Reviewer’ s report
Title: Changes in Inflammatory Cytokines, Antioxidants and Liver Stiffness after Chelation
Therapy in Individuals with Chronic Lead Poisoning
Version: 0Date: 11 May 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
In this well-written and -executed original article, the authors performed two phased clinical studyinvestigating the effects of chelation therapy in patients with chronic lead poisoning. Phase onewas an analysis of a cross-sectional cohort composed of participants with severe chronic leadpoisoning. Phase two prospective interventional cohort that evaluated whether chelation therapycould reduce the lead-related liver injuries. Trial registration, ethical approval, and execution areplausible, and the primary outcomes clearly defined. The obvious setback of the present studyrelates to its design. Since no control group was included in this study, impact and conclusions arerather limited.
Nonetheless, the findings are intriguing and could attract a broad readership of hepatologists and
clinicians involved in pharmacology and toxicology. I, therefore, have only minor concerns asoutlined below.
REQUESTED REVISIONS:
The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whether
chelation therapy could reduce the lead-related liver injuries. The obvious setback of the present
study relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with[…].2.Following statement needs references: "Individuals with chronic lead poisoning, althoughuncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight of
patients?
ADDITIONAL REQUESTS/SUGGESTIONS:The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whetherchelation therapy could reduce the lead-related liver injuries. The obvious setback of the presentstudy relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with
[…].
2.Following statement needs references: "Individuals with chronic lead poisoning, although
uncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight ofpatients?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Reviewer’ s report
Title: Changes in Inflammatory Cytokines, Antioxidants and Liver Stiffness after Chelation
Therapy in Individuals with Chronic Lead Poisoning
Version: 0Date: 11 May 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
In this well-written and -executed original article, the authors performed two phased clinical studyinvestigating the effects of chelation therapy in patients with chronic lead poisoning. Phase onewas an analysis of a cross-sectional cohort composed of participants with severe chronic leadpoisoning. Phase two prospective interventional cohort that evaluated whether chelation therapycould reduce the lead-related liver injuries. Trial registration, ethical approval, and execution areplausible, and the primary outcomes clearly defined. The obvious setback of the present studyrelates to its design. Since no control group was included in this study, impact and conclusions arerather limited.
Nonetheless, the findings are intriguing and could attract a broad readership of hepatologists and
clinicians involved in pharmacology and toxicology. I, therefore, have only minor concerns asoutlined below.
REQUESTED REVISIONS:
The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whether
chelation therapy could reduce the lead-related liver injuries. The obvious setback of the present
study relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with[…].2.Following statement needs references: "Individuals with chronic lead poisoning, althoughuncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight of
patients?
ADDITIONAL REQUESTS/SUGGESTIONS:The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whetherchelation therapy could reduce the lead-related liver injuries. The obvious setback of the presentstudy relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with
[…].
2.Following statement needs references: "Individuals with chronic lead poisoning, although
uncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight ofpatients?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Please review this paper.
user
Reviewer’ s report
Title: Changes in Inflammatory Cytokines, Antioxidants and Liver Stiffness after Chelation
Therapy in Individuals with Chronic Lead Poisoning
Version: 0Date: 11 May 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
In this well-written and -executed original article, the authors performed two phased clinical studyinvestigating the effects of chelation therapy in patients with chronic lead poisoning. Phase onewas an analysis of a cross-sectional cohort composed of participants with severe chronic leadpoisoning. Phase two prospective interventional cohort that evaluated whether chelation therapycould reduce the lead-related liver injuries. Trial registration, ethical approval, and execution areplausible, and the primary outcomes clearly defined. The obvious setback of the present studyrelates to its design. Since no control group was included in this study, impact and conclusions arerather limited.
Nonetheless, the findings are intriguing and could attract a broad readership of hepatologists and
clinicians involved in pharmacology and toxicology. I, therefore, have only minor concerns asoutlined below.
REQUESTED REVISIONS:
The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whether
chelation therapy could reduce the lead-related liver injuries. The obvious setback of the present
study relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with[…].2.Following statement needs references: "Individuals with chronic lead poisoning, althoughuncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight of
patients?
ADDITIONAL REQUESTS/SUGGESTIONS:The authors can be congratulated to this well-executed clinical study. The authors performed twophased clinical study investigating the effects of chelation therapy in patients with chronic leadpoisoning. Phase one was an analysis of a cross-sectional cohort composed of participants withsevere chronic lead poisoning. Phase two prospective interventional cohort that evaluated whetherchelation therapy could reduce the lead-related liver injuries. The obvious setback of the presentstudy relates to its design. Since no control group was included in this study, impact andconclusions on efficacy of chelation therapy upon chronic lead poisoning are rather limited. Theauthors should clearly state this in the introduction.
Minor concerns:
1.This is not a randomized controlled trial. Therefore, the authors are unable to analyze cause andeffect, and erroneous conclusions drawn from the present study should be avoided. Severalstatements within the discussion and conclusions should be re-phrased, since they areoverreaching. For example: "Treatment by chelation decreases inflammation and replenishesantioxidants, and potentially reduces the degree of LS." Better: Treatment […] was associated with
[…].
2.Following statement needs references: "Individuals with chronic lead poisoning, although
uncommon, have non-specific symptoms such as constipation, anorexia and recurrent colickyabdominal pain that have an insidious onset and affect multiple organ systems."3.Could the authors explain their rather unusual dosing scheme during phase two (invention part).Is this in line with national guidelines? Was the dosage not adjusted to the body weight ofpatients?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within aspecified timeframe. Honoraria for reviews such as this are paid regardless of the reviewerrecommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
assistant