JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-024-03451-0 (2024)

Title: 5-Hydroxyindoleacetic Acid as a biomarker for revealing perforation in acute appendicitis
Version: 1 Date: 07 Sep 2024
Reviewer's report:
1. IT WAS STATED THAT POWER ANALYSIS WAS PERFORMED FOR THE STUDY
AND 150 PATIENTS WERE DETERMINED.
ACCORDING TO PATHOLOGY RESULTS, IT WAS STATED THAT ALL 150 PATIENTS
WERE DIAGNOSISED AS PERFORATED OR NONPERFORATED. IN SURGICAL
PRACTICE, IT IS NOT POSSIBLE FOR ALL 50 PATIENTS TO BE DIAGNOSED WITH
APPENDICITIS.
SOME PATIENTS ARE DIAGNOSED AS NEGATIVE APPENDICITIS. IN ACTUALLY,
THE NUMBER INCLUDED IN THE STUDY SHOULD BE MORE SO THAT THE
NUMBER OF PATIENTS DIAGNOSED WITH APPENDICITIS CAN BE REACHED.
IN THIS CASE, OUR REAL SAMPLE NUMBER SHOULD BE MORE OR THOSE WHO
WERE NOT PATHOLOGICALLY DIAGNOSISED WITH APPENDICITIS IN THE NON
PERFORATED PATIENT GROUP SHOULD BE SPECIFIED.
2. IN THE DISCUSSION SECTION, SIMILAR STUDIES WERE LISTED ONE BY ONE
AND THEIR RESULTS WERE EXPRESSED.
SCIENTIFIC EVALUATION OR COMPARISON WAS KEPT AWAY.
THE AUTHORS HAVE EXPRESSED THAT THEY HAVE SIMILAR RESULTS WITH
THEIR OWN STUDIES, BUT ALMOST ALL OF THE EXAMPLES THEY GAVE
CONSISTED OF AUTHORS WHO HAVE REACHED THE OPPOSITE CONCLUSIONS.
3. THE AUTHORS CLAIM THAT IF PERFORATION IS DETECTED, THIS SITUATION
WILL SHAPE THE INCISION CHOICE. I REGRET TO STATE THAT THIS CAN ONLY
BE A CLAIM. AS LONG AS FACTORS SUCH AS THE DEGREE OF PERFORATION,
PRESENCE OF PHLEGMON, AND EDEMA STATUS IN THE CECUMA ARE NOT
KNOWN, THE INCISION CHOICE MAY REMAIN ONLY AN INTENTION. 5HIAA
LEVELS DO NOT CONTRIBUTE TO ANY OF THESE ISSUES.
4. 5 HIAA IS A SUBJECT THAT HAS BEEN STUDIED IN THE LITERATURE, AND
MANY STUDIES WITH A LARGER NUMBER OF SAMPLES HAVE RESULTS THAT
ARE OPPOSITE TO WHAT THE AUTHORS CLAIMED. A CURRENT META-ANALYSIS
DATED 2023 (Arredondo Montero J, Bueso Asfura OE, Pérez Riveros BP, López Burgos
E, Rico Jiménez M. Diagnostic performance of urinary 5-Hydroxyindoleacetic Acid in acute
appendicitis: a systematic review and diagnostic test accuracy meta-analysis. Int J Colorectal
Dis. 2023 Nov 20;38(1):269. doi: 10.1007/s00384-023-04556-w.) stated that 5 HIAA was not
beneficial in complicated or noncomplicated acute appendicitis. The authors' results will be
meaningful only if they can provide scientific interpretation or evidence to the studies and such
meta-analyses that claim the opposite. Otherwise, they will be left with fewer cases compared to
the data in the literature. No opinion was put forward against other publications in the discussion
section.
Review for 10.1186/s12876-024-03451-0 (2024)

Title: 5-Hydroxyindoleacetic Acid as a biomarker for revealing perforation in acute appendicitis
Version: 2 Date: 16 Sep 2024
Reviewer's report:
The article was reevaluated in light of the comments made to the criticisms. When the revised
version of the article was evaluated in light of the responses given, the study was deemed
appropriate.
Review for 10.1186/s12876-024-03451-0 (2024)

Title: 5-Hydroxyindoleacetic Acid as a biomarker for revealing perforation in acute appendicitis
Version: 2 Date: 21 Sep 2024
Reviewer:  Sadettin Er
Reviewer's report:
The article is quite important in terms of markers for predicting perforated appendicitis. It is
valuable as it provides direction to clinics with limited resources. I think it would be beneficial
to publish it.
Review for 10.1186/s12876-024-03447-w (2024)

Title: Integrin #5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis
and immunotherapy efficacy in gastric cancer
Version: 0 Date: 17 Jul 2024
Reviewer:  Anwar Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below:
-Have you had the opportunity to conduct scratch assays ?
- Additionally, have you performed exosome isolation and characterization to study the
characteristics of exosomes?
-In your baseline characteristics, have you included information on HER2, ITG#v, metastasis,
Who, and Lauren classifications?
-Furthermore, have you had the chance to perform a liquid biopsy to analyze circulating tumor
cells or cell-free DNA in the blood?
Review for 10.1186/s12876-024-03447-w (2024)

Title: Integrin #5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis
and immunotherapy efficacy in gastric cancer
Version: 0 Date: 28 Jul 2024
Reviewer's report:
Dear Colleague,
Thank you for conducting this research. I would like to discuss a few points with you.
Firstly, the manuscript contains numerous grammatical and flow-related errors. Please review
and correct these to ensure clarity and coherence.
In the introduction, you state: "It is often the case that the bulk of GC diagnoses occur in the late
stages of disease during their initial visit, inevitably leading to a 5-year survival rate of under
10% and a lack of effective biomarkers for diagnosis and targeted therapeutic interventions."
Therefore, you test ITGB5 between two groups: one with 375 cases of GC and 32 controls.
However, to validate this properly with a control group, you need to ensure an overpowered
control group. This is typically in a 1:2 or even 1:4 ratio to confirm that the degree of occurrence
and control is corrected. Here, you use only 32 controls, which significantly diminishes the
power of detecting ITGB5 or any biomarker. This methodology appears flawed, and a larger
control group is necessary.
The introduction outlines the difficulty of early detection, so how do you plan to implement this
practically? Considering that patients usually present at late stages, what is your aim? To detect
tumors earlier? Please elaborate on the practical implications of your findings.
Regarding the statistical analysis, while your methods are correct, they are rather basic. You
compare groups and determine the presence or absence of significance. However, GC patients
and controls differ substantially in disease stages, necessitating matching to ensure each GC
patient has an identical control without GC.
From an epidemiological standpoint, it is crucial to ensure no confounding factors in both groups
could skew the results. This analysis appears to be missing.
You use Cox regression analysis, but with only 32 controls, you can officially correct for
only three variables. You do not have unlimited access to all variables, as the smallest group
determines your capacity for correction, not the 375 cases. For instance, you cite age as a value,
but has this been corrected for as a confounder, given that GC is typically diagnosed at a late
stage? The same question applies to the disease stage. age was not significant, but how was this
corrected, and does this still hold in stratification?
The results section is seven pages long but fails to clearly present key points. Given the
aforementioned limitations, many of the results raise doubts. How do you apply correlations
with other immune checkpoint-related mRNA in daily practice? This and comparisons to other
literature and implications for future practice are missing from the discussion.
In summary, the study presents numerous uncertainties and lacks clarity on how to proceed and
the contribution of regression analyses. As it stands, the manuscript is not ready for publication.
Best regards,
Review for 10.1186/s12876-024-03447-w (2024)

Title: Integrin #5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis
and immunotherapy efficacy in gastric cancer
Version: 1 Date: 28 Aug 2024
Reviewer:  Anwar Abouelnasr
Reviewer's report:
changes are done, accepted for publication
Review for 10.1186/s12876-024-03447-w (2024)

Title: Integrin #5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis
and immunotherapy efficacy in gastric cancer
Version: 1 Date: 29 Aug 2024
Reviewer's report:
Dear Colleague,
Thank you for addressing all the questions.
While we may have differing views on some points, I appreciate your input.
However, it is important to include in the limitations section that the limited sample size
prevented you from adequately controlling for all potential confounding factors. Although Cox
regression can account for some variables, the small patient cohort made it challenging to do
so effectively was my point.
Review for 10.1186/s12876-024-03447-w (2024)

Title: Integrin #5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis
and immunotherapy efficacy in gastric cancer
Version: 2 Date: 06 Sep 2024
Reviewer:  Anwar Abouelnasr
Reviewer's report:
Changes are done, accepted for publication
Review for 10.1186/s12876-024-03450-1 (2024)

Title: Bacterial and Clinical Metabolic Signatures and Their Interactions in Obese Patients Post-
Bariatric Surgery
Version: 5 Date: 29 Jul 2024
Reviewer's report:
Thank you for your valuable article and it is my pleasure to review the manuscript of BMC
Gastroenterology " Changes and Effects of Intestinal Microbiota after Laparoscopic Sleeve
Gastrectomy".
In this paper, the authors compared the composition of the intestinal microbiota in obese patients
before and after laparoscopic sleeve gastrectomy (LSG) through 16S rDNA analysis of the stool
samples. In the results, LSG increased the richness and diversity of the intestinal microbiota in
obese patients after surgery.
This paper gives us the important information, however it has some weaknesses. Thus, it needs
to be revised in some respects. I would provide the following comments and queries.
Major Comments
1. In general, weight loss after LSG does not reach a plateau at 6 months after surgery. Why
did you compare the intestinal microbiota before and 6 months after surgery? If you compared
before and 1 year after surgery, you might get a clearer result.
2. In the Methods section, please provide more details about the 16S rDNA Sequencing and
Analysis, or cite a reference.
3. Please explain what indices related to #-diversity analysis are shown in Fig. 2A. Did #-
diversity decrease after LSG?
4. this study conducted Spearman correlation coefficient analysis between post-bariatric surgery
patients' gut microbiota and clinical indicators, as shown in Fig. 4. Is not there any benefit to
conducting Spearman correlation coefficient analysis between pre-bariatric surgery patients' gut
microbiota and clinical indicators?
5. Bypass procedures like the RYGB or DS could be expected to alter the microbiota especially
in the small intestine. Why should we expect to have such changes after a LSG?
6. At the phylum and class level, there are statistically significant changes in the microbial
communities, although some of these appear to be very small changes. Do the authors believe
this will make a clinically significant change?
Review for 10.1186/s12876-024-03450-1 (2024)

Title: Bacterial and Clinical Metabolic Signatures and Their Interactions in Obese Patients Post-
Bariatric Surgery
Version: 5 Date: 02 Sep 2024
Reviewer's report:
The authors evaluate the changes and effects of intestinal microbiota after laparoscopic sleeve
gastrectomy (LSG). They found that LSG reduced patients' BMI and altered the composition
of the intestinal microbiota in obese patients in China. However, many studies also showed
significant gut microbiota change after bariatric surgery already.
Comment
1. You can have three groups for comparison, obesity before LSG, after LSG, and normal BMI
control.
2. Do you have the data of stool metabolites before and after LSG, it is also very important in
these bariatric patients. They are strong associated with or related to gut microbiota.
3. Do you have the data of gut hormones like GLP-1, PYY before and after LSG, they may have
changed after surgery.
4. Diet can modify the body weight, gut microbiota, do you record the diet pattern, food amount
before and after LSG ?
5. Are you sure it is 16srDNA rather than 16srRNA in DNA analysis of the stool samples ?
6. Do you have the legends for figure 2-D.
7. In the discussion, you described that there are significant population differences in species-
level diversity, the analysis of V3,V4 16srRNA in your study cannot discrete the gut microbiota
into species-level.
8. In the legend of figure 4, “black indicates positive correlation, and red indicates negative
correlation. The size of the circles represents the magnitude of the correlation, with larger circles
indicating higher correlation values.” What are higher correlation values, for example r=0.7 or
0.8, please quantify them.
Review for 10.1186/s12876-024-03450-1 (2024)

Title: Bacterial and Clinical Metabolic Signatures and Their Interactions in Obese Patients Post-
Bariatric Surgery
Version: 6 Date: 29 Sep 2024
Reviewer's report:
Thank you for your valuable article and it is my pleasure to review the manuscript of BMC
Gastroenterology "Bacterial and Clinical Metabolic Signatures and Their Interactions in Obese
Patients Post-Bariatric Surgery".
The manuscript has been revised well about the content to be discussed. This paper will be
valuable to readers.
Review for 10.1186/s12876-024-03454-x (2024)

Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 1 Date: 29 Aug 2024
Reviewer's report:
The study included both major depression and depression, but in the methods (section 2.2), no
definition on major depression. please describe how depression and major depression in both
NHANES and MR analysis. Please also clarify whether constipation is chronic or transient in
the study. Depression/major depression are chronic from clinical perspective. Please clarify this
as well.
The flow chart for the NHANES analysis is helpful, it would be very helpful to provide flowchart
for the MR analysis given its complexity. For example, how many patients were included from
what database and what were the SNPs included (and excluded) in the analysis, what was the
main analysis, and what were the sensitivity analyses, etc.
The NHANES analysis showed that the association between depression and constipation is valid
among those without vigorous activities. Did the MR analysis take this into consideration? It’s
not mentioned at all.
Results (section 3.2) described a significant nonlinear relationship between depression scores
and risk of constipation. Does this mean both very low and high depression scores are associated
with constipation? Please include some interpretation on this.
The results from MR analysis of depression and constipation are very different from than those
from NHANES analysis: ORs were drastically higher, is this plausible? In contrast, the ORs on
major depression and depression from MR analysis are lower than NHANES analysis. Some
explain would be appreciated.
In the discussion, the authors said that antidepressant medication may alleviate constipation
to explain the weak association in MR analysis. However, some antidepressants can also
increase the risk of constipation. Also, the study excluded those with diarrhea (as described in
the NHANES analysis, not clear in MR analysis), then likely only those who well tolerated
antidepressants (who had no diarrhea) were included in the study, thus the representativeness
of the study population is limited.
“In conclusion, we combined cross-sectional studies from NHANES with bidirectional two-
sample MR analysis”. But it seems that these two analyses were separate: different study
population, and results were not compared or linked somewhat.
Given the above, the conclusion on the causal inference is seeming too assertive. Discussions on
the limitations of the MR analysis in this study would be helpful, for example, potential violation
of assumptions for the methods used (IVW method, MR-Egger, etc).
Review for 10.1186/s12876-024-03454-x (2024)

Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 2 Date: 05 Sep 2024
Reviewer's report:
Thank you for diligently addressing the revisions as requested#I think your manuscript now
meets the standards for acceptance by the journal.
Review for 10.1186/s12876-024-03454-x (2024)

Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 2 Date: 12 Sep 2024
Reviewer's report:
• Many claimed revisions in the response can’t be found in the manuscript at the stated lines.
Just to name one example: comment 3 from reviewer 1, the response said that they have added
a brief overview of the methods and explained why the threshold is chosen in line 160-162, and
line 143-144, but they can’t be found in the manuscript. Please check throughout the manuscript
and fix.
• Regarding the response to comment 1 from reviewer 2 (me), could the authors provide a brief
description of the data they used for MR analysis as they did for NHANES data? Is the data
from clinical EMR? Or something else? How is (major) depression measured in these datasets?
• Can the authors briefly explain how was physical activity as a confounding factor accounted
for in the SNP selection stage? This info should be added to the manuscript as well.
• In the response, the authors tried to explain why the effect sizes (ORs) differ drastically between
MR analysis and NHANES analysis. Is the first reason claiming that GWAS result is less robust?
Also these info should be also added to the discussion section in the manuscript to improve the
quality.
• Regarding the complex relationship between depression and bowl dysfunction (constipation
and diarrhea), could the authors consider including diarrhea in the analysis, so that outcome is
categorical instead of binary? The reference category is patients without either constipation or
diarrhea, and the analysis could show whether depression increased the risk of either one of
them, or both of them. This could also potentially avoid the selection bias.
• The authors indicate that potential bias from MR methodology is included at line 295-297,
again they are not found in the manuscript there.
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 3 Date: 25 Aug 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract: turning point of the nomogram should be given Also indication for steroid use should
be included Methods Indication for steroids should be defined ( what the size of big lesions?)
Also glucocorticosteroid receptor expressions in the pathology report is rather vague Patient
demographics should be given Authors should explain why they selected 3/4 of lumen diameter
for their model and then 7/8 for steroid ineffectiveness Results of the univariated analysis should
be also provided before presenting results of multivariate analysis Percentages should be given
apart from crude numbers  Risk factors for stenosis should be calculated separately Discussion
should be adapted accordingly
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 3 Date: 29 Aug 2024
Reviewer:  Yasuaki Nagami
Reviewer's report:
This is a single-center retrospective study that evaluated stenosis prediction, The score for
each risk factor, Risk factors of ineffective oral steroid prophylaxis , and glucocorticoid
receptor expressions . Author concluded In the high-risk group with a circumferential mucosal
defect involving 7/8 or more, oral steroid treatment tends to be ineffective. The higher
glucocorticoid receptor # may indicate potential glucocorticoid resistance, possibly participating
in the ineffective treatment..
Nice study, but I have some comments.
Major Comments
1. I think this study is complicated because multiple outcomes in different group of patients. I
recommend you reduce outcomes in patients with oral steroid.
2. I think you should evaluate prediction model in patients with or without perophylactic
treatment. Or you should include and analyze steroid therapy in multivariate analysis. From table
1, steroid therapy wasn’t analyzed by multivariate analysis, was it?
3. How did you select factors to analyze multivariate analysis. Please describe it.
4. From Table 3, maximum score point seems to be 7 (location 2, circum 4, diameter 1). But,
you showed 9 point in bottom of Table 3. Please show how to use it.
5.  Please show how you take specimens for immunohistochemistry. If you used ESD specimen,
biopsy specimen before treatment is enough for examining those? Because we want to know
that information before treatment. Please add it to limitations.
6.
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 5 Date: 11 Sep 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Methods authors should provide reference for resistant stenosis definition Parameters collected
should be defined Results It should be mentioned that univariate analysis was performed and
results are presented in table 1 Formula of the nomogram should be provided
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 5 Date: 25 Sep 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The changes have been made and accepted for publication.
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 6 Date: 30 Sep 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Changes are done , accepted for publication
Review for 10.1186/s12876-024-03448-9 (2024)

Title: Prediction of post-ESD Esophageal Stricture by a Nomogram and Risk Factor analysis
of Ineffective Oral Steroids Prophylaxis
Version: 6 Date: 30 Sep 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Suggested changes have been made Thus I propose that the document can be accepted
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 2 Date: 03 Jul 2024
Reviewer:  Ramona S. S. B. Boulhosa
Reviewer's report:
This is a clinically relevant paper, with a clear objective, a well-described methodology, and
results that contribute to the understanding of the best nutritional indicators in the prediction
of clinical outcomes.  When reading the manuscript, I did not observe a discussion about the
fragility of the BMI and % of weight loss variables in this population, since 79% of those
evaluated had ascites. It is important to emphasize that, as this is a retrospective study, the
assessment of the degree of ascites is highly subjective and may be a bias in the estimation of
dry weight.
Finally, there is no information on how many of these patients had a previous diagnosis of
cirrhosis and its respective causes. The presence of a chronic liver alteration associated to HCC
may explain malnutrition and early mortality in these patients.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 2 Date: 16 Jul 2024
Reviewer's report:
The authors have addressed a contemporary topic with high relevance for patients and the health
care system. So far, there are only limited studies about GLIM malnutrition diagnosis in HCC
patients and the descriptive data of the manuscript are of interest for clinicians and researchers.
The GLIM consensus criteria are the currently available diagnostic criteria for the assessment
of malnutrition combining phenotypic and etiologic aspects. One central phenotypic criterion
is the reduction of muscle mass. One main aim of the present study was to assess the clinical
application of the GLIM criteria with and without muscle mass in HCC patients.
The reason for excluding one central criterion from malnutrition diagnosis is not clear to
me. Especially in patients suffering from severe liver disease, overhydration is a common
complication,  masking the other phenotypic criteria (reduced BMI, weight loss). Therefore,
the muscle mass which was assessed by the gold standard CT in this study, needs to be of
particularly high importance. As a consequence of excluding the criterion reduced muscle mass,
numerous malnourished patients were not recognized by this approach leading to altered results
of the comparison of malnourished and non-malnourished patients. This seems logical and is
not helpful in terms of validation of the GLIM criteria or improving the diagnostic procedure
in HCC patients. In conclusion, despite the interesting topic, the orientation and argumentation
of the paper is not convincing.
Moreover, the manuscript and the attached files are in part poorly prepared. The cited literature
is not always reflecting what was stated in the text. A response letter for Frontiers in Nutrition
was attached which I am suprised about.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 08 Aug 2024
Reviewer's report:
Dear Author, please find some suggestions for your manuscript below:
Is it possible to provide more data on sarcopenia and its relationship with tumor recurrence,
progression-free survival, tumor response, and drug toxicity to develop a comprehensive
understanding of sarcopenia's impact on clinical outcomes in HCC patients, not limited to overall
mortality?
While the SGA is simple to use, several research studies have challenged its precision in cirrhotic
patients. The RFH-SGA was created due to the restrictions of the SGA in cirrhotic patients. Can
a comparison be made between the GLIM Criteria and RFH-SGA criteria?
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 09 Aug 2024
Reviewer's report:
Thanks to the authors for their response and clarifying the aim of the present study.
According to the authors, the main aim was to assess the clinical application of the GLIM criteria
with or without CT-determined reduced muscle mass in patients with HCC. I totally agree that
skeletal muscle mass has an indispensable role as a GLIM criterion and the importance of CT-
derived data for malnutrition diagnosis is immense, as this method represents the gold standard
and provides reliable results (also in patients with ascites). However, it makes little sense to
assess malnutrition without taking muscle mass into account. In my opinion, another method
(such as BIA or muscle performance which is also discussed) would have been an appropriate
control if the importance of CT scans was to be the focus. The results achieved in the present
manuscript are therefore kind of self-fulfilling.
I acknowledge that an additional paragraph on ascites was made. However, my concerns were
not taken into consideration in the revised version of the manuscript, not even as a limitation.
For this reason, unfortunately, I cannot see any improvement of the revised manuscript.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 10 Aug 2024
Reviewer's report:
The authors have addressed a very interesting topic for the prevalence of malnutrition using the
GLIM criteria in HCC and the importance of the assessment of muscle mass in these patients.
The study is well-designed, and the results and the discussion sections are well-written. I have
only one comment to address:
I understand that GLIM criteria using the phenotypic criterion of reduced muscle mass should be
applied instead of using them without information about the reduced muscle mass. However, in
the clinical practice what do you recommend when CTs are not available? Please add a comment
for what do you recommend to apply in the clinical practice for the assessment of muscle mass
in the discussion section.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 11 Aug 2024
Reviewer's report:
The authors present an interesting, though not novel, manuscript. They showed that patients
with HCC and concomitant malnutrion have a higher mortality rate than HCC patients without
malnutrition. The article is well written, however I have a few suggestions.
1. A control group of cirrhotic patients with no HCC should be added, otherwise this should be
added to limitations section
2. The fact that HCC per se leads to malnutriotion due to inflammation should be added in
causes of malnutrition due to HCC (ref: doi: 10.1002/hep.30036; doi: 10.3390/ijms23169430;
doi: 10.1038/s41590-018-0044-z)
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 12 Aug 2024
Reviewer:  Ana Brito-Costa
Reviewer's report:
This is a very interesting and clinically relevant paper that contributes to the understanding of
the best nutritional indicators in the prediction of clinical outcomes.
The manuscript has been carefully reviewed, but should still undergo a more detailed review
of the english writing (eg. influence of "nutriture" on liver disease: p.3, 1st paragraph; the
"counting" data were measured by a chi-square test: p. 5, 3rd paragraph).
Additionally, I would like some clarification about the exclusion criteria applied (some of them
do not make sense under the objective of assessing the prevalence of undernutrition using the
GLIM criteria).
The methodology states that the GLIM criteria were only applied to individuals classified with
nutritional risk by the NRS-2002; however, data subsequently indicates that all individuals were
classified using the GLIM criteria. Can you clarify?
Why  youdid not assess the severity of malnutrition?
Finnally, regarding the low intake criteria, did the authors compare macronutrient intake with
the recommended intake or just used the energy intake? It would be interesting to see if there is
any relation between the deficient intake of any specific macronutrient.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 3 Date: 12 Aug 2024
Reviewer's report:
This is a nice study evaluating the added value of incorporating muscle mass by CT scan in the
GLIM criteria in patients with HCC. The study successfully points out that reduced muscle mass
is an integral part of malnutrition assessment and should be used when possible.
Major remarks:
1. Contrary to the manuscript's statements, another study assessed GLIM criteria using CT
scan evaluation of L3-SMI  in patients with HCC. (Tan, S., Jiang, J., Qiu, L., Liang,
Y., Meng, J., Tan, N., & Xiang, B. (2024). Prevalence of Malnutrition in Patients with
Hepatocellular Carcinoma: A Comparative Study of GLIM Criteria, NRS2002, and PG-SGA,
and Identification of Independent Risk Factors. Nutrition and Cancer, 76(4), 335–344. https://
doi.org/10.1080/01635581.2024.2314317).
Please revise the statement and proceed to compare the results of these studies.
2. A practical comment regarding incorporating such measurements in clinical practice would
be most helpful. Can L3-SMI be evaluated retroactively in a CT scan used for the diagnosis
of HCC? Are there any special steps to be taken? Can this methodology be easily incorporated
into clinical practice?
Minor remarks:
Page 2, Introduction Line 7, can(c)er
Page 4, Lines 1 and 2: patients who were long-term bedridden, exclude diagnosed with
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 4 Date: 29 Aug 2024
Reviewer's report:
Li et al. presented a study looking at the association between reduced muscle mass in Global
Leadership Initiative on Malnutrition in the mortality risk of patients with HCC. They found
that the GLIM was independently associated with increased risk of mortality. Further, including
CT assessed muscle mass as an extra indicator increased the sensitivity of GLIM in identifying
patients with malnutrition, and it also showed independent association with HCC mortality in
hospital.
The results presented with thorough details in a scientific manner. However my major concerns
are
1. HCC is one of the major outcomes of chronic liver diseases. Major factors associated with
the mortality risk of patients with HCC are factors mainly associated with chronic liver disease
such as portal hypertension and liver decompensation, but not so much are factors with HCC per
se (tumour invasion, etc). This is drastically different from other types of major organ cancers.
However, the authors didn’t discuss factors associated with liver decompensation, nor tumour
invasion including HCC staging at baseline, tumour number and sizes, any tumour metastases, or
any HCC treatment. Although undoubtedly nutritional status is associated with health outcomes
in patients with HCC, a conclusion drawn by excluding adjustments of these major factors would
not be anyway near accurate.
2. For patients with chronic liver disease, HCC and other liver decompensation outcomes will
most likely occur around the same time. In this study cohort, did all the patients have only HCC
but not other liver decompensation? As authors listed in Table 1, short-term outcomes included
HE, ascites, etc. However, my argument is that these outcomes especially ascites, had occurred
before or around the same time as HCC, therefore it couldn’t be labelled as an outcome. As
discussed above, none of these are outcomes of HCC. They are outcomes of chronic liver disease.
This would be a logical, not necessarily a clinical issue, in analysing and interpreting the survival
data. Patients with malnutrition had worse liver outcomes than patients without malnutrition,
which has been published widely, and has little to do with the HCC status.
3. What is the exact purpose of excluding muscle mass as a diagnosis criterion in GLIM in the
first part of data analysis? The GLIM criteria have clearly listed reduced muscle mass as one of
the phenotypic criteria published in 2019. If accessibility is the reason, authors need to discuss
this further.
4. Figure 3 is a bit confusing, did the authors try to predict the total mortality risk by nutritional
status alone? What is the clinical significance of this analysis?
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 4 Date: 01 Sep 2024
Reviewer's report:
Thanks to the authors for their response and clarifying the aim of the present study. The authors
have addressed a very interesting topic for the prevalence of malnutrition using the GLIM criteria
in HCC and the importance of the assessment of muscle mass in these patients. The study is
well-designed, and the results and the discussion sections are well-written.
Review for 10.1186/s12876-024-03438-x (2024)

Title: Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition
criteria in nutritional diagnosis of hepatocellular carcinoma
Version: 4 Date: 01 Sep 2024
Reviewer's report:
The authors have substantially improved their manuscript. I think that despite a signifacnt
number of limitations the article can be accepted for publication
Review for 10.1186/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 4 Date: 01 Aug 2024
Reviewer's report:
Dear Editor, thank you so much for inviting me to revise this manuscript about malignant hilar
obstructions.
This study addresses a current topic.
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 treatment scenario for cholangiocarcinomas and the topic of malignant
jaundice should be further discussed and some recent papers added within the introduction
( PMID: 32606139; PMID: 33571059 ; PMID: 38791914 ; PMID: 36533070 ), 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. In fact, the sample size is very small, and the authors should further
discuss this issue.
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/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 4 Date: 04 Aug 2024
Reviewer:  Naminatsu Takahara
Reviewer's report:
Thank you very much for giving me the opportunity to review the paper titled "Biliary
Drainage in Palliative and Curative Intent European Patients with Hilar Cholangiocarcinoma
and Malignant Hilar Obstruction: A Retrospective Single Center Analysis." While I appreciate
the effort and significance of better biliary drainage results in patients with curative disease, I
believe the authors need to provide more information on the methods used to improve the paper.
1. The authors stated that the decision on therapy concepts (curative versus palliative) was
discussed in the hospital’s interdisciplinary tumor board. However, the criteria for determining
curative versus palliative disease in the tumor board remain unclear.
2. The authors used four alternative definitions of clinical success as bilirubin decrease in this
study. However, the major aim of biliary drainage should be not only to reduce jaundice but
also to provide opportunities for antitumor therapy, avoid biliary events such as cholangitis, and
maintain quality of life (QoL). Shouldn't the appropriateness of the treatment be evaluated using
outcomes that reflect these goals?
3. Please describe the treatment content and strategies after biliary drainage for both curative
and palliative diseases. If the treatment strategies differ between the two groups after biliary
drainage, it is likely that the observation periods between the two groups will differ. Therefore,
please clarify the observation periods for both groups.
4. Differences in patient backgrounds and observation periods can impact treatment outcomes
(i.e., the longer the observation period, the higher the likelihood of increased reintervention rates
due to stent occlusion, whereas the shorter the observation period, the higher the likelihood of
underestimating the frequency of complications). Comparing treatment outcomes between these
two groups with different patient backgrounds requires careful interpretation. This should be
clearly stated as a major limitation of this study.
5. It is desirable to evaluate adverse events by dividing them into early (within 2 weeks) and
late (after 2 weeks) occurrences.
6. Please confirm the timing of the evaluation of clinical success.
7. In Table 2, the number of procedures is noted, but over what period were these procedures
performed? Are reinterventions for stent occlusion also counted? The results may vary
depending on the observation period.
Review for 10.1186/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 6 Date: 01 Sep 2024
Reviewer:  Naminatsu Takahara
Reviewer's report:
The authors correctly responded to the comments from editor and reviewers.
Review for 10.1186/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 6 Date: 02 Sep 2024
Reviewer's report:
The manuscript by Drews and colleagues addresses a topic that has a strong impact on the actual
clinical practice of patients with hilar cholangiocarcinoma.
However, the authors should clarify the following aspects:
- The study design consists in a direct comparison of patients in two different disease settings
(curative and palliative) that significantly differ in terms of clinical outcomes and survival;
therefore, this could represent a significant bias in the analysis and should be better addressed.
- The authors should point out another limitation of the study: the choice of the same TSB target
for the two different categories of patients. In clinical practice, the target of bilirubin after biliary
drainage may differ between patients eligible for surgery with curative intent and those eligible
only for palliative chemotherapy.
- In the “Materials and Methods” section, the authors state: “Given the European
recommendation and the accumulation of data in favor of metal stents in palliative pCCA, we
started using bilateral uncovered metal stents in palliative patients with poor functional status
and/or poor prognosis; these patients were not included in the analysis.”
Why did the authors not include these patients considering that European guidelines and actual
practice in Western countries recommend this approach?
- In the results section, the authors should include
• the type of chemotherapy treatment in the palliative group
• the rate of biliary events such as cholangitis and stent occlusion
Review for 10.1186/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 7 Date: 16 Sep 2024
Reviewer:  Naminatsu Takahara
Reviewer's report:
Acceptance
Review for 10.1186/s12876-024-03429-y (2024)

Title: Biliary Drainage in Palliative and Curative Intent European Patients with Hilar
Cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis
Version: 7 Date: 23 Sep 2024
Reviewer's report:
This is a retrospective review of the outcomes in biliary drainage in hilar CCA patients, it is an
important study that sheds light on the risk factors. The endpoints chosen by authors is unique
but practically useful and can be translated into clinical practice.  The limitations are expected
ones from a retrospective study.
Overall, a useful study for medical oncologists, surgeons, and gastroenterologists.
Review for 10.1186/s12876-024-03446-x (2024)

Title: The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a
systematic review and meta-analysis
Version: 1 Date: 22 Jun 2024
Reviewer's report:
The authors submitted the protocol to PROSPERO retrospectively, which may impact the
transparency and reliability of the study.
The reporting of the current study is suboptimal and requires substantial revision to meet the
standards for publication in a scientific journal.
The study appears to be outdated, as the last search strategy was performed in October 2022.
Review for 10.1186/s12876-024-03446-x (2024)

Title: The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a
systematic review and meta-analysis
Version: 1 Date: 04 Jul 2024
Reviewer's report:
In the present systematic review with meta-analysis, Authors found that at diagnosis only a minor
percentage of celiac disease (CD) patients were underweight, while high BMI was associated
with CD diagnostic delay. Main comments:
1) A linguistic revision is necessary.
2) Literature search was updated to almost 2 years ago (October 2022).
3) I do not understand why, if > 800000 healthy controls were found, Authors analyzed only raw
percentages (with which method? inverse variance? This was not stated) in celiac patients instead
of making a comparison with controls. This would have given more interesting results whether
prevalence of obesity/underweight were more or less common in CD. Of note, an analysis of
this type was reported in figure 7, but no details about the type of meta-analysis was reported
in the Methods section.
4) The last three lines in Discussion paragraph of the Abstract seem to give a contradictory
message regarding the link between age and BMI.
Review for 10.1186/s12876-024-03446-x (2024)

Title: The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a
systematic review and meta-analysis
Version: 1 Date: 11 Jul 2024
Reviewer:  Ana Luísa Falcomer
Reviewer's report:
This highly relevant article will be disruptive in celiac disease research and valuable to health
professionals involved in CD screening and diagnostics. It effectively challenges the outdated
notion that celiacs are usually underweight when diagnosed.
I truly enjoyed reading it. Congratulations on the excellent work!
In the interest of helping to improve the manuscript quality, I have attached a file with my
feedback and suggestions.
Thank you for the opportunity to assist you in bringing this important study to the scientific
community.
Review for 10.1186/s12876-024-03446-x (2024)

Title: The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a
systematic review and meta-analysis
Version: 2 Date: 13 Aug 2024
Reviewer's report:
The authors submitted the protocol to PROSPERO retrospectively, which may impact the
transparency and reliability of the study.
The reporting of the current study is suboptimal and requires substantial revision to meet the
standards for publication in a scientific journal.
Review for 10.1186/s12876-024-03446-x (2024)

Title: The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a
systematic review and meta-analysis
Version: 2 Date: 13 Aug 2024
Reviewer's report:
Significant improvement to the manuscript. Only comment is that the study by Barone et
al. in Nutr Rev. actually does look at BMI prior to diagnosis (and also after diagnosis). So the
authors do need to address how their study is different, or at least mention this other article.