Title: A novel inflammatory marker for extensive ulcerative colitis; Endocan
Version: 3 Date: 31 Oct 2022
Reviewer's report:
• The language used throughout the paper could be refined. Please find examples below.
a) “usability” might be replaced with “utility”
b) “there is not enough data in the literature”- please rephrase
c) “mayo endoscopic score” should be “Mayo endoscopic score”
d) “beyond the splenic flexure to the proximal was classified as pancolitis”-- "beyond the splenic
flexure proximally "
e) “Receiver Operating Characteristic (ROC) Analysis and Youden Index; It was were used to
determine the sensitivity…”- please review grammar
f) “According to the ROC analysis;  The endocan……”
g) DISCUSSION….no accents on I in disucssion
h) “associated with higher risks for complications…”- needs to be re-phrased. Higher risk than
what?
• Need to explain what Endocan is early in the abstract. The authors give a very brief synopsis of
endocan in the introduction. The reader would benefit from additional background information.
• Is endocan affected by liver and renal disease? Will this affect its broader application and
interpretation?
• Methods:
• Who performed the endoscopic evaluation? Was there any form of central reading or
assessment of inter-observer variation?
• Results:
• The legends for the figures should contain enough relevant information to allow them to be
interpreted without reading the paper.
• Discussion:
• “It has been stated in studies that more research is needed to measure the extent of inflammatory
bowel disease at the appropriate time and to evaluate its effectiveness with one-on-one trials.”-
please cite relevant studies
• Authors that this is a preliminary study to detect severity and extent…. Have you shown
endocan reflects disease severity based on MES? Does disease extent alone in UC determine
our treatment decisions?
• “Considering that the endocan level is high in patients with IBD, the fact that this elevation
mostly indicates patients with common colitis adds value to our study.”- please clarify this
statement, what is meant by common colitis? Are there studies to demonstrate endocan levels
are not elevated in small bowel Crohn’s disease? Statement is also duplicated.
• “As the prevalence and severity of ulcerative colitis increase, inflammatory markers in serum
and stool increase.”- prevalence doesn’t have a bearing on inflammatory markers
• “Colonoscopy should be performed every 1-5 years to track the flare-ups.”- what is meant by
tracking flare-ups? Do the authors mean that colonoscopy is used to assess endoscopic response
to therapy or to investigate disease flares?
• “not an appropriate procedure for monitoring the disease.”- this is a broad statement open
to criticism, bearing in mind that endoscopic remission is the goal of therapy in UC based on
STRIDE II guidelines.  Colonoscopy certainly plays a role in disease monitoring, perhaps the
authors mean that colonoscopy should be used judiciously in disease monitoring, when it will
influence therapeutic decisions.
• “and to decide on hospitalization for severe disease”- important to impart on the reader
that calprotectin levels or CRP alone are not the criteria used to decide if a patient requires
hospitalization. Please rephrase this.
Fundamental questions that the authors need to address:
1. How is endocan a better serum inflammatory marker than CRP? The data supporting its
diagnostic value in disease extent is not very strong.
2. Is endocan specific to the gut? The authors quote numerous papers from rheumatology and
pancreatic literature. It appears endocan is elevated across a broad spectrum of inflammatory
conditions. The authors need to put forth a stronger argument with supporting data as to why we
should use endocan instead of calprotectin which is gut specific.
Title: A novel inflammatory marker for extensive ulcerative colitis; Endocan
Version: 3 Date: 31 Oct 2022
Reviewer's report:
• The language used throughout the paper could be refined. Please find examples below.
a) “usability” might be replaced with “utility”
b) “there is not enough data in the literature”- please rephrase
c) “mayo endoscopic score” should be “Mayo endoscopic score”
d) “beyond the splenic flexure to the proximal was classified as pancolitis”-- "beyond the splenic
flexure proximally "
e) “Receiver Operating Characteristic (ROC) Analysis and Youden Index; It was were used to
determine the sensitivity…”- please review grammar
f) “According to the ROC analysis;  The endocan……”
g) DISCUSSION….no accents on I in disucssion
h) “associated with higher risks for complications…”- needs to be re-phrased. Higher risk than
what?
• Need to explain what Endocan is early in the abstract. The authors give a very brief synopsis of
endocan in the introduction. The reader would benefit from additional background information.
• Is endocan affected by liver and renal disease? Will this affect its broader application and
interpretation?
• Methods:
• Who performed the endoscopic evaluation? Was there any form of central reading or
assessment of inter-observer variation?
• Results:
• The legends for the figures should contain enough relevant information to allow them to be
interpreted without reading the paper.
• Discussion:
• “It has been stated in studies that more research is needed to measure the extent of inflammatory
bowel disease at the appropriate time and to evaluate its effectiveness with one-on-one trials.”-
please cite relevant studies
• Authors that this is a preliminary study to detect severity and extent…. Have you shown
endocan reflects disease severity based on MES? Does disease extent alone in UC determine
our treatment decisions?
• “Considering that the endocan level is high in patients with IBD, the fact that this elevation
mostly indicates patients with common colitis adds value to our study.”- please clarify this
statement, what is meant by common colitis? Are there studies to demonstrate endocan levels
are not elevated in small bowel Crohn’s disease? Statement is also duplicated.
• “As the prevalence and severity of ulcerative colitis increase, inflammatory markers in serum
and stool increase.”- prevalence doesn’t have a bearing on inflammatory markers
• “Colonoscopy should be performed every 1-5 years to track the flare-ups.”- what is meant by
tracking flare-ups? Do the authors mean that colonoscopy is used to assess endoscopic response
to therapy or to investigate disease flares?
• “not an appropriate procedure for monitoring the disease.”- this is a broad statement open
to criticism, bearing in mind that endoscopic remission is the goal of therapy in UC based on
STRIDE II guidelines.  Colonoscopy certainly plays a role in disease monitoring, perhaps the
authors mean that colonoscopy should be used judiciously in disease monitoring, when it will
influence therapeutic decisions.
• “and to decide on hospitalization for severe disease”- important to impart on the reader
that calprotectin levels or CRP alone are not the criteria used to decide if a patient requires
hospitalization. Please rephrase this.
Fundamental questions that the authors need to address:
1. How is endocan a better serum inflammatory marker than CRP? The data supporting its
diagnostic value in disease extent is not very strong.
2. Is endocan specific to the gut? The authors quote numerous papers from rheumatology and
pancreatic literature. It appears endocan is elevated across a broad spectrum of inflammatory
conditions. The authors need to put forth a stronger argument with supporting data as to why we
should use endocan instead of calprotectin which is gut specific.
Please review this paper.
user
Title: A novel inflammatory marker for extensive ulcerative colitis; Endocan
Version: 3 Date: 31 Oct 2022
Reviewer's report:
• The language used throughout the paper could be refined. Please find examples below.
a) “usability” might be replaced with “utility”
b) “there is not enough data in the literature”- please rephrase
c) “mayo endoscopic score” should be “Mayo endoscopic score”
d) “beyond the splenic flexure to the proximal was classified as pancolitis”-- "beyond the splenic
flexure proximally "
e) “Receiver Operating Characteristic (ROC) Analysis and Youden Index; It was were used to
determine the sensitivity…”- please review grammar
f) “According to the ROC analysis;  The endocan……”
g) DISCUSSION….no accents on I in disucssion
h) “associated with higher risks for complications…”- needs to be re-phrased. Higher risk than
what?
• Need to explain what Endocan is early in the abstract. The authors give a very brief synopsis of
endocan in the introduction. The reader would benefit from additional background information.
• Is endocan affected by liver and renal disease? Will this affect its broader application and
interpretation?
• Methods:
• Who performed the endoscopic evaluation? Was there any form of central reading or
assessment of inter-observer variation?
• Results:
• The legends for the figures should contain enough relevant information to allow them to be
interpreted without reading the paper.
• Discussion:
• “It has been stated in studies that more research is needed to measure the extent of inflammatory
bowel disease at the appropriate time and to evaluate its effectiveness with one-on-one trials.”-
please cite relevant studies
• Authors that this is a preliminary study to detect severity and extent…. Have you shown
endocan reflects disease severity based on MES? Does disease extent alone in UC determine
our treatment decisions?
• “Considering that the endocan level is high in patients with IBD, the fact that this elevation
mostly indicates patients with common colitis adds value to our study.”- please clarify this
statement, what is meant by common colitis? Are there studies to demonstrate endocan levels
are not elevated in small bowel Crohn’s disease? Statement is also duplicated.
• “As the prevalence and severity of ulcerative colitis increase, inflammatory markers in serum
and stool increase.”- prevalence doesn’t have a bearing on inflammatory markers
• “Colonoscopy should be performed every 1-5 years to track the flare-ups.”- what is meant by
tracking flare-ups? Do the authors mean that colonoscopy is used to assess endoscopic response
to therapy or to investigate disease flares?
• “not an appropriate procedure for monitoring the disease.”- this is a broad statement open
to criticism, bearing in mind that endoscopic remission is the goal of therapy in UC based on
STRIDE II guidelines.  Colonoscopy certainly plays a role in disease monitoring, perhaps the
authors mean that colonoscopy should be used judiciously in disease monitoring, when it will
influence therapeutic decisions.
• “and to decide on hospitalization for severe disease”- important to impart on the reader
that calprotectin levels or CRP alone are not the criteria used to decide if a patient requires
hospitalization. Please rephrase this.
Fundamental questions that the authors need to address:
1. How is endocan a better serum inflammatory marker than CRP? The data supporting its
diagnostic value in disease extent is not very strong.
2. Is endocan specific to the gut? The authors quote numerous papers from rheumatology and
pancreatic literature. It appears endocan is elevated across a broad spectrum of inflammatory
conditions. The authors need to put forth a stronger argument with supporting data as to why we
should use endocan instead of calprotectin which is gut specific.
assistant