JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-021-02024-9 (2022)

Title: Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible
with clinical-pathologic grounds) during the COVID-19 pandemic – an observational case-
control study.
Version: 3 Date: 18 Sep 2021
Reviewer's report:
Dear Authors,
I enjoyed your manuscript. It's a well design study, with an adeguate sample size.
In my opinion i add and comment some references that showed a huge sample, and could give
a broader view of your manuscript:
- Ielpo B, Podda M, Pellino G, Pata F, Caruso R, Gravante G, Di Saverio S, on behalf of the ACIE
Appy Study Collaborative. Global attitudes in the management of acute appendicitis during
COVID-19 pandemic: ACIE Appy Study. Br J Surg. 2020 Oct 8. doi: 10.1002/bjs.11999
- COVIDSurg Collaborative and GlobalSurg Collaborative. Timing of surgery following SARS-
CoV-2 infection: an international prospective cohort study. Anaesthesia Mar 2021 doi:10.1111/
anae.15458
- Lisi G, Campanelli M, Mastrangeli MR, Grande S, Viarengo MA, Garbarino GM, Vanni G,
Grande M. Acute appendicitis in elderly during Covid-19 pandemic. Int J Colorectal Dis. 2021
May 27. doi: 10.1007/s00384-021-03959-x
Review for 10.1186/s12876-021-02024-9 (2022)

Title: Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible
with clinical-pathologic grounds) during the COVID-19 pandemic – an observational case-
control study.
Version: 3 Date: 27 Sep 2021
Reviewer's report:
Thank you for the opportunity to review this manuscript from a prominent hospital in Isreal,
one of the leaders of the COVID-19 pandemic in terms of containment response and vaccination
speed.
The manuscript highlights that a delayed presentation due to the pandemic has resulted in worse
clinical state of the appendicitis disease process but did not yield any difference in the surgical
outcomes.
As brought up earlier in my point-for-point assessment checklist, the COVID-19 pandemic is a
global phenomenom and diseases, infective or neoplastic would undoubtedly present later. This
is in part due to patient and healthcare factors. A disease presenting later would definitely have
an impact on the extent of disease down its line of natural progression and simply highlighting
that the pandemic results in later presentation and worse extent of appendicitis is not going to
help literature in any way.
I would have like the authors to highlight the barriers for presentation delay, and pair that up
with the worse clinical manifestation in order to assist readers to take the necessary steps to
address this delayed presentation.
Review for 10.1186/s12876-021-02024-9 (2022)

Title: Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible
with clinical-pathologic grounds) during the COVID-19 pandemic – an observational case-
control study.
Version: 6 Date: 07 Nov 2021
Reviewer's report:
Thanks for addressing the comments.
No further comments from me.
Thank you.
Review for 10.1186/s12876-022-02099-y (2022)

Title: Association between the cardiometabolic index and non-alcoholic fatty liver disease:
insights from a general population
Version: 0 Date: 29 Aug 2021
Reviewer's report:
Dr. Jiawang Zou et al. have reported that higher cardiometabolic index (CMI) has independent
association with NAFLD risk in the general population. They use big data and analyze them in
detail. This study is an interesting study that can find NAFLD patients in the general population
using CMI, which calculated as Waist-to-height ratio (WHtR) multiplied by TG/HDL-C ratio.
I have some questions and comments, however, that I believe the authors need to address, as
follows:
1. Wakabayashi I et al. reported (Clin Chim Acta. 2015) that CMI is repeatable marker for the
effective identification of hyperglycemia and diabetes. They showed the cutoff values of CMI
for hyperglycemia and diabetes were determined to be 0.799 and 0.800, respectively, in women
and to be 1.625 and 1.748, respectively, in men.
In this manuscript, the authors showed that there is a strong positive correlation between higher
CMI and the risk of NAFLD in the general population.  If so, they should indicate a cutoff value
for CMI to determine NAFLD.
2. Based on the results of this study, can waist circumference, height, triglycerides, and HDL
cholesterol (CMI) be used to diagnose NAFLD non-invasively, and how accurate can it be said
to be?
3. The authors have often analyzed the relationship between CMI and NAFLD, but have they
analyzed the relationship with fibrosis using, for example, the FIB-4 Index? If so, the data should
be presented.
1. Please change ‘WhtR’ in line 2 on table 1, to ‘WHtR’.
Review for 10.1186/s12876-022-02099-y (2022)

Title: Association between the cardiometabolic index and non-alcoholic fatty liver disease:
insights from a general population
Version: 0 Date: 02 Nov 2021
Reviewer:  Hirokazu Takahashi
Reviewer's report:
The authors investigated the association between cardiometabolic index (CMI) and nonalcoholic
fatty liver disease (NAFLD) in the health checkups cohort.
Comments
1. Method. The reason why the authors excluded the subjects who had diabetes and/or impaired
fasting blood glucose is totally unclear. Please explain in detail.
2. Ethics. Page 4, line 17-20. Whereas the subjects were anonymized, and main study has been
approved by IRB, the authors should show the approved number of the study protocol for human
study. Please show the information about approved number of the protocol (main study) and
name of IRB.
3. Page 9, line 4. “These research data provide a new idea for the non-invasive evaluation of
NAFLD and are of great significance.” This is out of purpose of the current study. If so, The
authors should perform the ROC analysis and compare the established non-invasive evaluation
method like fatty liver index.
4. Table 2. Title. What does “AAPR” stand for?
5. Several brackets and unit (%) are missing in Table 1.
6. Page 4, line 2. Bracket for citation 22-25 is missing.
Review for 10.1186/s12876-022-02095-2 (2022)

Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 0 Date: 03 Jul 2021
Reviewer's report:
Although the authors studied various subsets of patients with HEV infection the presenting
clinical phenotypes are a major confounder. ALF patients are grouped together with ACLF
presentations under a label of "liver failure" and compared to healthy controls and patients with
HEV hepatitis only. The different serum levels may not be at all HEV disease/presentation
specific, but merely features of cholestatic liver disease of all etiologies. It would have been
advisable to have a non HEV control group of "liver failure" patients.
Looking at the Kaplan Meier curve and individual SOD levels measuring >400 it looks as though
that only a small number in the ALF group had a level above 400. The number of patients above
the cutoff level should have been provided.
Liver failure is not always an inflammation mediated hepatocellular injury process as stated in
"Background".
The definition of "liver failure" 2nd paragraph Background section is inadequate.
At what time points were the measurements taken and were these timings identical in relation
to disease progress and presentation between groups? Where any patients in the ACLF or ALF
groups transplanted, if so how was the data for transplanted patients analyzed/censored?
What was the rationale to measure serum rather than tissue levels from biopsy data? This should
be explained.
There are a number of language and expression errors - too many to individually list them all.
Appropriate language revision and editing is required. In the abstract and under Methods the
authors state that SOD levels were estimated - surely and given the elaborate lab tests performed
they must have been measured!
In Results 1st sentence "HEV induced liver failure patients showed increased SOD levels
compared with...
Background first paragraph it is countries rather than counties, the whole sentence would need
revising. Likewise the 2nd paragraph in this section would require rephrasing.
It should read HEV ACLF on the background of rather than patients based on ALD or CHB.
Review for 10.1186/s12876-022-02095-2 (2022)

Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 0 Date: 05 Nov 2021
Reviewer:  Premashish Kar
Reviewer's report:
For establishing the diagnosis of HEV infection ,did u include IGM antihev and HEV RNA
positivity or either of them .This is not clear from this paper .HEV leads to oxidative stress and
HMGB1 release which causes apoptosis of the hepatocytes .In this hypothesis the author tried
in the same sample size which could have been a different study.How does the authors explain
the remission of the SOD levels in the remission stage compared to the progressive stage
Review for 10.1186/s12876-022-02095-2 (2022)

Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 2 Date: 30 Nov 2021
Reviewer:  Premashish Kar
Reviewer's report:
I've gone through the revised manuscript which has incorporated changes suggested by me and
I think the paper could now be considered for acceptance if the editorial board agrees.
Review for 10.1186/s12876-022-02095-2 (2022)

Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 2 Date: 06 Dec 2021
Reviewer's report:
Many of my previously posed questions have been dealt with satisfactorily.
I would disagree with the comment that tissue cannot be used for diagnosis due to the risks
associated with biopsy and esp looking at the severity of disease esp in the ALF cohort (severity
of coagulopathy). TJ biopsy can be safely performed in ALF and coagulopathic patients; the
main problem is around sampling errors/diagnostic yield in case an area of necrosis is biopsied,
this may not be relevant in relation to SOD levels though.
Are there any animal experiments regarding tissue SOD levels in ALF? If so this should be
referenced.
In the  Methods and Result sections "HEV on the ground of ALD, CHB" should be changed  to
"on the background of ALD, CHB" and throughout the manuscript.
AUROC curves and levels should be provided for SOD, the area under the ROC curves don't
look as though there is a very specific and sensitive cutoff value which could be used as a
prognostic indicator, which is somewhat one of the main goals of the paper.
The definition of ALF in the Introduction is poor - page 3 last sentence; the same definition as
per the later quoted APASL criteria or other commonly used definitions should be used "Bernal
et Wendon NEJM Dec 2013".
Do the authors think that the SOD levels are predominantly linked to organ failure and given
the difference ACLF vs ALF. Were the decompensated ACLF patients sicker in terms of MOF
which would also explain the high mortality? Are SOFA scores or other organ failure scores
available?
In other words is SOD just a marker of organ failure and associated ROS activation, rather than
HEV specific - this could be briefly appraised  in the Discussion and as a possible confounder.
Review for 10.1186/s12876-021-02087-8 (2022)

Title: Remote-controlled cholangiography injection device: First clinical study in China
Version: 3 Date: 24 Oct 2021
Reviewer's report:
The authors should be commended for the cleverness of this device. I do believe that it shows
promise and could be a game changer for those who administer contrast.
I did find that I had to read the manuscript twice in its current form in order to understand it. Part
of it is grammar and style. Examples include the conclusion paragraph of the abstract. Contacting
patients telephonically instead of by phone, etc.
The design of this study needs to be clarified. Is this a retrospective review of a prospective
database? Please clarify.
I recommend that the authors clearly state from the beginning that all patients had percutaneous
biliary tubes. While it may be intuitive to some, it may be confusing for others.
It is unclear to me why ERCP is not mentioned in this manuscript as a way to assess the biliary
system?  While not the essence of the paper, the authors do discuss other modalities to evaluate
the biliary system.  I think this should be included.
There were other limitations of the manuscript including its retrospective design?! Please
elaborate.
Review for 10.1186/s12876-021-02087-8 (2022)

Title: Remote-controlled cholangiography injection device: First clinical study in China
Version: 3 Date: 03 Nov 2021
Reviewer's report:
I read with interest your paper about remote controlled cholangiography injection and i
believe could be usefull expecially in high volume epatobiliary department.My question is:do
you suppose its use for intraoperative cholangiography both in open and laparoscopic way? Can
you mention this aspect in your paper?
Review for 10.1186/s12876-021-02087-8 (2022)

Title: Remote-controlled cholangiography injection device: First clinical study in China
Version: 3 Date: 03 Nov 2021
Reviewer's report:
The work appears well done and the proposal appears interesting.
There is no doubt the advantage for the reduction of the X-ray exposure of the operators during
the drainage check. Perhaps the major limitation could be represented by the lengthening of the
timing given by the injector set-up, compared to the traditional manual control. This proposal
could find a future space in checks carried out on an outpatient basis. However, the experience
remains monocentric, a broader and more multicentre enrollment is desirable.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 1 Date: 20 Sep 2021
Reviewer's report:
The subject of the manuscript is very novel and can guide the treating psychiatrists to be vigilant
about physical illnesses and general health of patients with schizophrenia.
But there are some issues.
The language and expression are very poor and needs to be rewritten. Word schizophrenic is not
appropriate, it should be persons with schizophrenia.
Methodology is not described properly. Who diagnosed the patients? Were there any
physiological tests and who made the diagnoses of schizophrenia
No mention of informed consent or ethics committee approval.
Why logistic multiple regression used,the presentation of regression in the table is also not
appropriate.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 1 Date: 16 Oct 2021
Reviewer's report:
Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction
This is a retrospective study to examine the clinical characteristics and related risk factors of
schizophrenia patients with intestinal obstruction.
In background section
1. The authors did not review any article related to intestinal obstruction in schizophrenia.
Therefore, the context for the research question addressing in this study is not clear.
In methods section
1. There are many reports of intestinal obstruction following treatment with combination of
antipsychotics and anticholinergic drugs in the literatures. However, the authors did not include
any medications in the analysis, such as antipsychotics, anticholinergic agents which could also
increase the risk of intestinal obstruction.
2. The authors did not provide the rationales for selection of the main observation indicators and
the definition they selected. For example, age #60 years old and #60 years old; Hospital stay
#90 days and #90 days; Course of disease#5 years and #5 years; Visiting time#24 hours and
#24 hours in table 1.
3. According to the definition, the incidence rate is the number of new cases within a time period
(the numerator) as a proportion of the number of people at risk for the disease (the denominator).
However, the authors did not mention the time period.
In results section
1. The authors did not provide the whole samples’ demographic characteristics, such as average
age.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 1 Date: 18 Oct 2021
Reviewer:  Valentin Matei
Reviewer's report:
In the background the authors failed to offer the readers information about intestinal obstruction
in normal population (which would be very important in order to understand if the risk are
different between schizophrenia patients and controls.  Also there is not a proper presentation
of the data regarding intestinal obstruction in schizophrenia patients (instead authors stated
bluntly that “there are still few studies on the clinical characteristics and related risk factors of
schizophrenia patients with intestinal obstruction” without citing any of papers of interest for
the topic at hand.
One of the most important risk factors for intestinal obstruction in schizophrenia patients is
medication (an especially clozapine use Susanna Every-Palmer, Mike Nowitz, James Stanley,
Eve Grant, Mark Huthwaite, Helen Dunn, Pete M. Ellis, Clozapine-treated Patients Have
Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal
Complications: A Cross Sectional Study, EBioMedicine,
Volume 5, 2016, Pages 125-134). The authors didn’t analyze at all the putative role of
treatment even though they acknowledged the importance of treatment as risk factor for
intestinal obstruction in discussion part: “5) The anticholinergic effect of drugs for the treatment
of schizophrenia can inhibit the contraction of gastrointestinal smooth muscle and reduce
gastrointestinal secretion and peristalsis. Therefore, the longer the course of the disease, the
longer the medication time, and the greater the dosage, the more frequent the patient’s intestinal
obstruction.”
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 1 Date: 19 Oct 2021
Reviewer:  Takefumi Suzuki
Reviewer's report:
In this retrospective study of 1937 Chinese patients with schizophrenia it was found that
intestinal obstruction was noted in 97 patients (5.01%); 65 were treated surgically and six
people died. Such factors as older age, longer hospital stay, longer course of the disease,
history of previous abdominal surgery, male gender and delayed medical attendance were
found to increase the risk of intestinal obstruction. However these risk factors are well-known
and not particularly novel. Functional intestinal obstruction (or ileus) that frequently results
from chronic constipation is a highly relevant issue in the management of schizophrenia in
light of its high prevalence (doi: 10.1186/1471-230X-11-17). Ileus is likely to be recurrent
(doi: 10.1016/j.genhosppsych.2015.09.003) and constipation is oftentimes missed in clinical
practice (doi: 10.1016/j.genhosppsych.2013.06.007). It may also be well possible that some
physical mechanisms (e.g., adhesion from past abdominal surgery) may complicate the clinical
picture. Further refractory constipation may result in intestinal perforation (doi: 10.1345/
aph.1S117), a life-threatening medical condition. Lowered sensitivity to pain in patients with
schizophrenia (doi: 10.1097/00131746-200603000-00004) may at least in part account for the
occurrence of intestinal complications in this specific population. In this work mechanisms
of intestinal obstruction (i.e., functional or organic) remain unclear. Also unclear is possible
contribution of medications (e.g., laxatives and drugs with anticholinergic effects); dose
reduction of antipsychotics for instance may alleviate persistent constipation (doi: 10.1111/
j.1365-2710.2007.00843.x). Good clinical practice is to recommend physical activities, fluid
and dietary fiber intake in order to counteract intestinal hypomotility, which may be somewhat
difficult for people with schizophrenia in general. Possible effects from smoking may also be
considered (doi: 10.1080/14622200701188919). The authors may want to incorporate the above-
mentioned issues in the text. No further comments.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 2 Date: 20 Dec 2021
Reviewer's report:
the authors answer all of my comments and have made revision.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 2 Date: 27 Dec 2021
Reviewer's report:
The study has improved a lot after addressing all reviewers' comments.
Only one point which still needs to be addressed is language and use of word Schizophrenic.
We should say persons with schizophrenia.
Review for 10.1186/s12876-021-02091-y (2022)

Title: Study on Clinical Characteristics and Related Factors of Schizophrenia Patients with
Intestinal Obstruction Running title: Schizophrenia with Intestinal Obstruction
Version: 2 Date: 27 Dec 2021
Reviewer:  Takefumi Suzuki
Reviewer's report:
The authors may want to change the title of the manuscript and the short title to "Clinical
Characteristics and Related Factors of Patients with Schizophrenia Complicated with Intestinal
Obstruction" and  "Intestinal Obstruction in Schizophrenia ", respectively. No further comments.
Review for 10.1186/s12876-021-02075-y (2022)

Title: The association of zonulin-related proteins withprevalent and incident inflammatory
bowel disease
Version: 2 Date: 09 Nov 2021
Reviewer's report:
Please see https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210728 and
comment on the utility of ELISA test you used
Review for 10.1186/s12876-021-02088-7 (2022)

Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 2 Date: 28 Sep 2021
Reviewer:  Takafumi Osaka
Reviewer's report:
The correlation of circulating total bilirubin (TB) and UGT1A1 with NAFLD in the Chinese Han
population has been well validated. In particular, the use of MRI-PDFF in all cases is excellent.
However, some corrections and additions are needed.
1. In reference 16, grades 2-3 are defined as MRI-PDFF # 21.7%, but the authors use 21.6%.
2. The authors define high TB as (TB >17.1) and high ALT as (ALT >45), but do not specify
the basis for their definition.
Review for 10.1186/s12876-021-02088-7 (2022)

Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 2 Date: 07 Oct 2021
Reviewer's report:
Comments to the Author
In this study, the authors investigated the association between circulating TB /UGT1A1 and
liver fat fraction. Hepatic steatosis severity examined by MRI-PDFF was valuable and focusing
UGT1A1 besides total bilirubin was the novelty of this study. However, there is a lack of
assessment to understand the mechanism of the positive correlation of TB/UGT1A1 with fat
fraction. I have some comments and queries:
Major
1) The authors investigated circulating UGT1A1 and found correlation with fat fraction in the
NAFLD patients with severe steatosis. While the function of UGT1A1 in liver tissue especially
regarding gene variants has been well discussed so far, the meaning of calculating UGT1A1 in
blood is not elucidated. Are there any previous studies which looked at the circulating UGT1A1?
The authors should discuss the mechanism underlying elevated amount of UGT1A1 in blood.
2) Although a fair amount of previous study showed that serum bilirubin levels are inversely
associated with development of NAFLD/NASH as the authors described, this study found TB
was higher in the patients with moderate and severe steatosis. I suggest the author discuss why
the present study showed the different result from the previous reports which showed inversely
association between TB and NAFLD. In addition, investigating direct bilirubin and indirect
bilirubin would be valuable especially discussing the relation with UGT1A1 in this study.
3) The author presented cutoff value of TB and UGT1A1 on NAFLD. However, AUROC was
very low and predictive power is too weak to show cutoff value.
4) Are there any correlations between TB/UGT1A1 and co-varieties such as age, sex, BMI, and
ALT? In addition, Is there correlation between TB and UGT1A1?
Minor
1) p9 in Discussion, “Previous studies reported the association of circulating TB levels with the
risk of NAFLD or NASH.” the citation for this description should be included.
2) The results of correlation between liver fat fraction with TB/UGT1A1 (with prevalence of
NAFLD, with grades of steatosis and in groups stratified by TB and so on) were distributed to
Table 2,3,4,6. It is recommended to organize and present the results in fewer numbers of tables.
Review for 10.1186/s12876-021-02088-7 (2022)

Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 4 Date: 03 Dec 2021
Reviewer:  Takafumi Osaka
Reviewer's report:
It's well fixed, no problem.
Review for 10.1186/s12876-021-02088-7 (2022)

Title: Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the
development of non-alcoholic fatty liver disease: a cross-sectional study
Version: 4 Date: 05 Dec 2021
Reviewer's report:
The authors have addressed the concerns adequately.
Comments to the authors
1) In the absence of the data of direct bilirubin and indirect bilirubin of the subjects, the authors
should discuss failure as one of the limitations of the study design in terms of this study
investigated UGT1A1 that glucuronidates bilirubin.
2, The authors described the severity and the incidence of NAFLD in this study as “the risk”
of NAFLD in the title and results. However, the present study design was cross-sectional and I
think the expression of “the risk” is inaccurate.
3, It is better to check the spelling and grammar of text in the document;
"The inconsistent results of the association between circulating TB and the risk of NAFLD may
due to the diagnstic method of NAFLD and the genetic background of subjects. "
Review for 10.1186/s12876-021-02083-y (2022)

Title: Real world evidence of the association between medication and life expectancy in elderly
inflammatory bowel disease: a population-based cohort study
Version: 1 Date: 09 Oct 2021
Reviewer's report:
Review:
This is an interesting original article about the “ Real world evidence of the association between
medication and life expectancy in elderly inflammatory bowel disease: a population-based
cohort study „
The authors were using the Ontario population-based health administrative data base to describe
the life expectancy associated with IBD therapies in elderly patients.
This is well written, interesting article, the figures are made well, easily understand.
I only have one minor suggestion
1. The introduction a bit short, it would be preferable to extent a bit.
Review for 10.1186/s12876-021-02083-y (2022)

Title: Real world evidence of the association between medication and life expectancy in elderly
inflammatory bowel disease: a population-based cohort study
Version: 1 Date: 17 Oct 2021
Reviewer's report:
It is an excellent study well-written and presented. It allows the reader to conclude the life-
expectancy fo elderly IBD patients receiving various medications.
If possible, the inclusion or a graph about life expectancy under various medications would make
the paper more attractive.
Review for 10.1186/s12876-021-02083-y (2022)

Title: Real world evidence of the association between medication and life expectancy in elderly
inflammatory bowel disease: a population-based cohort study
Version: 3 Date: 20 Dec 2021
Reviewer's report:
This is a well-written manuscript aiming to elucidate the association of  life expectancy in people
with inflammatory bowel disease (IBD) and different types of
IBD therapies.  The limitations of the study  are described by the authors. Comorbid diseases
and disease severity play a fundamental role, but the life expectancy  under different types of
treatment is a piece of information always interesting to know.
Review for 10.1186/s12876-021-02073-0 (2022)

Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 20 Sep 2021
Reviewer:  Maikel Peppelenbosch
Reviewer's report:
- Although well intelligible, the text could do with a (further) proofread.
- The introduction would benefit from a short summary of current clinical management
on the development and prevention/treatment  of [early] gastric cancer, before noting that
gastric cancer is still a leading cause of cancer-related death, e.g, by refering to a recent
guideline (Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the
Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
Aug 25:S0016-5085(21)03236-4. doi: 10.1053/j.gastro.2021.06.078) and review  (Waddingham
W, Nieuwenburg SAV, Carlson S, Rodriguez-Justo M, Spaander M, Kuipers EJ, Jansen M,
Graham DG, Banks M. Recent advances in the detection and management of early gastric
cancer and its precursors. Frontline Gastroenterol. 2020 Jul 30;12(4):322-331. doi: 10.1136/
flgastro-2018-101089).
- How specificity of PSPH staining was ascertained is not clear from the manuscript.
- It is unclear whether wether one-sided or two-sided statistical testing was performed
- Discussion: specific types of gastric cancer are characterised by differential sensitivity to
immunotherapy (Kodach LL, Peppelenbosch MP. Targeting the Myeloid-Derived Suppressor
Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best
Limited to Specific Subtypes of Gastric Cancers. Gastroenterology. 2021 Aug;161(2):727. doi:
10.1053/j.gastro.2021.03.047) and may also display different levels of PSPH expression. This
should be discussed.
- Discussion: mechanistic discussion on how PSPH interacts with gastric cancer cell
physioliology should be included. PSPH is clearly implicated in autophagy (Zhang J, Wang E,
Zhang L, Zhou B.. PSPH induces cell autophagy and promotes cell proliferation and invasion
in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway.
Cell Biol Int. 2021 Feb;45(2):305-31) which is important in gastric cell physiology and the
interaction with Helicobacter, as evident from genetic polymorphisms in the population that
predispose to the disease (Mommersteeg MC, Yu J, Peppelenbosch MP, Fuhler GM. Genetic
host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms. Biochim
Biophys Acta Rev Cancer. 2018 Jan;1869(1):42-52. doi: 10.1016/j.bbcan.2017.11.00).
Review for 10.1186/s12876-021-02073-0 (2022)

Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 22 Sep 2021
Reviewer's report:
This is an interesting study based on a sufficient sample size, but there are some concerns that
should be addressed.
1. In the chapter "High PSPH level indicates poor prognosis in gastric cancer", the authors refer
to Table 3 and describe PSPH expression as a risk factor.
This is considered to be an exaggeration. The fact is that it was significant in univariate analysis,
but no longer so in multivariate analysis.
It is possible that High PSPH is a risk factor, but it cannot be stated definitively, and the wording
should be revised.
2. In the statistical analysis, it is stated that the Wilcoxon signed rank test was used, but the
comparison of PSPH high vs PSPH low should be unpaired. This is an inappropriate method.
3. In Table 3, the cutoff for age is 59 years. This is a strange value, but why was it set at this
value? There is no explanation in the paper, so please add an explanation.
Review for 10.1186/s12876-021-02073-0 (2022)

Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 05 Oct 2021
Reviewer's report:
Thank you for giving me the opportunity to review your interesting manuscript titled, "
Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and its
potential association with immune cells”
I have some questions and comments.
# I cannot understand the mechanism of the relationship between upregulation of PSPH and
poor survival of gastric cancer patients. Please explain the mechanism in gastric cancer. Is this
only due to low infiltration of immune cells in gastric cancer tissue?
# Please explain the reason precisely for the relationship between high expression of PSPH of
gastric cancer cell and low infiltration of immune cells in gastric cancer tissue.
#  Please explain about the relationship between expression of PSPH and the difference of the
subtype of immune cells infiltrated in gastric cancer.
# Although it is well known that the prognosis of diffuse type gastric cancer is worse than
intestinal type because of distant metastasis especially peritoneal metastasis is common in
diffuse type, almost 65% of diffuse type gastric cancer shows low expression of PSPH,
which showed better prognosis than high PSPH expression group. Please explain about this
contradiction.
# Although in Result the author described that “High PSPH level indicates poor prognosis in
gastric cancer”, PSPH expression was not identified as prognostic factor in multivariate Cox
analysis. I think that the author should not describe as “High PSPH level indicates poor prognosis
in gastric cancer”
Minor Point
# In Method PSPH expression score was divided as negative and positive, while in Result and
Table2 PSPH expression was described as low and high.
Please unify the expression.
Review for 10.1186/s12876-021-02073-0 (2022)

Title: Phosphoserine Phosphatase as a prognostic biomarker in patients with gastric cancer and
its potential association with immune cells
Version: 0 Date: 11 Oct 2021
Reviewer's report:
In this study, Ma-Yan Huang  et al analysed PSPH expression across multiple cancers using
Pan-Cancer data and focused on the relationship between PSPH expression and gastric cancer.
These results indicated that differential expression of PSPH may contribute to survival of
patients with gastric cancer.
The authors did a good job, it is clearly written and the data is meaningful and understandable
the authors should focus on the relationship between differential expression of PSPH in gastric
intestinal and diffuse type carcinoma, then do the analyzes also done on gastric intestinal and
diffuse.
In order to better understand the differences that may exist in PSHA expression in gastric
intestinal and diffuse.
Review for 10.1186/s12876-022-02486-5 (2022)

Title: Procalcitonin in early allograft dysfunction after orthotopic liver transplantation: A
retrospective single centre study
Version: 1 Date: 22 Jul 2022
Reviewer's report:
Frick et al report on the impact of early allograft dysfunction and Ischemia reperfusion injury
on early post transplant procalcitonin levels. This is a single center retrospective study of 110
patients who underwent LTx between 2016 and 2020. The authors report higher levels of peak
procalcitonin levels in patients developing EAD and IRI, but better graft survival in patients with
IRI who have elevated procalcitonin levels. The authors suggest that procalcitonin can serve as
an early marker of adverse outcomes in patients manifesting IRI.
The hypothesis is interesting and needs further study in larger studies.
1. The present study itself has drawbacks due to its retrospective nature, significant missing data
and significant skewing of patient enrolment towards sicker recipients.
2. The key point appears to be the inability of the graft liver to produce procalcitonin despite
significant IRI is a predictor of graft loss. Were there any differences in donor or graft parameters
between IRI+PCT<15 and IRI+PCT>15 groups which could have predicted worse outcomes.
3. In Table 4, nearly half of recipients needed RRT in the post-operative period. This is a very
high incidence of RRT? Does this affect Procalcitonin levels?
4. How the authors explain the high incidence of reoperation and arterial complications, which
are essentially surgical complications in the EAD group. Does a proinflammatory milieu
increase risk of these complications?
Review for 10.1186/s12876-021-02043-6 (2021)

Title: TITLE: Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative
colitis compared to oral tacrolimus
Version: 1 Date: 30 Sep 2021
Reviewer's report:
I've read the manuscript entitled "Intravenous tacrolimus is a superior induction therapy for
acute severe ulcerative colitis compared to oral tacrolimus" with great interests. Clinically, it
is very important to evaluate the efficacy of intravenous TAC for ASUC compared with oral
TAC. Because, as the authors mentioned, intravenous TAC could reach high trough level of
TAC faster resulting in improving clinical course of ASUC. However, I consider that there are
several problems in this paper for publication for BMC Gastroenterology.
Q1. Please describe the reason about the difference of the targeted trough level of TAC between
intravenous and oral TAC treatment.
Q2. Please describe the transition of TAC trough level for not only one week but also two weeks
in both intravenous and oral TAC treatment groups, because the authors evaluated the clinical
response and remission rate at week 1 and 2.
Q3. According to the data, I considered that the difference of clinical remission and response
rate between oral and intravenous TAC treatment groups would be due to the difference of the
targeted trough level of TAC. Therefore, if the target trough level of TAC in oral TAC treatment
group could be much high as like intravenous TAC group, clinical response and remission rate
would be improved. What do the authors think about that?
Q4. I considered that, as mentioned above, TAC trough level but not TAC administration method
might play an important role in clinical course. How about the clinical response and remission
rate stratifying the trough level of TAC at week 1 and 2?
Q5. I considered that, according to colectomy free survival data, the significant difference of
colectomy free survival at within week 5 would contribute to the difference of colectomy free
survival date at week 24 between intravenous and oral TAC treatment groups. Therefore, for
urgent cases like ASUC, how to reach at very high trough level of TAC (over 15 ng/ml) rapidly
would be very important. How do you think about it?
Review for 10.1186/s12876-021-02043-6 (2021)

Title: TITLE: Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative
colitis compared to oral tacrolimus
Version: 1 Date: 03 Oct 2021
Reviewer's report:
Shimizu H. et al. conducted a prospective cohort study to evaluate the effect of intravenous TAC
for acute severe Ulcerative colitis (ASUC). Although many biologics are available for moderate
to severe UC, treatment strategy for ASUC is limited. In that situation, authors showed that the
improvement of endoscopic finding by intravenous TAC resulted in the high colectomy-free
survival rate. It is very intriguing to suggest the new treatment option for ASUC, however, there
are several concerns in this work.
1.
This study should be more focused on the escape from colectomy in short term by intravenous
TAC. Kaplan-Meier curve of colectomy-free survival looks the better effect of intravenous TAC
compared to oral TAC at 2-5 weeks. How about the statistical analysis at 2-5 weeks?
With regard to the treatment of ASUC, the most important thing is the escape from colectomy
in short term. Therefore, if there is no statistical difference, I suggest that authors re-examine
the data by the propensity score matching analysis.
2.
Authors described that all enrolled patients received corticosteroid iv. Was corticosteroid
administered just before TAC? Are there some patients treated by IFX just before TAC? For
example, I infer that the patients with corticosteroid dependent UC, who had undergone steroid
iv previously, received IFX or TAC after the diagnosis of ASUC.
The hazard ratios for colectomy showed no statistical different in biologic agent failure, but p
value was 0.06. Can you conclude that biologic agents have not had an influence on the outcome
of colectomy?
3.
Some patients receive IFX after TAC administered. Given that the treatment after TAC has
influenced on the clinical course, it would be better to add the treatment after TAC (ex. IFX)
in the multivariable analyses using the Cox proportional hazards model for colectomy-free
survival.
4,
ASUC was defined according to the criteria given by Truelove and Witts as 6 bloody stools per
day and one or more of the following: decreased hemoglobin (10.5 g/dL), elevated erythrocyte
sedimentation rate (30 mm/h), fever (37.8C), or tachycardia (90 bpm). Furthermore, diagnostic
criteria of ASUC require hospitalization.
Does only LI score10< correspond with the criteria of ASUC?
5.
Do authors have any decision criteria for intravenous or oral TAC? Authors should mention
about the criteria.
Review for 10.1186/s12876-021-02043-6 (2021)

Title: TITLE: Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative
colitis compared to oral tacrolimus
Version: 4 Date: 16 Nov 2021
Reviewer's report:
I understood author’s answers to my comments well. It was a little disappointing result that the
short-term effect of intravenous TAC and the influence of previous biologics remained unclear
due to the small samples. However, I think that the results and analysis of this paper are worth
enough to be published in the MBC gastroenterology.
Review for 10.1186/s12876-021-02048-1 (2021)

Title: Development and Validation of a Novel Diagnostic Model for Initially Clinical Diagnosed
Gastrointestinal Stromal Tumors using an Extreme Gradient-Boosting Machine
Version: 1 Date: 20 Oct 2021
Reviewer:  Bo Zhang
Reviewer's report:
This is an interesting and well planned, performed, analyzed and reported review. The sample
size is large considering the rarity of the conditions and conclusions are well funded, based on the
results. The authors developed a novel diagnostic model to further differential diagnose GIST
from other tumors in initially clinical diagnosed gastric GIST patients by analyzing the results
of clinical examinations that most patients should have completed before surgical resection.
The accuracy of model prediction in the validation dataset is 0.73 (0.58-0.88), precision is
0.79 (0.60-0.95), recall is 0.87 (0.67-1.00), and f1-score is 0.82 (0.70-0.92). These results
were not significantly superior to previous studies in which traditional CT features were used.
Furthermore, only two   patients were selected to test the prediction quality of the model at the
Individual Scale, and more patients should be included.
Review for 10.1186/s12876-021-02048-1 (2021)

Title: Development and Validation of a Novel Diagnostic Model for Initially Clinical Diagnosed
Gastrointestinal Stromal Tumors using an Extreme Gradient-Boosting Machine
Version: 1 Date: 23 Oct 2021
Reviewer's report:
In this article, authors developed a novel diagnostic model for clinically diagnosed GIST in
discriminating from other submucosal tumours  and validated its utility. Although there are some
limitations in this prediction model, this paper is well written and I have no criticism on this.
Review for 10.1186/s12876-021-02023-w (2021)

Title: Blood Lead Concentrations Among Pediatric Patients with Abdominal Pain; A
Prospective Cross-sectional Study
Version: 1 Date: 19 Mar 2021
Reviewer's report:
1) Why did the authors choose to assess the prevalence and contributing factors of lead poisoning
only among patients presenting with abdominal pain and only those presenting to two hospitals
that are according to the manuscript referral centers? What about potential subjects who would
not make it to these centers even from the same area served by these hospitals? 2) Further, the
study is not powered enough to answer the research question it aims to answer. 3) Univariate
analysis is not very informative here and should at least be followed up/complemented with
multivariate analysis. 4) The manuscript also needs proofreading for the English language and
some of the language used should also be revised to make sure it is scientifically sound.
Review for 10.1186/s12876-021-02023-w (2021)

Title: Blood Lead Concentrations Among Pediatric Patients with Abdominal Pain; A
Prospective Cross-sectional Study
Version: 1 Date: 22 Jun 2021
Reviewer's report:
ABSTRACT
In methods, change "quired" to "queried"
BACKGROUND
I think the authors should consider reorganizing the background a bit. I found myself wondering
the relevance of this type of inquiry in Tehran at the end of paragraph 2. Paragraph 3 provides
the rationale, but as the reader, I needed this sooner. I would consider including some of this
"why" in paragraph 1 - you don't necessarily need to move all of paragraph 3 forward, but I think
you need to pull the audience in better at the beginning.
METHODS
-Line 6, remove extra space between age and comma
-You mention excessive spices and herbs - what's excessive? How was this asked?
-In the description of the Lead care II device use in the methods, perhaps mention if this is via
fingerprick. Was an alcohol wipe use before hand? (to decrease false positive, remove topical
confounders)
RESULTS
-Can you clarify whether the patients were admitted to either of the two hospitals, or seen in an
outpatient setting (or both)? It's not clear.
-Change sentence 3 (latter half) to say "were from Tehran City and another 78..."
-End sentence 3 after "question". Start next sentence with "Figure 1"
-Decide on consistency with capitalization: Tehran City vs Tehran city
MAP
-Numbers are hard to see in the gray districts (for example, 4, 5, 15). Consider bolding.
DISCUSSION
-The finding elevated BLL was significantly more common in children <5 years is the result
that I care most about based on what you've presented. Somehow I think it gets buried under
other results that are less impactful or meaningful for me
-Did you ask about child hand/mouth behaviors? If not I would be clear that that is an inference
-Ensure that abbreviations are previously spelled out and defined (CDC, GI, for example)
-add space between "abovementioned"
-You may need to define schooling certificate for some readers (equivalent of high school
diploma?)
-"Who were referred" should be phrasing in sentence that starts with Ataee
LIMITATIONS
-Decide of consistency for using colon after heading
-"sample size making" should say "sample size makes"
CONCLUSIONS
-We cannot identify causality based on this study