JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-023-03106-6 (2024)

Title: Gastroparesis might not be Uncommon in Patients with Diabetes Mellitus in a Real-World
Clinical Setting: a cohort study
Version: 0 Date: 12 Nov 2023
Reviewer's report:
The authors investigated the frequency of diabetic gastroparesis and associated risk factors in
a real-world clinical setting. They showed that 70.8% of DM patients had abnormal GET, as
well as retinopathy and peripheral neuropathy were associated with a higher frequency of DGP.
Numerous reports have already been made on DGP, and this article lacks novelty. In addition,
the relationship with microvascular complications such as diabetic neuropathy and abnormal
GET is well known. On the other hand, I agree with the methodology of using GET evaluation in
solid meals using Tc-99m-phytate scintigraphy. There are several problems to resolve as below.
1. It is a major limitation that the authors did not investigate the relationship between
gastrointestinal symptoms and GET.
2. The authors should clarify the content of diabetic medicines because these cannot be excluded
as confounding factors. (e.g. GLP-1 analog is known to inhibit GET)
3. The authors should show the relationship between delayed GET, rapid GET and post-prandial
glucose levels.
4. Does abnormal GET cause high blood glucose levels, or does high blood glucose levels cause
abnormal GET? Or both?
5. As stated by the authors, it is known that DGP is more common among females and there is a
gender difference in GET. But in this study, the influence of gender difference on GET was not
evaluated. It is desirable to perform a separate analysis by gender or multivariate analysis.
6. In Abstract, is word "64.9 years" a mistake for "65.0 years" and "60.0 years" for "60.2 years"?
7. In Abstract, is word "15.5 vs 6.0%" a mistake for "6.0 vs 15.5%"?
8. In "Clinical characteristics according to GET in DM patients" section on page 9, is word
"P=0.044" a mistake for "P=0.030"?
9. In Figure 1, the graph bars for rapid and delayed GETs are reversed for DM patients.
Review for 10.1186/s12876-023-03106-6 (2024)

Title: Gastroparesis might not be Uncommon in Patients with Diabetes Mellitus in a Real-World
Clinical Setting: a cohort study
Version: 3 Date: 06 Dec 2023
Reviewer:  Zaigham Salim Dar
Reviewer's report:
Research and review have been conducted adequately
Review for 10.1186/s12876-023-03106-6 (2024)

Title: Gastroparesis might not be Uncommon in Patients with Diabetes Mellitus in a Real-World
Clinical Setting: a cohort study
Version: 3 Date: 11 Dec 2023
Reviewer's report:
The authors have made point-by-point corrections to the peer review comments. But some issues
remain unresolved.
1. The authors conducted additional linear regression analyzes on the association between gastric
emptying time and diabetes mellitus with associated covariate (Table 3 and Table 4). They
should describe these analyzes in the Statistical analyses section.
2. Regarding Table 3, for delayed GET and nephropathy, the authors described as “# -2.922,
p=0.041”. But the description in the main text is “# -2.924, p=0.000”. Please correct either
description. Also, even though the CIs in the nephropathy are over 0 (-5.72,0.13 for delayed
GET, and -3.13,0.74 for Rapid GET), there are significant difference. Please check if the CIs
are correct.
3. Regarding Table 3, there is no description about hypoglycemia. The authors should add
descriptions of the results in the table.
Review for 10.1186/s12876-023-03106-6 (2024)

Title: Gastroparesis might not be Uncommon in Patients with Diabetes Mellitus in a Real-World
Clinical Setting: a cohort study
Version: 5 Date: 23 Dec 2023
Reviewer's report:
The authors have made appropriate corrections in accordance with the reviewers' point-by-point
comments. There will be no need for any further changes, and it is considered this manuscript
is acceptable.
Review for 10.1186/s12876-024-03126-w (2024)

Title: Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis
Version: 4 Date: 18 May 2023
Reviewer's report:
Well-written manuscript with an in-depth review of the literature. Some comments regarding
style -
-Abstract: Write out the full form of MAP in the result section of the abstract
-Add % of patients who has severe acute pancreatitis with reference in the introduction
-Write out the full form of Ca2+ levels, NF-#B, IL-6, TNF, TLR4 etc. when used first time
Review for 10.1186/s12876-024-03126-w (2024)

Title: Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis
Version: 4 Date: 10 Jul 2023
Reviewer's report:
The article deals with a very important topic, since severe acute pancreatitis is a life-threatening
condition, the timely discovery and prediction of which can affect the therapy.  Based on my
opininion here are my recommendations:
- In the introduction, not only the obesity but also the metabolic syndrome and the increased
risk for SAP (PMID: 31620021) and increased occurence of AP (PMID: 33407178) should be
mentioned.
-In the methods section, the search key is not complete, the supplementary table3 is not cited.
Was language restriction or other filters used during the search?
- Was the same definition of AP, SAP and MAP used in the articles?
-Although the conclusion is that resistin could be a biomarker for the detection of SAP, I miss the
mention of the use of score systems suitable for assessing SAP in the introduction and discussion.
PMID: 31507427, PMID: 31947993, PMID: 35653504
-How accessible is resistin as a marker? Could it be widely used? On its own or perhaps
integrated into score together with other parameters?
Based on these points, it is a major revision, the article needs to be revised.
Review for 10.1186/s12876-024-03126-w (2024)

Title: Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis
Version: 8 Date: 21 Dec 2023
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?
Yes - the author's interpretation is reasonable
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: This is the review of the MS evaluating value of adipokines for
predictive assessment of the severity of acute pancreatitis using meta-analysis. Resistin, but
not leptin or visfatin, was found as promising as biomarker and, possibly, a therapeutic target.
Authors did great job on revision, MS is now ready for publishing.
ADDITIONAL REQUESTS/SUGGESTIONS:
Great job on revision. now MS is ready for publishing
Review for 10.1186/s12876-023-03112-8 (2024)

Title: Long term persistence and risk factors for anorectal symptoms following low anterior
resection for rectal cancer
Version: 2 Date: 01 Aug 2023
Reviewer:  Wilhelm Graf
Reviewer's report:
Thanks for the opportunity to review the manuskript describing the funktionalitet outcome after
sprinter presenning surgery for rectal cancer. My comments are listen below.
1. It is virtuella impossible to draw firm conclusions based on diagnostical and therapeutic
measures since these measures are based on a percieved clinical need in view of the individual
patient.
2. A more rewarding strategy would be a prospective protocol demanding all participants to
undergo examinations and treatment.
3. The failure to detect efficacy of BF treatment is most likely due to that treatment was given
to those with worse symptom.
4. The distance from the anal verket is important for functional outcome. The authors only
describe coloanal vs colorectal which is to crude.
5. Likewise, anastomotic dehiscence should be exactly defined.
6. The authors found that time to stora closure correlated to function. However there maybe
confounding by anastomotic complications causing a delar to closure.
7. The time for manometry varied considerably which is a clear limitation. The lack of
standradization makes results inconclusive.
8. Thee abstract contain a recommendation for sacral neuromudulation which is not bsed on the
study results.
Review for 10.1186/s12876-023-03112-8 (2024)

Title: Long term persistence and risk factors for anorectal symptoms following low anterior
resection for rectal cancer
Version: 2 Date: 01 Oct 2023
Reviewer's report:
Well written paper evaluating anorectal function (AF) in patients undergoing Low Anterior
Resection (LAR) with defunctioning stoma (DS) for cancer.
An important subject that help understanding the impact of rectal resection and constructing an
anastomosis of anal canal with the sigmoid colon at the level of pelvic floor.  It is a well-known
phenomenon and generally called Low Anterior Resection Syndrome (LARS).
I comment each part separately to give as distinct feedback as possible.
Title
I suggest that the title indicate somehow that the paper even evaluates the impact of DS on AF.
Abstract
I suggest the use of LAR instead of sphincter preserving surgery due to the last mentioned term
dos not strictly indicate, total mesorectal excision (TME) while LAR does, an important detail
that partially explains the poor AF outcomes after surgery.
The term severe LARS is unnecessary because the LARS Score already has categorized LARS
to 3 categories no-LARS, minor-LARS and major-LARS. Terms that should be used throughout
the paper instead of severe or mild LARS.
Introduction
Some spelling correction The R is missing in Rectal second line.
Some repetitive segments in first paragraph “decrease of the need for abdominoperineal
resection with colostomy”
Suggest additional references when indicated LARS and quality of life, second paragraph.
It should be risk for recurrence and not chance of recurrence when mentioning the role of
adjuvant chemotherapy and risk for major-LARS.
Design
The paper is a population based prospective design in my opinion due to the intervention in this
study is done prospectively (the questionnaires) even if it has a retrospective part.
Method
It should stay if the LARS score is validated to Hebrew language in Israel with references.
Results
The reason for late stoma reversal should be mentioned and discussed as a possible explanation
for poor AF outcome. If the late reversal is due to low priority or if it is due to adjuvant therapy.
The late reversal and adjuvant therapy may both have an impact on the poor outcome as you
have mentioned in the paper yourself and should be taken to consideration.
I am emphasizing that the term Major LARS (Score #30) should be used and not severe LARS.
Is it right to say that there is no differences between male and female regarding major-LARS at
all in your study? If not how is that in content to previous puplications?
Gender – male; n (%) 37 (67%) 17 (68%) NS
Discussion
The reason for late stoma reversal should be mentioned and discussed as a possible explanation
for poor AF outcome. If the late reversal is due to low priority or if it is due to adjuvant therapy.
The late reversal and adjuvant therapy may both have an impact on the poor outcome as you
have mentioned in the paper yourself and should be taken to consideration
In summery I recommend this paper to be published with this minor considerations
Review for 10.1186/s12876-023-03065-y (2024)

Title: RNA N6-methyladenosine demethylase FTO targets MOXD1 promoting the malignant
phenotype of gastric cancer
Version: 2 Date: 12 Sep 2023
Reviewer's report:
In the current study the author explored the expression and clinical effect of FTO in gastric
cancer and further investigated the possible mechanisms. There are several points need to be
considered carefully
1. The expression status, survival analysis and function of FTO have been well studied in GC
in previous study (PMID 35064107) thus the significance of the current study is poor.
2. Many grammatical mistakes are found in the manuscript in the background section “Aims of
this study to analyze the function of differentially expressed gene of FTO depleted GC cells,
and further explore the targeted genes of FTO downstream modification in GC.”
3. All the expression data are present with public data set or qPCR. The protein should be
examined.
4. In Figure 7C the gating of the FACS should be identical in NC and MOXD1 knock down
gourp
4. The author explored the function of FTO and MOXD1 separately but the author intended to
show “FTO targets MOXD1 promoting the malignant phenotype of gastric cancer”. Since the
function of FTO in GC has been studied in GC, to increase the novelty of the current study the
author should investigate the function and mechanisms of MOXD1 instead of FTO
”
Review for 10.1186/s12876-023-03065-y (2024)

Title: RNA N6-methyladenosine demethylase FTO targets MOXD1 promoting the malignant
phenotype of gastric cancer
Version: 2 Date: 07 Oct 2023
Reviewer:  Yuan-Feng Zeng
Reviewer's report:
Review comments
The manuscript is well, concisely and coherently presented. The title reflects the main subject
of the manuscript and the abstract summarizes the work described in the manuscript. Through
multidimensional bioinformatics analysis and functional validation experiments, the authors
proved that the key demethylase of m6A FTO promoted the malignant phenotype of GC cells
via regulating the oncogene related pathways. In addition, FTO improved the degradation of
MOXD1 mRNA via m6A modification. The elevated expression of MOXD1 was linked with
the promotion of malignant phenotype in GC cells, as well as unfavorable prognoses in GC.
The results are reliable and the conclusion is credible. So, my final review comment is to
recommend that the paper be accepted.
However, I  think there are two clerical errors in the manuscript in lines 173 and 234,
which explain the relationship between increased MOXD1 expression and prognosis in gastric
cancer patients. They contradict the relevant content explained in lines 253-254 and the results
presented in Figure 2. Please carefully check and verify by the authors.
Review for 10.1186/s12876-023-03095-6 (2024)

Title: Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients
with metabolic syndrome
Version: 0 Date: 03 Nov 2023
Reviewer's report:
Hello
This article is very well-designed and well-written, and it uses precise tools to examine fatty
liver steatosis and fibrosis (fibroscan 502 ecosense), and the article is worth printing, but there
are points for correction that will be provided to the author in each section.
Review for 10.1186/s12876-023-03095-6 (2024)

Title: Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients
with metabolic syndrome
Version: 0 Date: 05 Nov 2023
Reviewer's report:
The manuscript entitled as ‘Association of insulin resistance indicators with hepatic steatosis and
fibrosis in patients with metabolic syndrome’ by Kuo, et al. used the data of 876 participants with
MetS from the National Health and Nutrition Examination Survey 2017-2018, and investigate
the association of four insulin resistance (IR) indicators with hepatic steatosis and fibrosis, and
compare the diagnostic value of these indicators in identifying hepatic steatosis and fibrosis.
They showed that HOMA-IR, TyG-WHtR, and METS-IR is associated with the risk of hepatic
steatosis and fibrosis among the U.S. adult population with MetS. Additionally, TyG-WHtR is
a good predictive factor for hepatic steatosis and hepatic fibrosis. However, there are several
concerns for publication.
1. While HOMA-IR, TyG, TyG-WHtR, and METS-IR are each considered indicators of insulin
resistance, I am curious as to why only TyG did not emerge as a significant factor in predicting
hepatic fibrosis. It is important for the authors to provide an explanation for this finding.
2. The authors conducted a subgroup analysis by age and gender. However, it would be even
more intriguing to investigate whether there are variations in the relationship with insulin
resistance based on the extent of hepatic steatosis and fibrosis. Additional analysis is warranted.
3. The definitions of certain diseases and conditions, such as MetS, drinking status, hepatitis, and
CVD, lack clarity in the manuscript. It is necessary for the authors to provide clear definitions
for these terms within the scope of their study.
4. It would be of interest to have information on the diagnostic accuracy, Positive Predictive
Value (PPV), Negative Predictive Value (NPV), Sensitivity, and Specificity of each insulin
resistance indicator. We recommend that the results be included in the presentation.
5. While this study was conducted using data from the United States, a study utilizing Chinese
data would carry more significance if it were reported from China.
Review for 10.1186/s12876-023-03095-6 (2024)

Title: Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients
with metabolic syndrome
Version: 1 Date: 12 Dec 2023
Reviewer's report:
The revisions made in response to the reviewers' comments have strengthened the paper and
aligned it more effectively with the aims and scope of publication.
Review for 10.1186/s12876-023-03117-3 (2024)

Title: Clinical study on the necessity and feasibility of routine MRCP in patients with
cholecystolithiasis before LC
Version: 2 Date: 12 Nov 2023
Reviewer's report:
Thank you for the opportunity of reviewing this paper, very interesting study on a much debated
topic.
However, some issues need to be clarified.
In the introduction section:
- the sentence  at lines 56-57 should be referenced (studies confirming the MRCP as main method
for diagnosis of CBDS);
- among the factors of suspicion of CBD stones you should add the history of pancreatitis,
besides the dilated common bile duct on abdominal ultrasonography examination and a regular
appearance of the main extra-hepatic bile duct with abnormal levels of liver function tests;
- the interrogative sentences at lines  68-69 should be removed to my opinion, reporting  only
the main objective of the study;
In the method section I don't understand why patients with elevated direct bilirubin in non-
MRCP group did not perform MRCP pre-operatively? This is an important limitation of this
retrospective study;
The true problem to be solved is the management of patients with low-risk for CBD stones
(5-10%). We would do useless MRCPs in the remaining 90-95% of the population and with
higher costs.
Moreover, another factor should be considered, the spontaneous passage of small CBD stones.
In a recent study solitary and CBDSs sized < 6 mm may pass into duodenum before ERCP
(Unnecessary endoscopic retrograde cholangiopancreatography associated with the spontaneous
passage of common bile duct stones into the duodenum: a multicenter retrospective study. Surg
Endosc. 2023). This issue should be clarified in the discussion.
Regarding the sentence at line 270-273,  in 2019 Pesce A et al. analyzed the effectiveness
of NIRF-C in the detection of cystic duct-common hepatic duct anatomy intra-operatively in
comparison with pre-operative MRCP with high diagnostic accuracy values (Effectiveness of
near-infrared fluorescent cholangiography in the identification of cystic duct-common hepatic
duct anatomy in comparison to magnetic resonance cholangio-pancreatography: a preliminary
study. Surg Endosc. 2020). The multimodal imaging combining pre-operative MRCP to exclude
the presence of bile duct stones in high-risk patients and intra-operative navigation with
fluorescence
for better definition of biliary anatomy would be beneficial to replace IOC, which is time
consuming and burdened by morbidity (the authors should also consider this paper  titled Critical
View of Safety During Laparoscopic Cholecystectomy: From the Surgeon's Eye to Fluorescent
Vision. Surg Innov. 2018).
However, the cost-analysii is limited in China, so it needs multicenter studies from different
countries confirming the feasibility of pre-operative MRCP before all cholecystectomies in
terms of healthcare costs.
The manuscript needs careful editing by someone with expertise in technical English editing.
Review for 10.1186/s12876-023-03117-3 (2024)

Title: Clinical study on the necessity and feasibility of routine MRCP in patients with
cholecystolithiasis before LC
Version: 2 Date: 25 Nov 2023
Reviewer:  Akira Umemura
Reviewer's report:
Usefulness of preoperative MRCP have been already proven. I do not have any new findings
from this article.
Review for 10.1186/s12876-023-03117-3 (2024)

Title: Clinical study on the necessity and feasibility of routine MRCP in patients with
cholecystolithiasis before LC
Version: 4 Date: 16 Dec 2023
Reviewer's report:
When reviewing the authors’ responses and the latest version of the manuscript, I evaluated the
accuracy and validity of the manuscript. The authors addressed my comments and substantially
improved the quality of the paper.
Concerning the question point 7  the response is not completely satisfactory. I think that your
comment should be added in the discussion  with the suggested references, so I suggest the
authors to write that in few lines in order to underline the importance that multimodal imaging
technology such as intraoperative fluorescent cholangiography combined with pre-op MRCP
examination are  very useful for better definition of biliary anatomy in such contexts. It is very
important for readers to better understand this issue, by improving the quality of your paper.
Review for 10.1186/s12876-024-03119-9 (2024)

Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 3 Date: 12 Nov 2023
Reviewer's report:
1. General comment
This paper by Zhao et al. entitled "The P2Y1 receptor in the colonic myentric layer of rats
and its correlation with opioid-induced constipation" is an interesting study on opioid-induced
constipation was associated with alteration in the function and expression levels of P2Y1
receptors in rat colonic myenteric layers.
In general, this is a well-written paper. These findings will be interesting for gastrointestinal and
general practitioners as well as researchers in those field. But before this paper will be reached
to the criteria, the authors should be answered the mentioned below.
2. Major comments
(1) Opioid-induced constipation means narcotic analgesic user suffer from constipation. The
Loperamide treatment is the antidiarrheal agents, but not narcotic analgesia.  Therefore,
the author described that Loperamide-induced constipation mean as the opioid-induced
constipation. It is difficult to understand your concept.
(2) Figure 2, 3, and Table1, did you study the effect of naloxone, opioid a #-receptor antagonist,
on loperamide-induced constipation in rat.
(3) The author should mention about the role of serotonin in opioid-induced constipation as well
as P2Y receptors in discussion.
3. Minor comments
(1) Page numbers should be put on your paper.  It was difficult for us to read and find out
keywords.
(2) The author should describe more about the selectivity or affinity of MRS2500, a P2Y1
receptor antagonist, as compared with MRS 2179 in “materials and methods”.
(3) Page 7 Line 7 from the bottom, “ZYQ” should be removed on your paper.
(4) Pape 10 Figure3, MOR in rat colonic colonic muscle layer.  Should be removed the second
“colonic”.
(5) Page 12 Line 12, OIC is is characterized by ~. Should be removed the second “is”.
Review for 10.1186/s12876-024-03119-9 (2024)

Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 5 Date: 29 Dec 2023
Reviewer's report:
The authors have responded appropriately to all my questions on the revision of the article.
Therefore, this article is acceptable.
Review for 10.1186/s12876-024-03119-9 (2024)

Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 5 Date: 30 Dec 2023
Reviewer's report:
You answered my questions so that your paper should be open to the publich.
In addition, I look forward to further analysis regarding OIC-induced constipation from the
viewpoint of serotonin.
Review for 10.1186/s12876-023-03115-5 (2024)

Title: Esophageal cancer: a twenty-four-year experience at a tertiary care center with an
evaluation of the prognostic significance of the Neutrophil-Lymphocyte ratio
Version: 3 Date: 20 Oct 2023
Reviewer's report:
The authors state the two aims of this study; describing the clinic-pathologcal features of
esophageal cancer in Lebanon, and to report if NLR is prognotic factor.
I have three major concerns
1: The authors describe the clinic-pathologcal features of more than 110 patients from a single
center, about 2/3rd of them were from the home country, and the others from enighbouring
country. Hoiwever, authors also discuss the incidience and age-standardized incidence and
compare them with data published regionally and internationally. When almost, 1/3rd of the
patients are not from Lebanon, how do authors justify the comaprison.
2: Prognotic value of NLR was a major aim of theis study. The authors do not describe how
neutriophil and lymphcyte numbers were obtained or calculated. If they used an automated
counter, how were the results validated. What instrument was used to report the differential
coutns, and if there were quality checks. In the bastract, authors mention that NLR was not
predictive either of the disease type or other parameters, but do mention of AUC. AUC is not
described elsewhere. how was it calculated. The auhtors may want to discuss the limitation of
the study, the way neutrophil and lymphocyte numbers were obtained
3:Although the primary aim was to report NLR and clinic-patholiigal features, the authors
discuss incidence of disease. There is no mention of how the incidence figures were obtained
There are some other points. LMS and NHL, are not esophageal cancers, and should not be
included in analysis.
The authors may wish to have the manuscript proof-read by either by a native speaker or
professional medical editing services
Review for 10.1186/s12876-023-03115-5 (2024)

Title: Esophageal cancer: a twenty-four-year experience at a tertiary care center with an
evaluation of the prognostic significance of the Neutrophil-Lymphocyte ratio
Version: 3 Date: 30 Oct 2023
Reviewer:  Shunji Endo
Reviewer's report:
There are few papers on esophageal cancer from the Middle East, so I think this is a valuable
epidemiological study.
I think that the following sentence is an important result; “After adjusting for age, gender, TNM
staging and grading, cox regression analysis showed that an increased NLR was a significant
predictor of mortality, with an adjusted hazard ratio of 1.095 (p=0.011).”, but I would like to
see a figure or table that visually appeals to this.
Review for 10.1186/s12876-023-03115-5 (2024)

Title: Esophageal cancer: a twenty-four-year experience at a tertiary care center with an
evaluation of the prognostic significance of the Neutrophil-Lymphocyte ratio
Version: 4 Date: 17 Dec 2023
Reviewer:  Shunji Endo
Reviewer's report:
I have no further comment.
Review for 10.1186/s12876-023-03089-4 (2024)

Title: Efficacy and safety of tacrolimus in older adults with ulcerative colitis: A retrospective
study
Version: 3 Date: 13 Oct 2023
Reviewer's report:
It is a very pertinent and well conducted study. The elderly patient group include a very small
number of patients, this negatively effects the results. Important to highlight the efficacy and
safety of a oral cheaper alternative to biological therapy in moderate to severe ulcerative colitis.
The study can be accepted in its current form.
Review for 10.1186/s12876-023-03089-4 (2024)

Title: Efficacy and safety of tacrolimus in older adults with ulcerative colitis: A retrospective
study
Version: 3 Date: 28 Oct 2023
Reviewer's report:
I am very pleased to have had the opportunity to review this manuscript. This study investigated
the usefulness and safety of tacrolimus in elderly patients with ulcerative colitis. The study of
tacrolimus in elderly patients is a novel and interesting study. However, this manuscript may
require the following revisions.
Major
Introduction
#The fact that tacrolimus was shown to be useful in treating ulcerative colitis in a large-scale
clinical trial should also be mentioned in the introduction section.
Materials and Methods
#May score, which is a colonoscopy score, is confused with Mayo score, which includes partial
Mayo and Mayo endoscopic subscore. The endoscopic score should be indicated as the Mayo
endoscopic subscore.
#In TAC treatment of ulcerative colitis, a high trough is generally achieved, and then a transition
is made to a low trough. In what range was the target trough value of the TAC set?
#Was the target trough achieved in all registered patients?
Results
#It would be good to have a visual representation of the registered patients and those that were
subsequently followed. Can you show me the study flow chart?
#The remission rates for one month of TAC initiation are as stated, but what about the response
rate?
#Please indicate the p-value for the rate of change in GFR for each period in young and older
patients in Fig. 1.
-Hyperkalemia is often a clinical problem in the treatment of ulcerative colitis with tacrolimus.
Did this study not consider hyperkalemia as an adverse event?
Discussion
#In this study, TAC administration was continued based on the ECCO guidelines. Japanese
regulations indicate that the treatment period is 3 months, but are there any other Japanese papers
that consider its administration for more than 3 months?
Minor
- Not all abbreviations were explained in each table. Please add them to the table.
- The first letter of each item in adverse effects in Table 2 should be capitalized.
- The phrase "time to reach TAC trough" should be changed to "time to reach target TAC trough".
Review for 10.1186/s12876-023-03089-4 (2024)

Title: Efficacy and safety of tacrolimus in older adults with ulcerative colitis: A retrospective
study
Version: 3 Date: 02 Nov 2023
Reviewer:  Saurabh Dawra
Reviewer's report:
The authors have chosen a novel and niche aspect of UC management However, a few queries
require arise
1 kindly describe in brief , your institutes management protocol for management of UC
especially steroid refractory UC
2 How do you decide to give Tacrolimus instead of Cyclosporine/ TNF Alpha inhibitors
3 When do you initiate Tacrolimus in patients? What is your dosing schedule: Intravenous or oral
4 How many patients underwent colectomy after tacrolimus therapy vs non tacrolimus group
5 Does Tacrolimus therapy increase ris of infections in the two groups is there any data available
on this aspect
6 Why have you chosen to describe ASA allergy Is it related to response to Tacrolimus therapy
in any way
7 More patients in younger group have biological exposure as compared to elder group? Has
this affected the disease response in any way kindly elaborate
Review for 10.1186/s12876-023-03089-4 (2024)

Title: Efficacy and safety of tacrolimus in older adults with ulcerative colitis: A retrospective
study
Version: 8 Date: 10 Dec 2023
Reviewer:  Saurabh Dawra
Reviewer's report:
The queries have been  answered. Suggest editing the introduction and review by a native English
language expert.
Review for 10.1186/s12876-023-03109-3 (2024)

Title: The Effectiveness of Continuity of Care in Patients with Inflammatory Bowel Disease:
A Systematic Review
Version: 1 Date: 05 Nov 2023
Reviewer's report:
Please insert newer reference for epidemiology (reference is from 2017).
Rephrase the 2nd sentence in introduction.
In the paper decide and use researchers or investigators (i would prefer investigators).
Who were investigators - do they have any experience in ibd?
Review for 10.1186/s12876-023-03109-3 (2024)

Title: The Effectiveness of Continuity of Care in Patients with Inflammatory Bowel Disease:
A Systematic Review
Version: 5 Date: 25 Dec 2023
Reviewer's report:
Dear authors,
Thank you very much for the revised manuscript. I have checked your  highlighted parts  the
manuscript and response to reviewer. I believe you have made a good revision.
Review for 10.1186/s12876-023-03088-5 (2024)

Title: Growth development of children and adolescents with inflammatory bowel disease in the
period 2000-2014 based on data of the Saxon Pediatric IBD Registry: A population-based study
Version: 0 Date: 30 Sep 2023
Reviewer:  Matthew Carroll
Reviewer's report:
Thank you for the opportunity to review this manuscript which has analyzed growth trends at
diagnosis in a regional German cohort of pediatric patients with IBD. These data confirm our
existing understanding of the impact of IBD upon growth but do not provide new insights or
understanding.  The authors state that studying the growth patterns of children with IBD leads to
the creation and improvement of an effective and efficient care structure for IBD health services
but fail to explain how. What link does growth data have to improved care, in particular, cross
sectional growth data at diagnosis rather than longitudinal data that may reflect the superiority
of certain therapies over others?
There are several grammatical issues that need to be addressed.
line 39-40: "...was for children both sex negative" - this does not make sense. Please revise. I
believe  you mean that there were no observed differences between genders?
Line 43-44: same as above
Line 42: please indicate which version of the child growth curve was used (KIGGS)
line 61: please explain what 'S3' is
line 68-70:  this should indicate that these changes are with respect to the Saxony cohort as per
the reference listed
line 77-82: very long sentence with awkward syntax. Suggest revising
Line 113-115: confusing structure. The 421 patients with anthropometric data consisted of 250
males and 171 females. Sentence needs to be reworded.
line 26: delete "There were"
line 147 and figure 2: MC and CU need to be defined - only exist as abbreviations on x-axis.
Same for figure 4. Furthermore, they are not included in the subsequent table of abbreviations.
line 210: suggest substituting "apparent" or "present" for "obviously"
line 221: remove comma after "that"
line 222: remove the 'with' preceding 'underweight'.
line 223: remove comma after 'with'; insert 'an' before 'increased', change 'at' to 'by'
line 223: change 'has' to 'have'
line 231: remove comma after 'proposed'; parental should not be capitalized
line 235-237: How has the creation of your database led to the creation and improvement of an
effective and efficient care structure for IBD health services. What have you done, what have
you changed about your care and delivery structure/methods?
line 248: delete 'but it could not be larger'
Review for 10.1186/s12876-023-03088-5 (2024)

Title: Growth development of children and adolescents with inflammatory bowel disease in the
period 2000-2014 based on data of the Saxon Pediatric IBD Registry: A population-based study
Version: 0 Date: 08 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (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 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 - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Thank you for allowing me to review this interesting and well written
study.
1. Are the authors able to assess the impact of different treatment (biologics vs non-biologics),
disease duration, disease severity and extent on the weight and height of these children?
2. Are the authors able to demonstrate if early onset IBD is associated with more abnormal height
and weight compared to disease that happens late?
REQUESTED REVISIONS:
Please see the comments above.
ADDITIONAL REQUESTS/SUGGESTIONS:
Please see above
Review for 10.1186/s12876-023-03088-5 (2024)

Title: Growth development of children and adolescents with inflammatory bowel disease in the
period 2000-2014 based on data of the Saxon Pediatric IBD Registry: A population-based study
Version: 1 Date: 06 Dec 2023
Reviewer:  Matthew Carroll
Reviewer's report:
Thank you for addressing the review comments
Grammatical changes suggested:
end of  line 99 "die" should be "the"
line 124 "have" should be "had"
Review for 10.1186/s12876-023-03088-5 (2024)

Title: Growth development of children and adolescents with inflammatory bowel disease in the
period 2000-2014 based on data of the Saxon Pediatric IBD Registry: A population-based study
Version: 1 Date: 07 Dec 2023
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?
Yes - the author's interpretation is reasonable
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: The authors have answered the queries satisfactorily. I have no
further edits.
Review for 10.1186/s12876-023-03108-4 (2024)

Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 1 Date: 12 Oct 2023
Reviewer's report:
As it is generally acknowledged, UDCA remains the first-line therapy for the disease, but
alternative therapies, such as obeticholic acid, have recently emerged, albeit restricted to patients
with either intolerance or poor response to UDCA.  The authors performed an observational
study, analyzing records from a large urban health system with regards to medications.
Accordingly, they managed to quantify candidacy and usage rates of pharmacotherapy in
patients with an established diagnosis of PBC. Of interest, they noted an almost universal
compliance to guidelines and UDCA prescription.
However, I would like to comment on the following:
1) Background: It is well-known that use of UDCA has improved the natural history of the
disease, but ref 3-6 reflect mainly historical data. It should be noted that the disease nowadays
is detected in earlier stages and epidemiology has slightly changed.
2) Table 1 should be improved in terms of appearance/design, i.e the total sample size would
better be presented in the first raw (n=495) instead of a separate one. In addition, regarding
ethnicity, it is not clear why patients of Hispanic origin are considered  as a distinct population,
since in that case the total number of patients would be 505. It would be also interesting if
demographic parameters other than ethnicity could be included, such as age, disease duration
and presence of cirrhosis (clinical or in imaging).
3) Results: calculation of percentages is not always straightforward (it is unclear if the calculation
corresponds to the total sample size or not). It would also be helpful to explain what the
difference between barrier and lack of offering OCA is. Also, there is a significant amount
of patients who were not offered OCA for indeterminate reasons or received indeterminate
medication and therefore results could be altered. Moreover, low percentages of fibrate treatment
raise a question.
4) Discussion: A reference is required for the sentence ”Despite prior investigations identifying
that as many as 30% of patients with PBC may have never received treatment with UDCA..”
Other than the above, the study is well written and provides significant information about use of
UDCA based on real world experience. Therefore, my final decision is to accept the publication
with some improvements.
Review for 10.1186/s12876-023-03108-4 (2024)

Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 5 Date: 10 Nov 2023
Reviewer's report:
In their revised version, in my opinion the authors did not provide lacking informations  to
draw firm conclusions. Among patients who were not taking UDCA, there were patients on
OCA monotherapy due to intolerance of UDCA, however reasons for UDCA intolerance are
not reported as well as which dose was not tolerated and there were 16 patients who were either
not on therapy for UDCA ("due to poor adherence, lack of follow-up, never prescribed, etc.")
or there was inadequate documentation to confirm whether their PBC had ever been treated.”
Moreover,  it was not possible to follow patients in order to assess their response to treatment,
thus the factors that may affect this were not considered in data analysis and patients with
autoimmune hepatitis/PBC overlap syndrome were not excluded. Even if the use of UDCA is
indicated in PBC/AIH overlap patients, this is a different clinical entity potentially affecting the
results of the study.
Review for 10.1186/s12876-023-03108-4 (2024)

Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 5 Date: 25 Nov 2023
Reviewer's report:
In this study McDonald et al, analyzed records from a large urban health system with
regards to medications. Accordingly, they managed to quantify candidacy and usage rates
of pharmacotherapy in patients with an established diagnosis of PBC. Of interest, an almost
universal compliance to UDCA prescription and treatment guidelines and was noted.
The study is well-written, several limitations have been already recognized by the authors and
questions raised in the previous draft have been satisfactory answered. Therefore, my final
decision is to accept it for publication.
Review for 10.1186/s12876-023-03108-4 (2024)

Title: Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication
Candidacy and Rates of Treatment
Version: 6 Date: 26 Dec 2023
Reviewer's report:
In this study McDonald et al, analyzed records from a large urban health system with regards
to medication for PBC. Accordingly, they managed to quantify candidacy and usage rates of
pharmacotherapy in patients with a reported diagnosis of PBC. Of interest, an almost universal
compliance to UDCA prescripton and treatment guidelines was noted.
Several limitations have been already recognized by the authors and my questions
raised in the previous draft have been satisfactory answered. Therefore, my final decision is to
accept it for publication.
Review for 10.1186/s12876-023-03063-0 (2024)

Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 3 Date: 13 Jun 2023
Reviewer's report:
1- The title does not fit with the study design (HARM was not used in the diagnosis of rectocele),
instead, it will be more appropriate if the title was about the assessment of anorectal physiology
in rectocele patients compared to healthy subjects.
2- The authors mentioned the term "moderate rectocele" in the abstract (background paragraph).
How can they define moderate rectocele?
3- In the abstract (results paragraph), the term "randomly assigned" was used despite the study's
retrospective nature.
4- The term "prognosis" was used multiple times in the manuscript in a confusing way. What is
meant by "prognosis"? Do the authors mean “progress” instead?
5- In the introduction: rectocele may be defined as herniation of the rectal wall through the
rectovaginal septum, but it cannot be described as a hernia or a mass.
6- On page (4), in the 2nd paragraph, sentences starting from “few studies ..." until the end of
the paragraph have no reference.
7- On the same page (4), the 4th paragraph is almost the same as the 3rd one.
8- The construction of the term "healthy subjects in women" is strange and requires modification.
9- The side heading (1.2) should refer to healthy subjects or volunteers.
10- In the "patient inclusion criteria" paragraph, why the authors included pathologies other
than rectocele? This action will result in a loss of direct relation between the results and the
rectocele as the other pathologies will interfere with these results. in this case, subgroup analysis
is mandatory.
11- In the "patient exclusion criteria" paragraph, I am not familiar with the term "fecalography".
Also, the meaning of the word "incompatibility" is not fully comprehended.
12- On page (7), in the 2nd paragraph, a reference to this information is required.
13- In the same paragraph, what is the reference value to the defecation index?
14- In the results section: again, the inclusion of cases of rectocele associated with other
pathologies will interfere with the results.
15- Under the side heading 2.2.2: it is important to clearly describe the degree of correlation.
(r=-0.28) can be described as weak, while (r=0.40) can be described as moderate).
16- In the "discussion" sector, page 10, in the first paragraph, after mentioning the results of
previous, what are the similarities and the differences between the results of your study and
previous studies and how can you explain them?
17- In the 2nd paragraph, I could not fully comprehend the sentence starting with "as a result,
the sensitivity of the RAIR ....".
18- Generally, it was important to assess ODS symptoms in patients using a valid score and to
test the correlation between this score and the manometry results in the patient group.
Review for 10.1186/s12876-023-03063-0 (2024)

Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 5 Date: 16 Jul 2023
Reviewer's report:
Thank you for your effort. However, a few points still require attention:
1. The title is flawed. I suggest the following title "High-Resolution Anorectal Manometry in the
Diagnosis of Obstructed Defecation Syndrome due to Moderate Rectocele Compared to Healthy
Subjects".
2. The points (3, 9, 13, and 15) were not addressed.
3. I cannot find where you mentioned the Cleveland Clinic score of the PAC-QoL system.
4. The results paragraph in the abstract is too long.
5. The results section is too long. You can summarize it with reference to the tables.
6. Language requires more attention. I suggest using a grammar correction and writing assistance
platform like Grammarly.