JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-021-01967-3 (2021)

Title: Regorafenib combined with transarterial chemoembolization for unresectable
hepatocellular carcinoma: a real-world study
Version: 1 Date: 09 Apr 2021
Reviewer's report:
This is a well written study on the association of TACE and systemic therapy for second-line
treatment of patients with HCC refractory to sorafenib or levantinib. Despite its merits, the
study has a major methodological issue regarding to its population selection. 13 patients with
metastatic disease were treated with loco-regional therapy, which is something fundamentally
incorrect!
I do not recomendo the publication of this study in its current form, but I urge the authors to
perform a reanalysis of this material excluding this subgroup of patients. These data are still
relevant, and may prove useful in guiding second-line therapy for patients with HCC.
Review for 10.1186/s12876-021-01967-3 (2021)

Title: Regorafenib combined with transarterial chemoembolization for unresectable
hepatocellular carcinoma: a real-world study
Version: 1 Date: 10 May 2021
Reviewer's report:
This study provides real-world evidence indicating that regorafenib combined with TACE was
beneficial and tolerable in patients with unresectable HCC. This is an important issue but there
are several issues should be clarified and corrected before further processing:
1. Why authors did not analyze the prognostic factors of OS, PFS and TTP with multivariate but
only univariate analysis ? The results of statistical analysis were not convincing.
2. According to definition that P-values <0.05 was considered statistically significant. Therefore,
tumor size seems to be associated with PFS. Please check the sentence is correct or not.
3. Please show the “patients at risk” in figure 2-4.
4. Please check figure 2D is correct or not because it is not compatible with figure legend.
5. In table 1 & 2, please check the sum of patients is equal to total patients including ECOG
status, tumor number, CTP grade, TACE method and regorafenib initial dose.
6. Authors should offer data that TACE combined with Regorafenib could offer better OS, PFS
and TTP than 1st line regimen whether sorafenib or lenvatinib use. Besides, the major limitation
of this study is lack of control group that it’s difficult to convince the readers that TACE
combined with Regorafenib could offer better OS, PFS and TTP than TACE or regorafenib
alone.
7. It’s interesting that higher dose had better prognosis. However, this phenomenon is not seen
from other study (Yoo et al, Liver International 2020). Since initial higher dosage with 120 or
160 mg had better OS, PFS and TTP than lower dosage, why every enrolled patient did not
receive higher dosage in the beginning of treatment ?
Review for 10.1186/s12876-021-01967-3 (2021)

Title: Regorafenib combined with transarterial chemoembolization for unresectable
hepatocellular carcinoma: a real-world study
Version: 3 Date: 25 Sep 2021
Reviewer's report:
No further comments. I recommend this paper for publication, and consider myself very
fortunate for having had the opportunity to learn from the authors.
Review for 10.1186/s12876-021-01963-7 (2021)

Title: Cytokeratin 18 can help predict liver fibrosis in HCV infected patients with type 2 diabetes
mellitus
Version: 1 Date: 01 Sep 2021
Reviewer's report:
The study assessed the value of cytokeratin 18 in the assessment of liver fibrosis in hcv diabetic
patients, however, there are two major concerns:
- Sample size calculation is important for the results to be valid.
- Absence of control group of hcv patients and non diabetic is a major limitation.
Moreover, being a retrospective study may increase the risk of bias.
Review for 10.1186/s12876-021-01977-1 (2021)

Title: Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections
Version: 0 Date: 13 Aug 2021
Reviewer's report:
I have several comments:
1. Please provide one section about probiotic supplementation effect on gut microbiome
during H pylori therapy and include more ref about this issue  e.g. Helicobacter 2016
Dec;21(6):493-503. Microb Pathog. 2017 Aug;109:156-161. Eur J Clin Microbiol Infect Dis.
2020 Jul;39(7):1365-1372.
2.Table 4: Please provide P value or statistical significance in each study. And I don't know if
the following study "Iran J Pediatr. 2013 Feb; 23(1): 79–84." was listed in Table 4
3. Table 5:Please revise the title :"Summary of current meta-analysis on the efficacy of probiotics
in cure of H. pylori infection" The listing study was not meta analysis and may add the term
"adult population "
4. Please re-write abstract. The following sentence "Helicobacter pylori (H. pylori) is one of
the most common causes of bacterial infections worldwide, mostly colonized in the human
stomach during childhood. Chronic infection with this bacterium increases the risk of developing
severe complications such as peptic ulcer and gastric adenocarcinoma. Unfortunately, none of
the available treatment regimens can completely eradicate this pathogen. Factors such as acidic
stomach conditions, trapping of antibiotics in the gastric mucosa, side effects of antibiotics,
dormancy phenomenon, and antibiotic resistance all contribute in reducing the rate of infection
eradication. In recent decades, probiotic therapy has been considered as one of the most desirable
ways to treat the infection of this bacterium."   should be deleted. And please add more concise
and important information focus on probiotic effect on H.P therapy.
Review for 10.1186/s12876-021-01972-6 (2021)

Title: Predictive Scoring Systems for In-hospital Mortality due to Acutely Decompensated Liver
Cirrhosis in Indonesia
Version: 4 Date: 21 Apr 2021
Reviewer's report:
The authors describe a new score, to predict in-hospital mortality in cirrhosis patients. The
identified parameters are in line with recent studies and therefore somehow "expected".
However, some aspects need to be addressed:
- Methods: Some aspects should be described in more detail, especially, what does "missing
data" in the exclusion criteria mean? The authors stated that MELD or ACLF could not be
calculated due to missing data in the included patients?
- Methods: Why are some continuous data transformed into natural logarithm and some (e.g.
SpO2/FiO2) catagorized? How was the cut-off determined?
- Results: Do the authors have information on CRP levels? Was a screening for bacterial
infehcions performed in all patients or only, if clinically indicated?
- Results: The rate on GI-bleeding in surprisingly high. What was the definition of GI Bleeding
in the context of the study and what were the etiologies of bleeding (varicceal bleeding, peptic
ulcer etc).
- A major aspect in interpreting the data and to asses clinical benefit, it would be great to compare
the proposed score to established scores like MELD or ACLF grade. Unfortunately these data
are not available to the authors.
- Addative scoring system: What was the reason to use exactly these categorizations? Was it
based on statistical methods or other aspects?
Review for 10.1186/s12876-021-01972-6 (2021)

Title: Predictive Scoring Systems for In-hospital Mortality due to Acutely Decompensated Liver
Cirrhosis in Indonesia
Version: 6 Date: 07 Jun 2021
Reviewer's report:
THe authors have made several adjustments to the manuscript according to the reviewer
suggestions. I can understand that the INR was not availiable from all patients, but I still think
the MELD-Score and the ACLF grade would be interested, at least in a subgroup, especially as
Bilirubin and creatinine were predictors of death in the cohort, which are included in both, the
MELD and the ACLF grade.
Review for 10.1186/s12876-021-01946-8 (2021)

Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 11 Aug 2021
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- “CD patients”
Patients with CD
- Define what is mucosal healing in CD
- “UST showed ideal efficacy”
Ideal?
- Use the abbreviation in the whole text after the definition (for example for Crohn’s disease)
- Since this is a retrospective study, and you stated “All patients underwent endoscopy prior to
UST initiation and at week 16/20 after UST therapy (approximately the third administration of
UST)”: in your clinical practice that each patients undergo colonoscopy 4-5 months after the
start of a biologic? If this is an inclusion criterion, you have to modify the methods defining
inclusion and exclusion criteria
- Regarding the outcomes (endoscopic and clinical remission): how did you consider the patients
that stopped ustekinumab due to primary failure? How did you consider patients on steroid
therapy at the timepoint of the outcome assessment?
- SES-CD could be calculated in patients with a history of intestinal resection too
- How do you explain a so different ability to predict endoscopic remission respect to clinical
response of trough levels?
- “Therefore, a TDM based on trough concentration is the optimal strategy for patients with
poor response or loss of response to UST therapy.” “UST optimization based on TDM is of core
importance for patients who lose responses”
You can’t state this because you did not prove that a dose escalation of ustekinumab based on
trough levels improved the outcome and you did non analysed the setting of loss of response.
- “Therefore, when patients lose response to UST, therapeutic drug monitoring is of great
importance to ensure that UST treatment can be optimized before switching to other therapeutic
strategies.”
What about performing a dose escalation from 12 to 8 weeks without TDM but based on clinical
parameters?
- Are the results of the kits used in the various studies about trough levels of ustekinumab
comparable or every center must find a threshold according to the kit he uses?
Review for 10.1186/s12876-021-01946-8 (2021)

Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 04 Sep 2021
Reviewer's report:
Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with
refractory Crohn’s disease: a Chinese Real-world study
Thank you for the opportunity to review this interesting study. This is the first report on UST in
CD PK from Chinese, therefore the work is important added value. The strength of the work is
prospective observation and multiple endpoints analyzed. In particular, the endoscopy read by
experts adds robustness. The limitation of the study is its relatively limited sample size of 19
pts, but this could be appropriately addressed – please see my comments of Results section.
Specific comments:
CONLUSIONS: please replace “weapon” with for example “option” or “drug”.
INTRODUCTION: please focus more on what is known about PK in UST CD, you can easily
convert 1st paragraph to just one sentence to shorten this part.
RESULTS: since you excluded 18 pts due to follow-up less than 16 weeks please consider to wait
for this pts to reach week 16/20 and include also these. This would much increase the validity
of your results as you would almost double the cohort i.e 19 +18= 37 pts. You also excluded 17
pts due to lack of data (endoscopy, trough levels, colecotomy) – these pts should be included, as
you can still use their data to calculate the endpoints for which you have the data – for example
pts with colectomy should be regarded as “no endoscopic remission, no clinical remission…”.
In pts without trough levels you can still calculate clinical, endoscopic remission etc. By adding
these pts you could further increase the amount of pts 19+18+17=54 – this would again increase
the validity of your work. Furthermore, this would decrease the possible bias of your work.
DISCUSSION
Be careful about your conclusion that UST trough concentration of 1.12 is the optimal one.
In fact this is only correlation that you observe. I would guess the higher concentration the
better. But yes, I agree that pts with concentrations lower than this should be considered for dose
optimization as otherwise the chance of remission is low. Here you could also refer in discussion
to recent paper where ustekinumab concentrations after dose optimization predicted mucosal
healing, but not those before (Hanzel EJGH 2021, Ustekinumab concentrations shortly after
escalation to monthly dosing may identify endoscopic remission in refractory Crohn's disease)
Fugure 4: why do use cutoff of ustekinumab of 4.5 (and the one you identified 1.12?)
Review for 10.1186/s12876-021-01946-8 (2021)

Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 2 Date: 17 Sep 2021
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
Thank you for your modifications.
Review for 10.1186/s12876-021-01955-7 (2021)

Title: Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: A
diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle
aspiration
Version: 3 Date: 28 May 2021
Reviewer's report:
More details on technical procedures should be reported (for example which needle caliper,
suction, and so on....)
Although the title is quite generic, the manuscript is specifically focused on EUS-FNA.
Authors should change the title and discussion accordingly. Doing this, the following studies
should be cited and commented:
PMID: 32433914
- PMID: 31310744
- PMID: 29026598
I recommend the authors to have their manuscript revised by a native speaker for grammar and
clarity
Review for 10.1186/s12876-021-01955-7 (2021)

Title: Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: A
diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle
aspiration
Version: 3 Date: 28 Jun 2021
Reviewer's report:
The authors describe an interesting study looking at outcomes for patients with pancreatic cancer
who are considered suitable for resection. This is an interesting study but there are some issues
that need to be addressed:
1. More information is needed concerning the selection for EUS or not. It is the absolute crux
of this paper and is the single most important variable that may have caused bias. Explicit
description of selection criteria for EUS or not EUS needs to be given.
2. The accuracy of EUS-FNA here is very high. This usually occurs when centres combine
categories of results and exclude inadequate samples. The usual 5 categories are inadeqaute,
benign, atypia, suspicious but not definite for cancer and definite for cancer on cytology.
Could the authors please breakdown the results in this way to allow understanding of their
cytopathological results.
3. For the survival curves were these adjusted for other important variables such as chemo
therapy, R1/R0 etc as being in the FNA group or not would not be the only influencer of
outcomes.
4. Table 1 would be better to show the characteristics of both the EUS and non-EUS groups
with any statistical differences or not.
5. The discussion is very long and would benefit from being trimmed down significantly.
6. There are several spelling and grammatical errors throughout the manuscript e.g. "centers"
should be "centres", "tertial" should be "tertiary" and "viridity" should be "validity"
Review for 10.1186/s12876-021-01955-7 (2021)

Title: Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: A
diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle
aspiration
Version: 4 Date: 01 Sep 2021
Reviewer's report:
The manuscript is OK in the current form. Thank you!
Review for 10.1186/s12876-021-01976-2 (2021)

Title: Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in
patients with chronic constipation
Version: 0 Date: 24 Jul 2021
Reviewer's report:
This is a well written manuscript assessing an effectiveness and safety of the use of macrogol
4000 in addition to PEG before colonoscopy for patients with chronic constipation. This is the
first prospective study on the use of macrogol 4000 as a bowel-cleansing agent. Authors analyzed
a total of 40 patients and demonstrated clearly that the rate of good preparation is 92.5% (37/40)
and no adverse events were observed.
1. P8. line137. Tough authors described “All patients received a PEG dose of 1500 mL even if
the colonoscopy could be started when they had taken less than this amount.”, they described
“PEG taken, mL (range) = 1500 (1000-2000)” in Table 3. Were there patients who ingested only
1000ml of PEG in 40 cases? Please clarify it.
2. P12. line217. Not only constipation and diabetes but also inpatient status and tricyclic
antidepressant use are also known to be associated with inadequate bowel preparation. Please
clarify performance status and antidepressants use of the 40 cases, if possible.
3. P17. Line256. The authors described “A significantly greater proportion of patients rated the
tolerability of macrogol 4000 as good compared with PEG (95.0% vs. 50.0%, p < 0.01).”. The
amount of PEG is 1500ml, which is 6 times that of macrogol 4000. I think there is little meaning
to compare the tolerability of them.
4. ADR and PDR might be affected by previous colonoscopy and it`s bowel preparation. It will
be wonderful, if authors could report them of the 40 cases.
5. In this study, intake of macrogol 4000 in addition to PEG was effective and safe for
colonoscopy in patients with chronic constipation who could ingest 1500ml of PEG. Authors
should write about it in limitation section.
Review for 10.1186/s12876-021-01976-2 (2021)

Title: Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in
patients with chronic constipation
Version: 0 Date: 01 Aug 2021
Reviewer's report:
This study is a single-arm prospective study to investigate the efficacy and safety of macrogol
4000 intake the night before colonoscopy.
I think the main problem is the study design.
1. The main hypothesis of this study is to investigate the efficacy of the additional dose of
macrogol 4000 to PEG in patients with chronic constipation as bowel preparation. However,
single-arm trials are not generally used as confirmation of efficacy. There was no control group
for elucidating the efficacy of the macrogol 4000.
2. The ADR and PDR were remarkably higher than in other studies. Is there any selection bias
in the study?
3. Furthermore, in this study, macrogol 4000 is the additional dose to PEG. To compare the
tolerability of macrogol 4000 and PEG is not appropriate.
4. In figure 2, the BBPS was best at the transverse colon than the right-sided and left-sided colon.
The authors should describe some reasons for the results.
Review for 10.1186/s12876-021-01976-2 (2021)

Title: Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in
patients with chronic constipation
Version: 2 Date: 09 Oct 2021
Reviewer's report:
The authors responded sincerely to comments from our side. After revision, I thought that the
results were described well and discussion was appropriate.
Review for 10.1186/s12876-021-01959-3 (2021)

Title: Clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal
tract
Version: 1 Date: 27 Jul 2021
Reviewer:  Andrea Lisotti
Reviewer's report:
Dear Authors,
I have read with interest the enclosed manuscript dealing with endoscopic management of
foreign body ingestion in adult patients.
I found several issues that should be addressed in order to increase the overall quality of your
manuscript.
- The study included only adult (> 18-year-old) patients. I suggest to clearly state this choice
in the text and abstract.
- The introduction and discussion should refer to the most updated guidelines (ESGE and ASGE
at least)
- risk factors for adverse events included patients' age, foreign bodies' size and shape, and
impaction time. It is not clearly stated in the text if the authors tested also the location of foreign
body impaction (esophagus vs. stomach. vs. duodenum). I suggest to include this variable in the
univariate and multivariate analysis.
- I suggest assessing wheater airways intubation, overtube or transparent hood have a protective
role for adverse event.
- In the final paragraph of the conclusion, the Authors state "In addition, endoscopic procedures
in elderly patients and those with sharp foreign bodies may prevent adverse events." I failed to
understand if this sentence is supported by study results.
Review for 10.1186/s12876-021-01959-3 (2021)

Title: Clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal
tract
Version: 1 Date: 09 Aug 2021
Reviewer:  Arnaldo Amato
Reviewer's report:
This is a retrospective study aimed at investigating the clinical outcomes of endoscopic removal
of foreign bodies from the upper g-I tract and risk factors for adverse events.
The paper is clear, well written and easily readable. However, the topic is already present in
the literature and therefore the manuscript lacks originality. Among his strengths there are quite
large numbers, but unfortunately there is no really new contribution compared to what is already
known.
Moreover, some major and minor comments need to be made on the weaknesses of the study:
- considering the two involved centers, it would be interesting to know if there are differences in
accessibility to hospitals by patients or if there are substantial behavioral differences between the
population of the inland and of the coast, for example a different propensity to go to the hospital
- adverse events have been defined as evets requiring additional interventions.  However, in
the text they are divided into major and minor and accordingly reported and it’s reported that
most patients with AEs recovers without further intervention. So it’s not clear if this “further”
intervention refers to a repetition after a first intervention or to the first itself. Please write the
paragraph more clearly.
- Also in the discussion, starting on line 191, the sentence is not so clear, in detail it’s not clear
if “in this study” refers to the manuscript itself or to a previous cited study. Please rearranges
the sentence.
- It was reported that patients underwent TC-scan depending in clinical setting, can you describe
which were the indications and how many times the TC results changed the need for endoscopy
- Patients were not placed under conscious sedation, but additional protective measures were
occasionally used, patients with ingestion of foreign bodies are at higher risk of inhalation,
especially if they are small, during removal maneuvers. Why not carry out the procedure under
NORA? Moreover, it would be interesting to know when protective measures have been used
and whether there are hospital protocols for the management of foreign bodies and therefore
also for the use of such devices.
Review for 10.1186/s12876-021-01959-3 (2021)

Title: Clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal
tract
Version: 3 Date: 25 Sep 2021
Reviewer:  Andrea Lisotti
Reviewer's report:
Dear Authors
I have read with attention your revised version of the manuscript and I acknowledge that you
answered all questions raised during the peer review process.
The overall quality of the manuscript improved accordingly.
Review for 10.1186/s12876-021-01944-w (2021)

Title: Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing
primary curative resection
Version: 2 Date: 09 Apr 2021
Reviewer's report:
The study compares 168 patients selected over a 15 year time period. The improvements in
perioperative care would have affected the outcome and survival unless patients in specific time
cohorts were compared separately.
Review for 10.1186/s12876-021-01944-w (2021)

Title: Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing
primary curative resection
Version: 2 Date: 19 May 2021
Reviewer's report:
After carefully reviewing this manuscript, I have some questions and suggestions as following#
First, Was there only 168 patients diagnosed as non-B and non-C liver cancers from 2001 to
2016? If not, please describe in detail whether they did not undergo surgery or were lost to
follow-up. It is recommended that the exclusion criteria should include such patients.Second,
Did the patient receive treatment again after being discharged from the hospital, such as surgery
and drugs? Because these factors can affect the OS and DFS of patients. It is recommended
to describe information related to whether the patient has undergone other interventions after
discharge from the hospital.Third, It is recommended to describe why ALBI grades II and III
are combined together and whether this will affect the convincing power of ALBI grade as a
prognostic factor in patients with NBNC-HCC after primary curative resection.
Review for 10.1186/s12876-021-01944-w (2021)

Title: Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing
primary curative resection
Version: 4 Date: 07 Jun 2021
Reviewer's report:
This paper has been well revised for the prior problems, which may qualify for publication in
this journal. But there are still some new problems. Some comments are listed as follows:
1. In the result section of the text, the word description regarding exclusion criteria is repeated
with that of Figure 1.  These words had better be deleted .
2. The expression of numbers should be consistent in the paper. For example, the sentences,
“Sixty-six, 98, and 4 patients had ALBI grade I, II, and III, respectively”, “Fifty-eight patients
(34.5%) had diabetes mellitus (DM)” and so on should be further revised. In general, #10 is
expressed in English, while >10 is expressed in Arabic number.
Review for 10.1186/s12876-021-01957-5 (2021)

Title: A combined prediction model for biliary tract cancer using the prognostic nutritional index
and pathological findings: a single-center retrospective study
Version: 2 Date: 19 Jun 2021
Reviewer's report:
Authors explored the prognostic factors using a cohort of 117 patients with biliary tract cancer
who underwent surgical resection in their institution. They reported that prognostic nutritional
index, lymph node metastasis, and tumor differentiation remained independent prognostic
factors after multivariate analysis. In addition, they developed a combined prediction model
using these 3 independent prognostic factors.
This reviewer has several major concerns as follows.
1. The reproducibility of prediction models should be validated in an independent cohort. If
no independent cohort  is available, other methods such as bootstrapping could be applied to
validate its performance.
2. Is prognostic nutritional index superior to other established index such as NLR or GPS in
predicting prognosis in your cohort?
3. This was a retrospective study, but authors mentioned that  informed consent was obtained
from all individual participants.  It is unclear how authors obtained the informed consent from
the deceased patients.
Review for 10.1186/s12876-021-01957-5 (2021)

Title: A combined prediction model for biliary tract cancer using the prognostic nutritional index
and pathological findings: a single-center retrospective study
Version: 2 Date: 07 Jul 2021
Reviewer's report:
The authors analyzed 117 patients of resectable? biliary tract cancers and tried to identify
independent prognostic factors for overall survival and they described PNI, LN metastasis, and
tumor differentiation would be a prognostic factor and the formula of combined prediction model
were calculated. For publication quality, reviewer have some comments.
1. The authors investigated overall survival after surgical resection.  The observation period is
better to be over five years, or should be over three years. (Study period was from July 2010 to
March 2021.  The end of follow up was March 2021. The shortest period was 0 month.)
2. Please show recurrence free survival.  Because the chemotherapies after recurrence were
varied between 2010 and 2020.
3. The author did not compare the other nutrition/inflammation indices with PNI.  The author
should comment on superiority of PNI (reason for use of PNI).
4. Many study regarding PNI and BTC including meta-analysis were published.  Please show
the advantages of this manuscript compared with the previous reports.
5. Clavian-Dindo classification would be Roman numerals?
6. In table 2 and 3, primary disease and type of surgery should be included. (Only ICC
was included; the authors should show no connection between survival and primary disease
(perihilar, distal bile duct cancers, gall bladder cancers) )
7. Perioperative death would be excluded from the full analysis set.
8. Please the formula of combined prediction model at Figure 2 legend for easy identification of
the formula (in the current form, it was difficult to identify the formula).
9. No red line (count 0) in Figure 2b
Review for 10.1186/s12876-021-01957-5 (2021)

Title: A combined prediction model for biliary tract cancer using the prognostic nutritional index
and pathological findings: a single-center retrospective study
Version: 2 Date: 16 Jul 2021
Reviewer's report:
This paper describes the usefulness of PNI as a prognostic factor for biliary tract cancer. This
paper is well-written and I agree with the importance of PNI as a prognostic factor. However, I
have several comments for this paper to improve manuscript.
1. PNI reflects patients’ preoperative status because this score is calculated from preoperative
blood sample data. Therefore, several factors in Table 2 (peri-operative factors such as blood
loss, transfusion, postoperative complications, etc) may not be related to this score.
2. The grouping of biliary tract cancer include a large group of diverse cancer (intrahepatic
and extrhepatic cholangiocarcinoma, gallbladder cancer, ampullary cancer). These cancers are
reported to have different etiologies, different aggressive phenotypes and different therapeutic
responses. The analysis by sub-grouping of them should be provided.
3. How will the authors’ use PNI data for biliary cancer patients? Please discuss more
specifically.
Review for 10.1186/s12876-021-01966-4 (2021)

Title: Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing
advanced adenomatous polyps in Black patients
Version: 2 Date: 26 May 2021
Reviewer's report:
Thank you for the opportunity to review this manuscript on aspirin and statin mono or
dual chemoprophylaxis for prevention of advanced neoplasia. As the authors note, data on
chemoprevention is lacking in African Americans and work in this area is much needed. In
their paper, the authors review incidence of metachronous advanced neoplasia in an average risk
population and show that aspirin use, statin use, or both together did reduce advanced neoplasia
incidence compared to those who were not given any therapy. The paper is well-written.
I do have some major comments that should be addressed:
-Methods: I suspect that your group was rather heterogenous as your exclusion criteria was
limited to those with hereditary cancer syndromes and IBD. How about those with an advanced
lesion on baseline colonoscopy? Or having 8-9 polyps? Or 15 polyps but no referral for genetic
testing? Baseline colonoscopy groups should be stratified by risk status (e.g. those with a normal
colonoscopy, 1-2 polyps, or advanced lesions ,etc)
-Methods: Is data on sessile serrated lesions available? I recommend adding this.
-Medications: How was medication exposure determined? Data on length of use is important.
-Methods: it is unclear which colonoscopy was used as the index colonoscopy. And if an
individual had 5 colonoscopies, which was used for the surveillance interval – last colonoscopy?
First with a lesion?
-AAP arose in 19% of the cohort – this seems rather high for average risk colons. Please comment
on this.
-Methods: You astutely mention that comorbidities such as obesity and cardiovascular disease
are associated with increased risk for neoplasia. I recommend adjusting for some of these
variables as you have for BMI. The multivariate analysis could include Charleson Comorbidity
Index, or some of the factors utilized in metabolic syndrome, etc as an example.
Minor comments:
-How was poor bowel prep determined by endoscopy report – as in, which scales were used?
Review for 10.1186/s12876-021-01966-4 (2021)

Title: Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing
advanced adenomatous polyps in Black patients
Version: 2 Date: 28 Jun 2021
Reviewer:  Nagahide Matsubara
Reviewer's report:
The manuscript entitled “Short-term aspirin and statin chemoprophylaxis did not reduce the risk
of developing advanced adenomatous polyps in Black patients” by B.D. Renelus and others is
well prepared concerning the chemo-preventive effect of aspirin and statin on Black patients.
They conclude that short-term aspirin-statin did not reduce the risk of advanced adenomatous
polyps development in a cohort of Black patients. It is OK, but observation period is too short
to draw a conclusion.
People who took part in the early cardiovascular aspirin trials had fewer colorectal cancers 10
years later (Flossman et al. Lancet 2007). Meta-analysis of 8 vascular trials using aspirin revealed
fewer cancer deaths among those randomized to aspirin (Rothwell et al. Lancet 2011). When
you look at the prospective randomized trial data of aspirin on Lynch syndrome patients, it took
more than 10 years of follow up to reduce the incidence of colorectal cancer occurrence (HR
0.58) (Burn J etal. CaPP consortium Lancet 2011). More than that, this effect was only observed
with administration of high dose aspirin (600mg). According to the Women’s Health Study,
long term follow up reveals significant reduction in colorectal cancers after 10 years (Cook NR
et al. Annals of Internal medicine 2013;159:77-85).
Accordingly, this study is a little premature to draw a conclusion for aspirin to reduce the risk
of developing precursor lesion of colorectal cancer or even colorectal cancer. Observation of
additional 5 or more years may draw a definite different conclusion.
Review for 10.1186/s12876-021-01966-4 (2021)

Title: Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing
advanced adenomatous polyps in Black patients
Version: 4 Date: 12 Aug 2021
Reviewer's report:
Thank you for taking the time to review my recommendations and thoughtfully incorporating
the feedback.
There is one point that I feel should be addressed, which is the crux of the paper - medication
use. How long were those exposed to ASA and or statins exposed for? We are interested in those
who are long-term users. Though it is linked to the database, is there a way of excluding short
term users? (e.g. those who were on a statin for 1 month, or asa for 1 week). If not, this should
be added as a limitation, and any assumptions on length of use should be added to the methods.
Review for 10.1186/s12876-021-01962-8 (2021)

Title: Cyclin-Dependent Kinase 19 Upregulation Correlates with an Unfavorable Prognosis in
Hepatocellular Carcinoma
Version: 3 Date: 19 Jun 2021
Reviewer:  Weijia Liao
Reviewer's report:
The relationship between CDK19 and poor prognosis of HCC and the correlation between
CDK19 and biological function of HCC cells were analyzed by bioinformatics. The potential
value of CDK19 as a prognostic marker of HCC was confirmed in this paper, and basic cell
experiments were carried out for verification. There are still some parts that need to be modified.
1.The results of Fig 1C were obtained from the HPA database. It is suggested that the author
should use new collected clinical samples and add immunohistochemical experiments for
verification.
2.In the part of “Survival results and multivariate analysis in HCC”, How to determine the cut-
off value of high CDK19 group and low CDK19 group? How to group patients in this manuscript
needs to be described in detail, which is very important in the article. And why not use ROC
curve to determine the cut-off value of CDK19?
3.For Fig 3A, how to explain that the probability of patients with low CDK19 group was higher
than that of patients with high CDK19 group before 70 months, and the probability of patients
with low CDK19 group was higher than that of patients with CDK19 group after 100 months?
4.In the results part, authors used different patients databases for different analysis, please
describe the reasons for using different databases respectively in the text.
5.It is suggested that the sub-picture in Fig 5 be divided into two lines from one line.
6.In view of the discussion on the results of this study, it is suggested to increase the depth of
the discussion part.
Review for 10.1186/s12876-021-01962-8 (2021)

Title: Cyclin-Dependent Kinase 19 Upregulation Correlates with an Unfavorable Prognosis in
Hepatocellular Carcinoma
Version: 3 Date: 28 Jul 2021
Reviewer's report:
In this study, the authors gave a general introduction of a component of the Mediator co-activator
complex, cyclin-dependent kinase 19 (CDK19) and its prognostic value in hepatocellular
carcinoma (HCC). Although CDK19 may not have been investigated in HCC, CDK19 has been
studied in depth in several cancer types. In my opinion, therefore, this study lacks originality. In
the Discussion section, the author raised three scientific questions. Firstly, what is the potential
mechanism of CDK19 in HCC? Secondly, what mutations of CDK19 occur in HCC? Do
these mutations have a relationship with the prognosis? And finally, is CDK19 involved in the
pathological process of HCC through immune infiltration? These questions were not specific
and no hypothesis were provided to answer them, which makes it difficult to evaluate whether
the methods used in this study were appropriate.
There are also several issues in regard of the construction of the study and the article:
1. Although the language was overall comprehensible, there were typos, grammatical errors and
redundancies.
2. Proof read should be conducted as there were incomplete sentences in the article. For example,
line 331-332 “CDK19 is in a positive correlation with in immune infiltrates in.”
3. Fact check should be made to make sure that references were cited accurately. For example,
previous reports hardly indicated that Sorafenib is a molecular inhibitor of CDK19.
4. Methods described regarding the wet-bench experiments are questionable. For instance, for
the cell proliferation assay, the authors stated that 10000 cells were seeded per well in a 96#well
plate. This cell number is 10 times the amount compared to the most widely used protocol. It
would be difficult to get a reliable read with that many cells in a well.
5. SK-Hep-1 cell line is not recommended as it is a liver adenocarcinoma cell line.
Taken together, it is my opinion that there are fundamental issues in this study that cannot
be addressed. I therefore do not recommend further consideration for publication in BMC
Gastroenterology.
Review for 10.1186/s12876-021-01962-8 (2021)

Title: Cyclin-Dependent Kinase 19 Upregulation Correlates with an Unfavorable Prognosis in
Hepatocellular Carcinoma
Version: 4 Date: 24 Sep 2021
Reviewer:  Weijia Liao
Reviewer's report:
The author answered my questions and accepted my suggestion in the revised manuscript. There
is no further questions for me.
Review for 10.1186/s12876-021-01962-8 (2021)

Title: Cyclin-Dependent Kinase 19 Upregulation Correlates with an Unfavorable Prognosis in
Hepatocellular Carcinoma
Version: 4 Date: 05 Oct 2021
Reviewer's report:
In this study, the authors gave an introduction of a component of the Mediator co-activator
complex, cyclin-dependent kinase 19 (CDK19) and its prognostic value in hepatocellular
carcinoma (HCC). Furthermore, through database mining, the authors found that the expression
of CDK19 is associated with positive tumor immune infiltration, and due to its low gene mutation
rate, the authors suggested CDK19 may be used as an immune checkpoint in the future for HCC
treatment, which is worth further study in the future.
Review for 10.1186/s12876-021-01961-9 (2021)

Title: Perianal Disease Onset Age is Associated with Distinct Disease Features and Need for
Intestinal Resection in Perianal Crohn’s Disease: A Ten-year Hospital-based Observational
Study in China
Version: 2 Date: 10 May 2021
Reviewer's report:
Very honored author
Thank you very much for this interesting work.
The following questions arise:
- How was the delay defined in the diagnosis of PCD? Perianal symptoms do not mean that a
perianal fistula was already present at that time. Please specify exactly which starting point with
which symptoms was taken for this delay and how it could be defined retrospectively.
- What abdominal surgeries were performed? Are these comparable in both groups regarding
size and extensive of surgery (resections versus adhesiolysis etc.)?
- Clear definition of the primary endpoint and how or if this could be achieved.
- Is the need for abdominal surgery really age-associated and not also due to the other
comorbidities? A subgroup analysis with exclusion of smokers and others is certainly necessary.
- The group size of the two comparison groups is very different. Are these numbers really
comparable?
- Is there a correlation between the affected bowel segment and the severity of PCD?
Review for 10.1186/s12876-021-01939-7 (2021)

Title: Intriguing findings of liver fibrosis following Covid-19
Version: 1 Date: 10 Jun 2021
Reviewer's report:
This study tackles an important issue related to COVID-19 which assess liver fibrosis in
COVID-19 patients by serum HA and FIB-4 and to detect their relationship with liver function
tests, inflammatory markers, and blood oxygen saturation irrespective to underlying liver
disease.
My comments are.
1- In abstract section, there is a contradictory between P-value mentioned in sentence" HA
was higher in patients with higher liver stiffness (rs=0.30, p<0.05)" and in the sentence" SWE
correlated with HA (rs=0.30, p=0.021)". Please revise.
2- In introduction section, reference 5 [e.g. 5] ……….please omit "e.g".
3- In method section, the abbreviation of (RT-PCT) in the sentence "diagnosis of SARS-CoV-2
infection………."  Please correct to "RT-PCR".
4- Mention the unit of each parameter of FIB-4 equation.
5- In result section.
1- Author mentioned HA correlated with AST (rs=0.60, p<0.001) but r = 0.52 in the table 2
please revise.
2- Author mentioned HA correlated with FIB-4 (r=0.27) but r = 0.5 in the table 2 please revise.
3-  The sentence is not clear "HA correlated with all parameters but CRP". Please rephrase.
4- The sentence is not clear "Oxygen saturation at admission to the hospital was negatively
related with all of parameters but FIB-4". Please rephrase.
6- In Discussion section, reference 26 [e.g. 26] ……….please omit "e.g".
Review for 10.1186/s12876-021-01939-7 (2021)

Title: Intriguing findings of liver fibrosis following Covid-19
Version: 1 Date: 08 Jul 2021
Reviewer's report:
The authors investigated changes in liver fibrosis in COVID-19 patients, they assessed serum
hyaluronic acid and FIB-4   in 66 patients and 17 controls. They found that these markers may
be elevated  in more than half of patients in the study. I would like to thank the authors for this
great effort. However, l have major concerns:
- Sample size calculation and power of the study is important to validate the findings of the study.
- l also would like to ask why you selected 66 patients and 17 controls. Why this number and
not another number?
-In introduction, in the last sentence of the fourth paragraph, you stated that FIB-4 may not be
valid marker for fibrosis. SO, Why you selected FIB-4 for the study?
- In the third paragraph of methods, you mentioned that if the case has oxygen saturation below
93%, this will be considered respiratory failure. I ask you to revise this piece of information and
provide the reference for that.
Best regards
Review for 10.1186/s12876-021-01956-6 (2021)

Title: Comparison of the efficacy and safety between palliative biliary stent placement and duct
clearance among elderly patients with choledocholithiasis: A propensity score-matched analysis
Version: 1 Date: 31 Aug 2021
Reviewer's report:
The authors conducted a study to evaluate the usefulness of palliative endoscopic biliary stenting
in elderly patients with choledocholithiasis. The results showed that the median cholangitis-
free period was significantly shorter in the endoscopic biliary stenting group than in the
complete stone removal group; therefore, the authors concluded that palliative endoscopic
biliary stenting should be indicated only for patients with choledocholithiasis who have a poor
prognosis. This is an interesting and well-presented work. Readers will certainly benefit from
the study findings, which provide useful information on strategy development for frail elderly
patients with choledocholithiasis. However, I have few comments and questions regarding the
manuscript.
1. Although the results showed that there were no significant between-group differences
regarding any outcomes, except for cholangitis, the authors have not mentioned procedure time.
Notably, procedure time for biliary stenting is shorter than that for stone removal; therefore,
biliary stenting alone generally helps reduce adverse events in frail elderly patients with poor
general condition.
2. According to the results, cholangitis was mainly caused by stent migration in the endoscopic
biliary stenting group. In this group, straight plastic stents and pigtail stents were used in 68.0%
and 32.0% patients, respectively. Straight stents usually migrate in patients without biliary
stricture. Would it be possible to improve the outcomes in the biliary stenting group by using
pigtail stents in all patients? The authors should provide their opinion on this.