JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-024-03569-1 (2024)

Title: Construction and validation of a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage
Version: 3 Date: 04 Nov 2024
Reviewer's report:
This paper aims to construct and validate a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage (EGVH) and compares it with existing scoring
systems such as GBS and pRS. Based on retrospective clinical data from 265 patients, the study
constructs a model using binary logistic regression and validates its predictive ability through
metrics like ROC curves and AUC. While the study holds clinical significance, several aspects
require improvement.
1. Methodology
Sample Size: This is a single-center retrospective study with a relatively small sample size (265
patients), which may impact the model’s external validity. It is recommended that future studies
include larger, multi-center prospective trials to further validate the model's stability and broader
applicability.
Factor Selection: The study excluded certain conventional factors, such as hemoglobin levels,
from the model and instead chose transfusion requirements as a predictive factor. While this is
justifiable, the rationale appears somewhat weak. It is recommended to provide more literature
support for this decision in the discussion.
2. Data Analysis
The paper handles data meticulously, using R software for data cleaning, feature selection, and
model validation, which is in line with standard statistical methods. However, some important
metrics, such as sensitivity (0.40), are relatively low, which may affect the model's practical
prediction performance. It is advised to explore ways to enhance the sensitivity of the model
while retaining its high specificity (0.936).
3. Discussion and Conclusion
The discussion section covers most relevant points, noting the limitations of existing scoring
systems and highlighting the advantages of the new model. However, there is not enough
in-depth discussion on the clinical applicability and future research directions, particularly
concerning the model’s adaptability and limitations across different patient populations or
conditions. It is suggested to expand on these points, especially on potential challenges in
applying the model in real-world settings.
My recommendation to this article is accept after minor revision.
Review for 10.1186/s12876-024-03569-1 (2024)

Title: Construction and validation of a predictive model for the risk of rebleeding in patients
with esophageal and gastric varices hemorrhage
Version: 4 Date: 17 Nov 2024
Reviewer's report:
Thank you for re-submitting the manuscript. I have carefully reviewed the authors  revisions and
responses, and I am satisfied with the changes made. I have no further comments or concerns.
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 5 Date: 24 Nov 2024
Reviewer:  Mohamad Iskandarani
Reviewer's report:
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 5 Date: 25 Nov 2024
Reviewer:  Ronald Mbiine
Reviewer's report:
Thank you authors on writing this manuscript.
I enjoyed reading your manuscript and found it informative and well written.
I believe it will be highly informative to various readers.
The main concerns that I have are in the methodology:
1. This being a predictive study, there needed to be clarity on how you derived your sample size.
Do you believe your study was sufficiently powered to derive the conclusions above?
2. How did you deal with the missing data and were there adjustements to account for this?
3. Could you also describe other details of your study methods including the study setting,
population etc..
4. A few typing errors that can be corrected.
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 5 Date: 26 Nov 2024
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
This manuscript provides a thorough analysis of the study on acute cholangitis, with a clear
focus on inflammatory and nutritional biomarkers. The findings are compelling and supported
by statistical evidence.  However, i have some points to clarify:
1. The exclusion of patients with prior antibiotic treatment might introduce selection bias.
Consider discussing how this could influence the generalizability of the findings.
2. The inverse relationship of PNI and Albumin with disease severity is interesting. Discuss
why these markers are physiologically relevant to acute cholangitis severity and if other studies
corroborate this finding.
3. Some of the evaluated biomarkers were analyzed in this recent article (https://doi.org/10.3390/
medicina60111854). I suggest to cite it in the Discussion section.
4. Table 2 and Table 3: consider combining these into one table summarizing univariate and
multivariate analysis results to streamline the manuscript.
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 03 Dec 2024
Reviewer:  Mohamad Iskandarani
Reviewer's report:
Dear Authors,
Thank you for addressing the previous comments, the manuscript is well-formulated . I have
added some minor comments in the manuscript mainly in the limitations section.
Best of Luck
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 03 Dec 2024
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
Thank you for your revisions. The manuscript has been improved.
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 03 Dec 2024
Reviewer's report:
I evaluated this study with my nearly 6000 ERCP subjects and cholangitis management
experience. The primary approach in cholangitis treatment should be directed at etiology. I
think that evaluating various biochemical results will not be very useful in cholangitis treatment.
Therefore, I do not find this study appropriate.
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 06 Dec 2024
Reviewer:  Mohamed El Ghobary
Reviewer's report:
now the article is ready for publications after the amendements
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 09 Dec 2024
Reviewer:  Ronald Mbiine
Reviewer's report:
Dear authors,
Thank you for the improvements that you have made in this work.
You have adequately addressed the concerns that were earlier raised in the earlier review.
Best regards
Review for 10.1186/s12876-024-03560-w (2024)

Title: Predicting Severity of Inpatient Acute Cholangitis : Combined Neutrophil-to-
Lymphocyte Ratio and Prognostic Nutritional Index
Version: 6 Date: 09 Dec 2024
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Re: "Predicting Severity of Inpatient Acute Cholangitis: Combined Neutrophil-to-Lymphocyte
Ratio and Prognostic Nutritional Index"
Your manuscript offers an insightful and clinically valuable contribution to understanding and
predicting the severity of acute cholangitis. By integrating inflammatory markers like NLR and
SII with nutritional indices such as PNI and albumin, you propose a practical and effective
Prognostic Nutritional Score (PNS) for clinical stratification.
The revisions made to the manuscript address the feedback provided. The improvements in
the methodology section, particularly regarding the inclusion/exclusion criteria, strengthen the
study’s transparency. Additionally, the discussion contextualizes the findings, particularly the
clinical implications of PNS and its potential integration into routine care.
Strengths
The study introduces an easy-to-use scoring system that can enhance decision-making in acute
cholangitis management.
The methodology and statistical analysis are sound, ensuring robust results.
Clear and well-organized tables and figures effectively communicate the data.
Thank you for your comprehensive response to previous feedback and for this important
contribution to the field of hepatobiliary medicine.
Sincerely,
Review for 10.1186/s12876-024-03561-9 (2024)

Title: Effects of probiotics in elderly hospitalized tube-fed patients with antibiotics use
Version: 3 Date: 25 Sep 2024
Reviewer's report:
Abstract
- Methods: change the highlighted verb from singular to plural in the excerpt: "the probiotics
WAS continued to use for an additional 7 days after completion of antibiotics therapy";
- Results: change the highlighted word from singular to plural in the excerpt: "11 patients
completed the study in both GROUP";
- Conclusion: according to the Results, there was a significant difference in the stool frequency
for the probiotic group. No significant differences were found in the stool form. This only
occurred during the follow-up period (4 weeks), but this is not clear in the Conclusion, causing
confusion.
Text
- Methods: change the highlighted word from singular to plural in the excerpt:  "Both GROUP
had patient who failed to complete the study either due to the use of antibiotics for more than
14 days or personal reasons.";
-- In the "Data collection" subsection did not describe which data were collected within each
category: anthropometric, laboratory, medication, and nutrient intake. Therefore, it is impossible
for the study to be repeated;
-- In the "Statistical methods" subsection, the power of the test was very low, not reaching the
minimum recommended in the literature, which is 0.8 or 80%. I suggest looking in the literature
for a justification to further support the relevance of the results found.;
- Results:  This excerpt should be rewritten to conform to the formal norms of the English
language: "There were no significant differences were observed in baseline characteristics
between the two groups". Suggestion: "There were no significant differences in baseline
characteristics between the two groups";
-- This excerpt does not present the data that confirms your statement: "During the follow-up
period of the probiotic group (a total of 4 weeks), the stool form significantly differed compared
to both the beginning and end of antibiotics therapy";
- Discussion: change the highlighted word from singular to plural in the excerpt:"We found that
the PATIENT in both groups were moderate malnutrition risk as both have a score over 3";
-- This excerpt should be rewritten to conform to the formal norms of the English language:
"Increasing amount of evidences indicates that critical illnes...". Suggestion:  "A growing body
of evidence indicates that critical illnes...";
-- Change the highlighted word from plural to singular in the excerpt: "Lastly, we didn’t design
the comparison between different compositions or dosages of the PROBIOTICS strains.";
- Conclusion: the Conclusion needs to be rewritten to agree with the Objectives of the study, as
it does not provide any conclusions regarding nutritional status.
In addition, the Conclusion is about the prolonged effects of the probiotic after the end of
antibiotic treatment, but this is not clear and the information seems to be about the effects of the
probiotics during antibiotic use, which influences stool frequency and not stool form.
Review for 10.1186/s12876-024-03561-9 (2024)

Title: Effects of probiotics in elderly hospitalized tube-fed patients with antibiotics use
Version: 3 Date: 01 Oct 2024
Reviewer's report:
- Small sample size
- The use of probiotics during antibiotic therapy is not effective because the bacteria are not
antibiotic resistant.
. The use of probiotics should normally be prolonged for at least 30 days after the end of antibiotic
therapy.
- There are no indications on the type of enteral mixture (standard, semi-elemental, with or
without fibers, etc.) used in the two patient populations.
Review for 10.1186/s12876-024-03561-9 (2024)

Title: Effects of probiotics in elderly hospitalized tube-fed patients with antibiotics use
Version: 5 Date: 28 Oct 2024
Reviewer's report:
-It is expected that more references will be made in the discussion section on the mechanism of
interaction between probiotics and antibiotics.
-No data from nutritional intake surveys except NRS were completed for patients other than
preterm? Dietary intake can significantly affect outcomes.
-The results table refers to blood sample analyses (such as Cr, CRP…), while this is not
mentioned in the methods section.
-It seems that a precise reference to the necessity of doing the work and why the study was
conducted, especially in this age group, is needed in the introduction.
Review for 10.1186/s12876-024-03554-8 (2024)

Title: Efficacy and Safety of PD-1 and PD-L1 Inhibitors in Advanced Colorectal Cancer: A
Meta-Analysis of Randomized Controlled Trials
Version: 2 Date: 11 Oct 2024
Reviewer's report:
Dear Editor, thank you so much for inviting me to revise this manuscript.
This study addresses a current topic in colorectal cancer.
The manuscript is quite well written and organized. English could be improved.
Figures and tables are comprehensive and clear.
The introduction explains in a clear and coherent manner the background of this study.
We suggest the following modifications:
• Introduction section: although the authors correctly included important papers in this setting,
we believe the evolving systemic treatment scenario of cancer IO in solid tumors including
colorectal cancer and predictors of response / resistance should be further discussed and some
recent papers added within the introduction ( PMID: 38791914 ;  PMID: 36064585;PMID:
37819422; PMID: 35029519; PMID: 32762027 ), only for a matter of consistency. We think it
might be useful to introduce the topic of this interesting study.
• Methods and Statistical Analysis: nothing to add.
• Discussion section: Very interesting and timely discussion. Of note, the authors should expand
the Discussion section, including a more personal perspective to reflect on. For example, they
could answer the following questions – in order to facilitate the understanding of this complex
topic to readers: what potential does this study hold? What are the knowledge gaps and how do
researchers tackle them? How do you see this area unfolding in the next 5 years? We think it
would be extremely interesting for the readers.
However, we think the authors should be acknowledged for their work. In fact, they correctly
addressed an important topic , the methods sound good and their discussion is well balanced.
One additional little flaw: the authors could better explain the limitations of their work, in the
last part of the Discussion.
We believe this article is suitable for publication in the journal although major revisions are
needed. The main strengths of this paper are that it addresses an interesting and very timely
question and provides a clear answer, with some limitations.
We suggest a linguistic revision and the addition of some references for a matter of consistency.
Moreover, the authors should better clarify some points.
Review for 10.1186/s12876-024-03546-8 (2024)

Title: Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of
the Notch signaling pathway
Version: 3 Date: 26 Sep 2024
Reviewer's report:
This article is a study on the therapeutic effect of Sinomenine hydrochloride (SH) on ulcerative
colitis (UC) in mice. The article provides detailed information on experimental design, methods,
results, and discussion. Here are some potential issues and shortcomings:
1. Sample Size: The study used 24 mice, with six in each group. While this is a common sample
size for preliminary studies, a smaller sample may affect the statistical power and extrapolation
of the results.
2. Randomization and Blinding: The article does not clearly state whether randomization and
blinding were used in the experiment. These measures help reduce experimental bias and
subjectivity.
3. Dose Selection: The study used two dose levels of SH (20 mg/kg and 60 mg/kg) but did not
provide a detailed basis for dose selection. Ideally, doses should be chosen based on previous
literature or dose-response studies. Exploring a wider range of dosages could provide a more
comprehensive understanding of the dose-response relationship and optimal therapeutic dose.
4. Long-term Effects and Safety: The study only observed short-term therapeutic effects and did
not assess the potential side effects and safety of long-term use of SH.
5. Mechanism Exploration: Although the article suggests that SH may treat UC by inhibiting
the Notch signaling pathway, the exploration of the mechanism may not be in-depth enough.
Further investigation is needed to elucidate the detailed molecular mechanisms.
6. Clinical Relevance: The study was conducted in an animal model, and whether its results can
be directly translated to human patients requires further clinical research for verification.
7. Interpretation of Results: The results in the article need to be interpreted cautiously. For
example, although SH reduced the levels of inflammatory factors, the article did not directly
prove that this was achieved through the Notch signaling pathway.
8. Lack of Comparison with Standard Treatments: The study does not compare SH with existing
standard treatments for UC. Such comparisons would be valuable to position SH in the context
of current therapeutic options.
If the above issues can be adjusted, please make the modifications directly in the manuscript. If
they are difficult to adjust, it is recommended to explain in the Limitations section.
Review for 10.1186/s12876-024-03546-8 (2024)

Title: Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of
the Notch signaling pathway
Version: 3 Date: 11 Oct 2024
Reviewer's report:
Interesting story, but generally information is small, just showing partial response to DSS-
induced colitis. Adding in vitro functional analysis of sinomenine would be better.
Review for 10.1186/s12876-024-03546-8 (2024)

Title: Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of
the Notch signaling pathway
Version: 3 Date: 02 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Title Rodents donot suffer from Uc but can developed colitis mimicing UC Thus UC model
should be better used Abstract Accodingly DSS colitis should be used and not UC! Abstract
Authors should provide numerical and p values for statistically significant relations Methods
Materials should be better presented on their first appearance in the experiment It is not clear in
which way intragastric infusion was performed Was a scale to record overt bleeding used? Was
number of imes rodents open their bowels recorded? DAI score should be better descibed as well
as CMDI Histology should be described in detail Also PCRs should be described in more detail
if possible Statistics Six subjests is a too small number to draw any conclusions Have authors
calculated power of the study or their survey is a preliminary one?  Results Authors should
provide numerical and p values for statistically significant relations in the text Any difference
between the two doses of SH should be reported Immunohistochemistry pictures could be also
included
Review for 10.1186/s12876-024-03546-8 (2024)

Title: Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of
the Notch signaling pathway
Version: 4 Date: 18 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Numerical values could be provided for statistical significant values apart from p-values
I woder whether have authors calculated power of the study? The sample is too small but the
results were statistical significant
Review for 10.1186/s12876-024-03546-8 (2024)

Title: Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of
the Notch signaling pathway
Version: 5 Date: 28 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
I think that all changes requested have been applied and the document is ready for publication
Thus it could be accepted
Review for 10.1186/s12876-024-03548-6 (2024)

Title: Impact of Nutrition Risk Index, Prognostic Nutritional Index and Skeletal Muscle Index
on early myelosuppression of first-line chemotherapy in stage IV gastric cancer patients
Version: 2 Date: 08 Aug 2024
Reviewer's report:
The paper provides very interesting data but it still needs a considerable revision
In this study, regimens of chemotherapy are not standardized. This study evaluated a mix of cases
treated with monotherapy (S-1/capecitabine) and doublet therapy (SOX/XELOX). Therefore, it
is unclear whether the myelosuppression is due to chemotherapy or nutritional status.
Furthermore, number of metastatic sits or presence of bone metastasis may affect the nutritional
status.
Authors should reanalyze after identifying these confounding factors.
Review for 10.1186/s12876-024-03548-6 (2024)

Title: Impact of Nutrition Risk Index, Prognostic Nutritional Index and Skeletal Muscle Index
on early myelosuppression of first-line chemotherapy in stage IV gastric cancer patients
Version: 3 Date: 07 Nov 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Yes, the authors have responded adequately to most of my raised
concerns. My only minor concern remaining refers to the diet of the patients and how this can
influence hemoglobin levels, presence of sarcopenia, BMI and others. I will come back to this
later in the next part of this evaluation.
They have made the changes in the manuscript and my overall impression is that this paper is
good and has a big potential to be accepted for publication
REQUESTED REVISIONS:
My only minor issue is the diet. Authors have written in the manuscript that all subjects came
from the same area and there they all ate a balanced diet, and their dietary habits were basically
the same and also that there was not a phenomenon of partial or picky eating. I would remove this
statement because it is impossible that all people eat the same no matter if they come from the
same area so this will only attract negative attention to the editor. Instead, I would recommend
the authors to list the lack of dietary records as a limitation of this study with the other limitations
that start on line 284.
ADDITIONAL REQUESTS/SUGGESTIONS:
It is important that the authors state the lack of dietary records as a limitation and also remove
the statement that all the diets were the same for all patients
Review for 10.1186/s12876-024-03548-6 (2024)

Title: Impact of Nutrition Risk Index, Prognostic Nutritional Index and Skeletal Muscle Index
on early myelosuppression of first-line chemotherapy in stage IV gastric cancer patients
Version: 3 Date: 14 Nov 2024
Reviewer's report:
In this study, regimens of chemotherapy are not standardized. As pointed out by past reviewer,
this study evaluated a mix of cases treated with monotherapy (S-1/capecitabine) and doublet
therapy (SOX/XELOX). Therefore, it is unclear whether the
myelosuppression is due to chemotherapy or nutritional status.
Authors should standardize the use to either a single agent regimen or doublet regimen. If
authors want to explore the relationship between pre-chemotherapy nutritional state and early
myelosuppression, the regimen should be standardized, because the significant different in the
frequency of myelosuppression between monotherapy and doublet therapy.
Review for 10.1186/s12876-024-03548-6 (2024)

Title: Impact of Nutrition Risk Index, Prognostic Nutritional Index and Skeletal Muscle Index
on early myelosuppression of first-line chemotherapy in stage IV gastric cancer patients
Version: 4 Date: 25 Nov 2024
Reviewer's report:
The manuscript has been much improved and is in a nice condition now.
As for the non-uniform regimens, it would be better to evaluate a grouping analysis for each
regimen, if possible.
However, I received the following opinion from the author.
Due to the small sample size, further grouping analysis of the chemotherapy regimen was
difficult.
Review for 10.1186/s12876-024-03547-7 (2024)

Title: Association between bowel movement frequency, stool consistency and NAFLD and
advanced fibrosis: NHANES 2005-2010
Version: 0 Date: 12 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Parameters evaluated could be presented Higher BMF definition should be provided
Methods Because NAFLD definition has been replaced with MAFLD definition should be
changes Moreover MetFLD and ALD should be excluded since alcojol consumption can affect
pancreatic function Actually authors are doing it in a non-systematic way and according to recent
classification Was lactition a period exluded or not? Numerical values for patients excluded
should be moved in the results section If available special reference should be done for fiber
consumption, devided in solable and non-solable as well as liquids daily consumption  especially
water Moreover comorbidities such as diabetes, parkinson disease or other neurological disease
that could affect bowel motility, in addition to opioids consumption,  should be included in the
analysis Results Because prediction of significant fibrosis based on nomograms is not as specific
it would be interesting to performed an analysis of patients with more robust diagnosis
Review for 10.1186/s12876-024-03547-7 (2024)

Title: Association between bowel movement frequency, stool consistency and NAFLD and
advanced fibrosis: NHANES 2005-2010
Version: 1 Date: 28 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Since the aim of the study is to evaluate the relation between bowel habits and liver
fibrosis in MAFLD MAFLD should be replaced by fibrosis in the results The same is valid for
the results Otherwise the paper is ready for publication if editors are ready to overlooked that
fibrosis evaluation is based on nomograms and no biopsy or radiological evaluation of liver
stiffness is available
Review for 10.1186/s12876-024-03547-7 (2024)

Title: Association between bowel movement frequency, stool consistency and NAFLD and
advanced fibrosis: NHANES 2005-2010
Version: 1 Date: 28 Nov 2024
Reviewer:  Amira A A Othman
Reviewer's report:
I want to extend my congratulations to all those involved in this work. All the required
amendments have already been made carefully and satisfactorily. I hope that the research will
be presented to science.
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 1 Date: 14 Jul 2024
Reviewer's report:
Overall, the authors propose that EPIYA motifs change over time, perhaps due to some changes
in the CagA gene. Furthermore, they reveal that the pathologies were not related to changes in
the patterns of EPIYA motifs. Overall, the research is interesting. My comments are listed below.
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 1 Date: 05 Aug 2024
Reviewer's report:
Ghadersoltani et al. have designed and executed a good study. It is also well written. The 10-
year follow-up study is a good addition to the field and shows how cagA genotypes change over
the course of an infection. This has implications in disease progression and surveillance.
However, I have concerns over the ethical approval for this project. It is not clear if the patients
were treated for H. pylori infection on initial detection of the bacteria. Please may the authors
provide clarification over these points and make it clearer how the study was designed in this
regard.
Tables have no legend – please add legends to all tables and figures.
Please may the authors add a discussion point around how cagA changes are occurring when
it is thought most patients are infected with a single strain that has diversified over time (i.e.
recombination changes in cagA are therefore unlikely in this condition). Do the authors believe
mixed infections could be driving genotype changes. Have the authors identified any patients
with a mixed strain infection (such as isolates with multiple genotypes or selecting multiple
single colony isolates to screen per patient).
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 1 Date: 13 Aug 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear authors
Ethical approval should be provided
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 3 Date: 28 Aug 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
changes are done , accepted for publication.
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 3 Date: 13 Sep 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Percentages should be given apart from crude numbers Risk factors for change cag A
pattern through gastritis evolution should be given before reporting connection of those changes
with clinical presentation and pathology  Methods Definition of dyspepsia should be provided
at least as a reference Preferably Rome IV criteria should have been applied or definition
could be adapted if data are available A standard scale to weight dyspetic symptoms should
have been used Use of PPIs should also be an exclusion criterion Also H. pylori eradication
during the follow-up period  Also collection of data affecting H. pylori could be collected
and  evaluated as a possible risk factor for CagA motif evolution Smoking habits and alcohol
cosumption definitions should be provided Data on study population demographics belong to
the results session Biopsies from gastric corpus and incisura should have been taken according
to Sidney protocol Thus gastric pathology cannot be properly evaluated based only to antral
biopsies Moreover since atrophic gastritis starts for the antrum and incisura H. pylori status can
be misjudjed based only in antral biospies Method of DNA extraction and analysis should be
described in full details Uni-multivriated analysis is more appropriated to define the specific
weight of each risk factor Results Patients demographics should be given intially  Thereafter
changes in cagA motif should follow and risk factors determining changes And then changes in
gastric pathology and their relation to changes in cagA motif should follow Finally changes in
patients symptoms and their relation to cagA motif changes should follow
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 3 Date: 14 Sep 2024
Reviewer's report:
This study from Iran aimed to identify changes in the cagA EPIYA motif patterns during a
10-year follow-up and to explore how lifestyle factors such as smoking, alcohol consumption,
gender, and age influence these changes. In about half of the 100 patients included in the study,
notable changes occurred in the motif pattern of H. pylori cagA during the 10-year period. The
study also found a significant association between changes in pathology outcomes with gender
(P= 0.01) and smoking (P= 0.00).
Major Comments
1. Although approved by a local ethics committee in Iran, I find quite unethical the fact that the
patients had not received specific H. pylori treatment upon its initial detection or during the 10-
year period. H. pylori is a class I carcinogen according to the World Health Organization, and not
offering an H. pylori eradication regimen to patients with dyspeptic health issues for 10 whole
years, for the sake of an observational basic research study without any obvious clinical benefit,
seems rather inappropriate and a malpractice, at least to the eyes of a clinician. Were participants
explicitly informed that they would not receive treatment for H. pylori for the entire 10-year
period? Were the risks of non-treatment, such as the progression to gastric ulcers or cancer, fully
explained to them? I am truly concerned about whether the study’s benefits justify the risks.
2.  Antibiotic use over the 10-year period could have inadvertently affected the H. pylori
bacteria (e.g., partial eradication or selection of resistant strains), thus impacting the results.
Not controlling for this variable could undermine the reliability of the study's findings. The
manuscript does not appear to address how these confounding effects were mitigated.
3. The authors should explain how consistent the biopsy procedures were between the initial and
follow-up samples, as this could affect the comparability of the results.
4. The reliance on PCR-based methods alone, without culturing or histopathological
confirmation of H. pylori, might miss cases of bacterial overgrowth, co-infections, or other
pathologies. Also, it is not clear how the changes that occurred in the motif pattern of H. pylori
cagA affected the mucosa histopathology, based on the Correa's cascade of gastric cancer.
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 4 Date: 01 Oct 2024
Reviewer's report:
-
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 4 Date: 02 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Changes in pathological findings should be differentiated from clinical picture Gastric
pathology related to change of demographics should be reported Last sentence should be called
conclusions The one before is obscure and should be defined If the result is non significant it
should be omitted from the abstract Methods Authors should define what they did with marginal
cases; those they had one positive biopsy and negative RUT  or positive RUT and negative
histology Do they vrepeated endoscopy and biopsy taking or there are no data since those
patients were excluded from the study Actually RUT could be positive if non H.pylori bacteria
producing urease are present Do authors reuse biopsy forcepts? Authors should determine
what was the role of PCR in H. pylori diagnosis Was it  an exclusion criterion if not enough
DNA was available to perform PCR Results:First paragraph of results needs some linguistic
adaptation Changes in patient symptomatology and in gastric pathology should be presented
in different sections To evaluated the effect of demographic and clinical characteristics to
clinical picture and gastric pathology or any other secondary target should be evaluated using
logistic regression analysis ( univariated and multivariated) instead of mixed chi-square/t-test
and logistic regression Pictures use would be helpful
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 4 Date: 03 Oct 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The adjustments are approved for publication.
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 5 Date: 09 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
I think that changes requested have been applied Thus after introducing results of multivariated
analysis in the abstract it could be accepted for publication
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 6 Date: 15 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Because cagA changes cagA changes should be also included in logistic regression
analysis  and the same should be done in the results if the sample of the study permits such a
change Relevant pictures if available could be included
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 7 Date: 21 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
At the moment the main problem of the document is the need for linguistic guidance I suggest
that authors should better defined worsening in gastric pathology related to CagA motif changes
by providing more data in the relevant results section  I also suggest that authors might
introduced some pictures
Review for 10.1186/s12876-024-03516-0 (2024)

Title: Long-Term Assessment of Helicobacter pylori cagA EPIYA Motif Changes and
Pathology Outcomes in Gastric Biopsies of Dyspeptic Patients: 10-year Follow-up
Version: 8 Date: 28 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
I think the study is ready of publication Thus I congratulate the authors
Review for 10.1186/s12876-024-03558-4 (2024)

Title:  The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control
study
Version: 2 Date: 30 Jun 2024
Reviewer's report:
1. Authors stated they included “first-degree relatives” of the patients in the abstract and
discussion, while we also saw “family members” in the study community. Authors stated the
they selected first-degree relatives for the control group as they “had the same environmental
conditions as the sick subjects”, and it made the spouse a reasonable choice for the control group.
Then why they select first-degree relatives as the control?
2. The sample size was small, and authors should state how they calculated the sample size.
Authors should state the definition of “respond to treatment methods”, and also explain why
they separated UC patients into “responded to treatment” and “did not respond to treatment”.
3. Participants with high CRP in the UC groups and control groups were 17 (70.83)/18 (78.26)
and 14 (58.33)/12 (52.17), authors should explain why the controls had high CRP, what were
the concomitant diseases of these participants.
4. More work is needed for a logical discussion.
Review for 10.1186/s12876-024-03558-4 (2024)

Title:  The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control
study
Version: 2 Date: 01 Jul 2024
Reviewer's report:
I have reviewed the manuscript.
The study addresses a very current topic, but the number of patients is not sufficient to draw
a conclusion. When assessing the disease and evaluating vitamin D levels, the duration of the
disease is very important. In addition, other important factors such as parathyroid hormone
levels, calcium levels, and whether the patient has chronic kidney disease have not been
included. The relevance of whether the patient had COVID-19, as indicated in the table, is
unclear to the topic. The concept of a treatment-refractory patient is not well defined. It is unclear
whether it refers to a patient unresponsive to first-line treatments or a patient unresponsive to
steroids. The reason why first-degree relatives of the patients were chosen as the control group
should be explained.
In its current form, the manuscript does not seem suitable for publication in the journal.
Review for 10.1186/s12876-024-03558-4 (2024)

Title:  The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control
study
Version: 4 Date: 01 Aug 2024
Reviewer's report:
Authors did not answer the former comment "Authors should state the definition of 'respond to
treatment methods' ".
They now stated the treatment methods with sentences “three stages of treatment were
performed. Patients who responded to each of these three stages were selected as treated
individuals (group 1), but those who did not respond to all three stages were selected as
treatment-resistant individuals (group 3). The treatment steps of the patients were as follows:
The first stage of treatment was 5-aminosalicylic acid (5-ASA) treatment. The second stage of
treatment was treatment with glucocorticoids and azathioprine. The third stage of treatment was
a biological treatment that includes anti-TNF-# which includes Infliximab and Adalimumab.
Inclusion of the study: In the treated group (group 1), all those who responded to each of the
three treatment steps were included in the study, and the treatment-resistant group (group 3), all
those who did not respond to all three treatment steps were included in the study.”
However, they still did not state how to define a response. Is it a mucosal healing?
“This study was a case-control type and 4 groups of people were included in this study. Given
an 80% power and the type I error of 0.05, and considering an effect size of 0.80 according to
the study of Lamb et al (18), the calculated sample size using GPower was equal to 23 persons
for each group.”
Authors now wrote the above sentences in the Material and Methods. I suggested go for a
statistician to make certain that the number of patients is sufficient to make a conclusion, as
authors cited a reference published 22 years ago (2002) and many things might have changed.
More work is needed for an understandable presentation, and I failed to understand many
sentences, for example:
1. The results of Vitamin D; Mean (Std. dev.) analysis with demographic variables and other
blood factors show that in the group 1 UC patients and group 2, people whose BMI is <18.5 have
the highest Vitamin D; Mean (Std. dev.), which include 27 (12.11) and 28 (8.19) respectively.
2. However, the point of interest in this study is that in patients who are resistant to treatment
and their first-degree relatives who had a BMI less than 18, the level of vitamin D was lower
than that of treated people and even their relatives.
3.In a retrospective study, the average level of vitamin D in people with ulcerative colitis was
17.1±9.7 and in healthy people was 20.4±7.0 (24), although the average level of vitamin D in
this study was lower than our study, in this study, similar to our study, there is a significant
relationship with ulcerative colitis.
…
Review for 10.1186/s12876-024-03558-4 (2024)

Title:  The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control
study
Version: 4 Date: 02 Aug 2024
Reviewer's report:
Dear Editor
Thanks for sending me the manuscript entitled ‘ Investigating the role of vitamin D in treated
and refractory ulcerative colitis patients: a case-control study’ for revision
- The relation or impact of vit D and IBS was extensively studied but yet still important
- AS regard to abstract in result sector need to be claried or reformulated’ in the group of
ulcerative colitis patients was 45.88 (18.51) and in the resistant group was 41.30 (13.01).
Vitamin D; mean (std. dev.) in the group of ulcerative colitis patients was 24.96 (9.66) ng/mg and
in the resistant group was 27.70 (12.28) ng/mg, showing that there is no significant difference
in terms of serum vitamin D.’
What is meant by ulcerative colitis group (you mean the responders??)
- The study group was 24 , then in results was subdivided according to severity into 4 subgroups ;
one of them was 2 patients , how can we apply statistical analysis in such low number,
- Still it is important topic but need answers about patient numbers and sample size
thanks
Review for 10.1186/s12876-024-03549-5 (2024)

Title: Long-Term Outcomes of S-1 and Oxaliplatin Neoadjuvant Chemotherapy with Total
Mesorectal Excision and Lateral Lymph Node Dissection for Rectal Cancer
Version: 3 Date: 13 Jun 2024
Reviewer's report:
"Phase II study. 52 patients. Aim to evaluate the long-term outcomes of S-1 and oxaliplatin with
total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiation
for rectal cancer.
"
Thanks to the authors for submitting their work to BMC gastroenterology. I would consider it
for publication after major revisions.
1. Despite of general adequate grammar, it is advisible to make revisions of the manuscript'
structure and get it revised by a native english speaker in order to assure appropriate meaning
of sentences as well as readability.
2. Introduction: I suggest to use standard nomenclature. Total mesorectal excision instead of
total mesenteric excision. Central lymph node dissection is implied in the definition of TME.
3. Methods seccion: 58 patients included in the first work, 52 in the latter. Are the included
patients from a single institution?
4. Results:
1.This section is improvable by adding appropriate statistical information such as HR, CI and
p values. E.g. Rephrase the sentence "the risk factors for local recurrence were mucinous
carcinoma not adenocarcinoma" stating it objectively.
2.What does mean "ineligibility for R0 resection"?
3. In table 2 "resection margin" is the same as Circumferencial Resection Margin? or is it what
you describe as "inegibility for R0"?
4.Tables/figures:
*I suggest to use a more specific or descriptive tittle for tables. E.g table 3, prosgnostic factors
for what? OVERALL SURVIVAL?.
*Also, use a footnote to the table/figures describing abbreviations.
*In the figures, include the statistical method used. Is it a Kapplan-Meier as stated in methods?
if so, the number at risk is missing.