pull-through
Version: 1 Date: 24 Jan 2021
Reviewer:  Ugo Grossi
Reviewer's report:
- Abstract
-- ""multivariate analysis showed sex was significantly associated with VBM..."; please add the
word "male" prior to "sex" as appropriate
- Methods
-- "The TEPT was performed by three pediatric surgeons with various experiences in our
institution." It is crucial to add details on surgeons' experience in terms of no. of cases already
performed by each of them, as this will be later acknowledged by the Authors as potential source
of bias among Limitations.
-- "Statistical analysis". Please add details on the statistical software used.
- Results
-- "We examined 55 medical records". Were patients recruited consecutively?
- Please add third decimal to all P values consistently throughout the manuscript.
- Please avoid judgements on the Results by avoiding the use of adverbs (e.g. "Interestingly,
multivariate analysis showed...").
Review for 10.1186/s12876-021-01668-x (2021)

Title: Functional outcomes of patients with short-segment Hirschsprung disease after transanal
endorectal pull-through
Version: 1 Date: 25 Jan 2021
Reviewer:  Iacopo Giani
Reviewer's report:
INTRODUCTION
In the introduction, reference is made to transabdominal pull-through but this is not used as a
term of comparison in a clinical comparison in the context of the study.
METHODS and RESULTS
The study does not indicate the follow-up to which patients are re-evaluated, the pre-operative
status in functional terms (bowel movement) is not clear and even subsequently in the results
if between a first follow up and perhaps a second longer follow up differences. In the absence
of the pre-operative data in functional terms, the possible progonostic function of this data on
the intervention is also missing.
The study is well conducted, the data collection well done and I would speak more of a
prospective maintained database as a reward for those who have prospectively collected data
over the years (unfortunately remaining a retrospective work). The statistical analysis I would
say is very well conducted.
It could be useful to include in the study a small flowchart on the measures adopted for a
successful intervention in terms of complications and in functional terms, to be discussed in the
discussion
In summary I think the study is interesting and well written, if it were possible to have the data
requested in my comment as well as the flowchart I believe it would acquire in terminality. Well
done!
Review for 10.1186/s12876-021-01659-y (2021)

Title: Impact of improvement of sleep disturbance on symptoms and quality of life in patients
with functional dyspepsia
Version: 0 Date: 26 Nov 2020
Reviewer's report:
REVIEWER BLIND COMMENTS TO AUTHOR:
Submission ID: 759ab808-1a2f-47a2-b3f0-0c93c56f4d70
Title: Impact of improvement of sleep disturbance on symptoms and quality of life in patients
with functional dyspepsia
Journal: BMC Gastroenterology
1) The authors did not demonstrate how they calculated the sample size.
2) Could have an effect of gender as well as menopause on the findings?
3) The study has approximately 4% of references from the last three years, none of which after
2019. Please update it.
4) The statistical tests performed by the authors are superficial. Binary logistic regression is
recommended to assess the association between the factors.
5) The figure could have been shown as a boxplot.
Review for 10.1186/s12876-021-01658-z (2021)

Title: EXTRA-ESOPHAGEAL SYMPTOMS IN INDIVIDUALS WITH AND WITHOUT
EROSIVE ESOPHAGITIS: A CASE-CONTROL STUDY IN ALBANIA
Version: 2 Date: 17 Dec 2020
Reviewer:  Vincenzo Savarino
Reviewer's report:
The Authors have diagnosed reflux esophagitis using the well known Los Angeles classification,
but the majiority of their cases pertained to the mild degrees of this disease (A and B). According
to the recent Lyon Consensus, these degrees do not permit to diagnose reflux esophagitis with
certainty because of great interobserver variability among endoscopists. So, a more precise
diagnosis by means of functional tests should have been made, but there is no mention of this
kind of examinations in this study.
It is well known that reflux esophagitis is present in a small part of patients with extra-esophageal
symptoms (< 30%) and therefore endoscopy has a poor sensitivity to detect GERD in these cases.
Respiratory symptoms can be due to many diseases beyond GERD. Did the Authors exclude
other causes for these extra-esophageal symptoms (e.g. the use of ACE inhibitors for chronic
cough) ?
The majority of GERD patients pertain to the NERD population without erosive esophagitis. It
would have been more interesting to compare the rate of extra-esophageal symptoms between
NERD and erosive patients.
The table comparing findings between the mild and severe forms of esophagitis can be omitted,
because patients with grades C and D were much lower for a meaningful statistical comparison.
The study was carried out more than six years ago. Is there any reason for the delay in the
preparation of this paper ?
Review for 10.1186/s12876-021-01658-z (2021)

Title: EXTRA-ESOPHAGEAL SYMPTOMS IN INDIVIDUALS WITH AND WITHOUT
EROSIVE ESOPHAGITIS: A CASE-CONTROL STUDY IN ALBANIA
Version: 2 Date: 04 Jan 2021
Reviewer's report:
This study aimed to assess the prevalence of extra-esophageal symptoms in individuals with and
those without erosive esophagitis, and elucidate independent factors related to the development
of extra-esophageal manifestations.
1) In method section (study design and data collection), the sentences regarding the informed
consent and ethical approval appeared twice (p.5, l.56-58, p.8, l.117-118).
2) In method section (study population), the authors stated that “two controls for each case were
targeted for recruitment among family members of the patients”. However, it should be clearly
mentioned how they were selected (the controls were selected among siblings or cousins who
were close in age?)
3) In result section, the number should be correctly rounded to the nearest whole number:
5.5%=6% (p.9, l.145), 60.4%=60% (p.9, l.147), 23.1%=23% (p.9, l.149), 2.75=2.8 (p.9, l.157).
4) Typographical errors
- “throat cleaning” appears in the manuscript several times, but it should be “throat clearing”.
- “controls s without” should be “control without” (p.11, 211)
Review for 10.1186/s12876-021-01651-6 (2021)

Title: Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic
anastomotic leakage following transthoracic esophageal resection
Version: 3 Date: 23 Nov 2020
Reviewer's report:
Thanks for the opportunity to review good article.
This study focused on intrathoracic anastomotic leakages after esophageal resection.
EVT is a feasible and safe procedure for anastomotic leakage. However not enough research
has been done.
This study was conducted with a large number of patients, resulting in sufficiently meaningful
results.
Review for 10.1186/s12876-021-01651-6 (2021)

Title: Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic
anastomotic leakage following transthoracic esophageal resection
Version: 3 Date: 27 Nov 2020
Reviewer:  Jun Cheul Park
Reviewer's report:
The authors evaluate the feasibility, effectiveness, and safety of EVT for intrathoracic
anastomotic leakage following transthoracic esophageal resection.
The manuscript is well written and would be helpful for the clinician to understand the efficacy
and safety of EVT.
I have some questions about this study as follows.
1. This study was evaluated based on prospectively collected data, and retrospective analysis.
Therefore, authors should clearly state whether this study is prospectively registered.
Since the abstract is described as follows, it may confuse readers whether this is a prospective
study or not.
‘This prospective, single-center study aimed to evaluate the feasibility, effectiveness, and
safety of EVT for intrathoracic anastomotic leakage following abdomino-thoracic esophageal
resection. ‘
2. In this study, stent or EVT was selected as the first endoscopic treatment after a leakage. What
was the criterion for choosing between these two endoscopic methods?
3. It would be better to simply add the process of esophageal diversion in method section.
4. According to leakage size grade, over 60% was small defect. Do these small cases really need
an EVT? I think these cases can be treated with clip or stent.
And the large sized defect which can maximize EVT effect was only 12.7%.
5. In page 11, “four patients with a therapeutic switch to EVT after failure of the SEMS
treatment”
What was the reason for SEMS failure? Please clarify whether it failed due to SEMS
complications (migration, ulcer etc.) or just because of incomplete healing.
Review for 10.1186/s12876-021-01651-6 (2021)

Title: Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic
anastomotic leakage following transthoracic esophageal resection
Version: 5 Date: 23 Dec 2020
Reviewer's report:
The authors evaluated the feasibility, effectiveness, and safety of EVT.
The Manuscript is well written and good enough for the physician to understand EVT.
Review for 10.1186/s12876-021-01651-6 (2021)

Title: Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic
anastomotic leakage following transthoracic esophageal resection
Version: 5 Date: 26 Dec 2020
Reviewer:  Jun Cheul Park
Reviewer's report:
All points pointed out by the reviewers have been addressed satisfactorily.