Rigor Reviewed

Rigor-Reviewed Manuscript

Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)

Name: Adcurare Rigor Record — Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)
Item: Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)
Rating: 92
Author: Adcurare

Attar A, Mirhosseini SA, Mathur A, Dowlut S, Monabati A, Kasaei M, Abtahi F, Kiwan Y, Vosough M, Azarpira N.

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Adcurare Rigor Review — 2.5★ (Weak), 0 critical, 12 high issues for “Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 6, 2026

Adcurare Rigor Review

Rigor Reviewed

2.5 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★
ReportingKey resources not met−0.5★

Model-reported confidence: highReviewer agreement: moderateEngine: 7.6.0Source: full text

Problems surfaced3 types

Key resources not identified
Implausibly large reported effect
Internal contradictions in the reported numbers

This Adcurare Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper presents a well-designed phase 3 RCT with strong reporting transparency and data availability. However, several rigor gaps need attention: the power analysis lacks explicit alpha and power, key resources (antibodies, cell product identifier, mycoplasma testing) are incompletely reported, biological variable reporting is incomplete (sex justification, race/ethnicity), and a minor statistical discrepancy exists in Table 2.

Three independent reviewers evaluated all eight dimensions; their ratings diverged on study design, biological variables, key resources, and statistical analysis, with the synthesized statuses reflecting the more specific and verifiable evidence. The statistics verification component checked 16 tests and found all consistent, but coverage is limited to tests with a test statistic and df or an effect estimate with CI.

12 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 16 tests: 16 consistent, 0 inconsistent, 16 via agent-written checks.

4 integrity concerns flagged (0 high).

Reporting

Eight Dimensions7 pass · 1 fail

Prior work is cited, including the BAMI trial and meta-analyses, with acknowledgment of limitations such as small samples and surrogate endpoints. The rationale linking these gaps to the current study's objectives is clear. Limitations of prior research (e.g., short follow-up, focus on surrogate endpoints) are directly addressed by the study design (e.g., larger sample, clinical endpoint, longer follow-up).

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific premise by citing prior work on stem cell therapy limitations, and provides a logical rationale for using MSCs and a clinical endpoint.

Evidence

direct quote[Introduction, paragraphs 1-4]

“Most clinical trials investigating stem cell therapy have been limited by small sample sizes and a focus on surrogate endpoints... The BAMI trial... did not show a significant benefit.”

direct quote[Introduction, paragraph 4]

“Building on these insights, we designed a phase 3 clinical trial with long term follow-up to assess the effect of intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells on the development of post-myocardial infarction heart failure.”

paraphrase[Introduction, paragraphs 1-4 and Discussion, 'Strengths and limitations of study']

“The study addresses limitations of small samples, surrogate endpoints, and short follow-up by using a large sample, clinical primary endpoint, and a three-year follow-up.”

PASSReviewer 2· 95% conf

The paper establishes a clear scientific foundation by citing relevant prior work, providing a logical rationale, and addressing limitations of previous studies.

Evidence

direct quote[Introduction, paragraph 3]

“The BAMI trial, the largest phase 3 trial in this area, used total mortality as its primary endpoint but did not show a significant benefit, despite a significant reduction in hospital admissions for heart failure after intracoronary infusion of bone marrow derived mononuclear cells. These findings highlight the challenges of using mortality as a primary endpoint in cell therapy trials and suggest that incidence of heart failure may be a more appropriate and sensitive clinical outcome for evaluating efficacy.”

direct quote[Introduction, final paragraph]

“Our previous phase 2 trial showed the effectiveness of intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells in improving left ventricular ejection fraction after myocardial infarction. Building on these insights, we designed a phase 3 clinical trial with long term follow-up to assess the effect of intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells on the development of post-myocardial infarction heart failure.”

direct quote[Discussion, 'Strengths and limitations of study']

“This study, by using mesenchymal stem cells instead of bone marrow derived mononuclear cells, enrolling a selected at risk population of patients, having a long term follow-up, enrolling the largest sample size in the field, and using a clinical endpoint instead of surrogate endpoints such as left ventricular ejection fraction, may have paved a new way in the field of regenerative cardiology.”

PASSReviewer 3· 95% conf

The paper establishes a clear scientific premise by citing prior work on post-MI heart failure, stem cell therapy, and the limitations of previous trials, and provides a logical rationale for the study.

Evidence

direct quote[Introduction, paragraph 1-3]

“Despite growing interest, most clinical trials investigating stem cell therapy have been limited by small sample sizes and a focus on surrogate endpoints such as cardiac biomarkers, left ventricular ejection fraction, or scar size.”

direct quote[Introduction, paragraph 3]

direct quote[Introduction, paragraph 4]

“Building on these insights, we designed a phase 3 clinical trial with long term follow-up to assess the effect of intracoronary infusion of Wharton's jelly derived mesenchymal stem cells on the development of post-myocardial infarction heart failure.”

Randomization used permuted block randomization via a web-based system. Blinding is single-blind with a rationale (sham not permitted), and outcome assessors were blinded. Inclusion/exclusion criteria are clearly defined. The analysis population and handling of missing data are described. The sample size calculation mentions assumed rates and dropout but does not explicitly state the significance level (alpha) or desired power, making it reported_but_inadequate. No other applicable sub-criteria are missing.

Sub-criteria

controlsN/A

power analysisINADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study design is generally rigorous, with adequate randomization, blinding of outcome assessors, and pre-specified inclusion/exclusion criteria, but the power analysis lacks explicit alpha and power values.

Evidence

direct quote[Methods, 'Sample size, randomisation, and blinding']

“Randomisation was done centrally at the main study centre by using permuted block randomisation (block size of six), implemented through a web based randomisation system”

direct quote[Methods, 'Sample size, randomisation, and blinding']

“However, all researchers, clinicians, and staff members responsible for follow-up care, outcome adjudication, and data analysis remained blinded.”

direct quote[Methods, 'Sample size, randomisation, and blinding']

“To ensure adequate statistical power to enable adjustment for at least three to five covariates, we needed a minimum of 30-40 heart failure events in the total population.”

WARNReviewer 2· 90% conf

The study design is generally rigorous with central randomization, single blinding, a pre-specified analysis population, and a sample size calculation, but the absence of a sham procedure (single blinding), lack of a power analysis for the primary endpoint based on own data, and absence of detailed outlier handling criteria yield a warn.

Evidence

direct quote[Methods, 'Sample size, randomisation, and blinding']

“Randomisation was done centrally at the main study centre by using permuted block randomisation (block size of six), implemented through a web based randomisation system (https://www.sealedenvelope.com/randomisation/simulation/).”

direct quote[Methods, 'Sample size, randomisation, and blinding']

“Ethics committee and institutional review board restrictions meant that a sham procedure was not permitted and patients could not be blinded to allocation. However, all researchers, clinicians, and staff members responsible for follow-up care, outcome adjudication, and data analysis remained blinded.”

paraphrase[Methods, 'Sample size, randomisation, and blinding']

“The sample size was calculated based on heart failure incidence rates from the BAMI trial (3.9% in intervention, 12% in control) to ensure 30-40 events, then increased to 420 to account for 8-10% dropout. This does not represent a standard a priori power analysis with a prespecified effect size, alpha, and power.”

PASSReviewer 3· 90% conf

The study design is rigorous for a phase 3 RCT, with adequate reporting of randomization, blinding, sample size calculation, and inclusion/exclusion criteria. Some elements like outlier handling and independent replication are not applicable for this type of trial.

Evidence

direct quote[Methods, Sample size, randomisation, and blinding]

“Randomisation was done centrally at the main study centre by using permuted block randomisation (block size of six), implemented through a web based randomisation system ( https://www.sealedenvelope.com/randomisation/simulation/ ).”

direct quote[Methods, Sample size, randomisation, and blinding]

“We initially calculated the sample size to include approximately 118 patients in the intervention arm and 220 patients in the control arm to detect a difference in heart failure incidence rate, assuming rates of 3.9% in the intervention group and 12% in the control group on the basis of the results from the BAMI trial.”

Sex is reported (85% male in intervention, 79% male in control). Age, weight (BMI), health status, and demographics (smoking, comorbidities, etc.) are presented in Table 1. Both sexes were included, so a single-sex justification is not applicable. All applicable sub-criteria are adequately reported.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Biological variables including sex, age, weight/health, and demographics are well reported with adequate detail.

Evidence

direct quote[Results, Table 1]

“Male sex | 115 (85) | 205 (79) | 320 (81)”

direct quote[Results, Table 1]

“Mean (SD) age, years | 57.8 (10.7) | 59.2 (10.9) | 58.7 (10.8)”

WARNReviewer 2· 85% conf

The paper reports some biological variables but lacks justification for single-sex study (85% male in intervention group) and does not report age as a continuous variable with full distributional details or other demographics like race/ethnicity.

Evidence

direct quote[Table 1]

“Male sex: 115 (85%) in intervention, 205 (79%) in control.”

direct quote[Table 1]

“Mean (SD) age, years: 57.8 (10.7) in intervention, 59.2 (10.9) in control.”

absence[Table 1]

Race/ethnicity is not reported, and weight/BMI data are incomplete.

PASSReviewer 3· 95% conf

The paper adequately reports key biological variables for a human clinical trial, including sex, age, and a comprehensive set of demographic and clinical characteristics.

Evidence

direct quote[Table 1]

“Male sex | 115 (85) | 205 (79) | 320 (81)”

direct quote[Table 1]

“Mean (SD) age, years | 57.8 (10.7) | 59.2 (10.9) | 58.7 (10.8)”

paraphrase[Table 1]

“Table 1 includes demographics, signs at admission, medical history, laboratory findings, echocardiographic findings, and hospital administered drugs.”

The study protocol was approved by the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409). Informed consent was obtained from all patients, and the consent process adhered to the Declaration of Helsinki. Regulatory compliance with the Declaration of Helsinki is stated.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval from a named IRB with protocol number, informed consent, and regulatory compliance are all adequately reported.

Evidence

direct quote[Ethics statements]

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409)”

direct quote[Ethics statements]

“All patients gave informed consent.”

direct quote[Ethics statements]

“The trial adhered to the principles outlined in the Declaration of Helsinki.”

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported: a named ethics committee approved the study with a protocol number, informed consent was obtained, and regulatory compliance (Declaration of Helsinki) is stated.

Evidence

direct quote[Methods, 'Ethics statements']

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409) and is registered on ClinicalTrials.gov with the identifier NCT05043610.”

direct quote[Methods, 'Consent']

“All patients gave informed consent.”

direct quote[Methods, 'Consent']

“The consent process was conducted in accordance with the Declaration of Helsinki, upholding the principles of autonomy and respect for persons.”

PASSReviewer 3· 95% conf

The paper provides a clear ethics approval statement with a named committee and protocol number, describes informed consent, and states compliance with the Declaration of Helsinki.

Evidence

direct quote[Ethics statements]

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409)”

direct quote[Methods, Consent]

“All patients gave informed consent.”

direct quote[Abstract]

“Trial registration ClinicalTrials.gov NCT05043610 .”

Flow cytometry antibodies for cell characterization (CD105, CD73, etc.) are mentioned without vendor/catalog numbers/RRID (reported_but_inadequate). Mycoplasma testing is not explicitly reported (not_reported). The investigational cell product (Wharton's jelly MSCs) is described in detail but lacks a unique identifier such as a cell bank catalog number or RRID (reported_but_inadequate). Stata version 18 is adequately reported (reported_and_adequate). With 1 of 4 applicable sub-criteria adequate, the dimension fails.

Sub-criteria

mycoplasma testingNOT REPORTED

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedINADEQUATE

cell line authenticationINADEQUATE

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 70% conf

Critical resources such as antibodies used for flow cytometry and mycoplasma testing are not adequately identified or reported; the cell product lacks a standard identifier, and only the statistical software is adequately identified.

Evidence

direct quote[Methods, 'Intracoronary infusion of mesenchymal stem cells']

“flow cytometry analysis showed the expression of surface markers CD105, CD73, and CD90, whereas the cells were negative for CD45, CD34, CD11b, CD31, and HLA-DR”

absence[Methods, 'Intracoronary infusion of mesenchymal stem cells']

Mycoplasma testing is not explicitly reported.

direct quote[Methods, 'Intracoronary infusion of mesenchymal stem cells']

“allogenic human Wharton’s jelly derived mesenchymal stem cells”

WARNReviewer 2· 90% conf

The investigational product (mesenchymal stem cells) is identified with source and characterization, but key details like lot numbers, specific product/manufacturer name for the stem cell product, and software version are missing.

Evidence

paraphrase[Methods, 'Intracoronary infusion of mesenchymal stem cells']

“The cells are described as Wharton's jelly derived mesenchymal stem cells, characterized by surface markers and differentiation ability, but no lot number, commercial product name, or specific manufacturer is given.”

direct quote[Methods, 'Statistical analysis']

“We used Stata version 18 for all statistical analysis.”

direct quote[Methods, 'Intracoronary infusion of mesenchymal stem cells']

“flow cytometry analysis showed the expression of surface markers CD105, CD73, and CD90, whereas the cells were negative for CD45, CD34, CD11b, CD31, and HLA-DR, aligning with ISCT standards.”

PASSReviewer 3· 90% conf

The investigational product (Wharton's jelly derived mesenchymal stem cells) is adequately identified with source, preparation, and quality control details. Statistical software is identified.

Evidence

direct quote[Methods, Intracoronary infusion of mesenchymal stem cells]

“The mesenchymal stem cells used in our study were sourced from Wharton's jelly derived mesenchymal stem cells. The umbilical cords used for isolation of Wharton's jelly derived mesenchymal stem cells came from full term births of baby boys.”

direct quote[Methods, Intracoronary infusion of mesenchymal stem cells]

“We adhered to the minimal criteria established by the International Society for Cell and Gene Therapy (ISCT) to characterise mesenchymal stem cells.”

direct quote[Methods, Statistical analysis]

“We used Stata version 18 for all statistical analysis.”

The paper names all statistical tests used (e.g., independent sample Student's t test, Mann-Whitney U test, χ2 test, Fisher's exact test, Kaplan-Meier, log-rank test, Cox proportional hazards regression, Wilcoxon matched pairs signed rank test, linear regression). Exact p-values are reported for primary and secondary endpoints (e.g., P=0.024, P=0.015). Effect sizes (hazard ratios) and 95% confidence intervals are provided. Statistical software (Stata version 18) is identified. Data presentation includes Kaplan-Meier curves, tables with event rates and person-years, and a box plot for LVEF. Assumptions for Cox regression (proportional hazards) were tested using Schoenfeld residuals. The paper does not explicitly verify normality assumptions for all tests, but this is less critical for a large clinical trial using standard methods.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Most statistical reporting is adequate, including named tests, assumption checks, exact p-values, effect sizes with CIs, and software identification, but a minor discrepancy in the annual incidence rate calculation in Table 2 suggests possible rounding or typo, which is noted but does not affect the overall pass.

Evidence

direct quote[Methods, 'Statistical analysis']

“We used the Kruskal-Wallis and Shapiro-Wilk normality tests to assess the normality of continuous variables.”

direct quote[Results, 'Endpoint analysis' and Figure 3]

“crude hazard ratio 0.43, 95% CI 0.21 to 0.89; P=0.024”

direct quote[Methods, 'Statistical analysis']

“We used Stata version 18 for all statistical analysis.”

WARNReviewer 2· 85% conf

Statistical analysis is thorough with named tests and adjustments, but the assumption verification is inadequate for a small-to-moderate sample trial, exact p-values are not consistently reported (some use thresholds), and no effect sizes with confidence intervals are reported for some comparisons.

Evidence

direct quote[Methods, 'Statistical analysis']

“We used the Kruskal-Wallis and Shapiro-Wilk normality tests to assess the normality of continuous variables.”

direct quote[Results, 'Endpoint analysis']

“Cox regression analysis showed that intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells had a protective effect against development of heart failure (crude hazard ratio 0.43, 95% CI 0.21 to 0.89) and readmission to hospital for heart failure (0.22, 0.06 to 0.74).”

direct quote[Results, 'Endpoint analysis']

“Kaplan-Meier survival estimates for the primary endpoint showed a statistically significant reduction in incidence of heart failure and readmission to hospital for heart failure in the intervention group compared with the control group (log-rank test, P=0.020 and 0.007, respectively).”

PASSReviewer 3· 90% conf

The statistical analysis is well-described, with named tests, exact p-values, effect sizes with confidence intervals, and software identified. Data presentation includes Kaplan-Meier curves and tables with event rates.

Evidence

direct quote[Methods, Statistical analysis]

“We used Cox proportional hazards regression models to compare primary and secondary endpoints between study groups, adjusting for covariates.”

direct quote[Abstract, Results]

“Intracoronary infusion of mesenchymal stem cells had a preventive effect for incidence of heart failure (2.77 v 6.48 per 100 person years; hazard ratio 0.43, 95% confidence interval 0.21 to 0.89; P=0.024)”

direct quote[Methods, Statistical analysis]

“Furthermore, we evaluated the proportional hazards assumption by using the global test on the basis of scaled Schoenfeld residuals, with results reported in the supplementary materials.”

A data availability statement is present and links to the Figshare repository with a DOI (10.6084/m9.figshare.29375153.v2). No accession numbers are needed (no sequencing data). Code sharing is not applicable because all analyses used commercial Stata software with no custom code. Both applicable sub-criteria are adequate.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

De-identified individual participant data are deposited in Figshare with a DOI, and code sharing is not applicable as no custom code was used.

Evidence

direct quote[Data availability statement]

“De-identified individual participant data underlying the results reported in this article are available through the Figshare sharing platform ( https://doi.org/10.6084/m9.figshare.29375153.v2 )”

PASSReviewer 2· 90% conf

Data availability is adequately reported: a data availability statement names a repository (Figshare) with a DOI, providing concrete access. Code sharing is not applicable as no bespoke code is mentioned.

Evidence

direct quote[Methods, 'Data availability statement']

“De-identified individual participant data underlying the results reported in this article are available through the Figshare sharing platform (https://doi.org/10.6084/m9.figshare.29375153.v2).”

PASSReviewer 3· 95% conf

The paper provides a data availability statement with a concrete route to access de-identified individual participant data via a public repository with a DOI.

Evidence

direct quote[Data availability statement]

“De-identified individual participant data underlying the results reported in this article are available through the Figshare sharing platform ( https://doi.org/10.6084/m9.figshare.29375153.v2 ).”

Methods are comprehensive. Trial registration is provided (NCT05043610). CONSORT adherence is stated. All pre-specified primary and secondary outcomes are reported, including null results. Limitations are discussed (sham not possible, small events, confounders). Conclusions are proportional to the evidence. Funding sources and grant numbers are listed, and a COI statement is included.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The manuscript adheres to CONSORT, is registered, reports all outcomes, discusses limitations, and provides funding and COI statements.

Evidence

direct quote[Abstract and Ethics statements]

“Trial registration ClinicalTrials.gov NCT05043610”

direct quote[Methods]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

direct quote[Discussion, 'Strengths and limitations of study']

“The limitations of this study include the inability to do a sham procedure for the control group...”

PASSReviewer 2· 90% conf

Reporting is transparent: methods are detailed, the trial is registered, CONSORT guidelines are referenced, results are reported for all outcomes, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Methods, 'Ethics statements']

direct quote[Methods]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

direct quote[Discussion, 'Strengths and limitations of study']

“The limitations of this study include the inability to do a sham procedure for the control group, which would have allowed for a double blinded study design instead of a single blinded format. We did not assess heart failure biomarkers or investigate the physiological effects of the intervention on cardiac tissue...”

PASSReviewer 3· 90% conf

The paper demonstrates high reporting transparency with a trial registration number, adherence to CONSORT guidelines, a discussion of limitations, proportional conclusions, and a funding/COI statement.

Evidence

direct quote[Abstract]

“Trial registration ClinicalTrials.gov NCT05043610 .”

direct quote[Methods]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

direct quote[Discussion, Strengths and limitations of study]

“The limitations of this study include the inability to do a sham procedure for the control group, which would have allowed for a double blinded study design instead of a single blinded format.”

16 copyedit issues flagged: mostly typo, consistency, punctuation.

Checked 36 references: 36 verified.

Reproducibility

4 data/code links checked; 4 live.

Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after minor-to-moderate edits. The most consequential gaps are in key resources (missing identifiers and mycoplasma testing) and the statistical discrepancy in Table 2. Addressing these, along with the copyedit fixes, will bring the manuscript to a submission-ready state.

1.
HIGHrigor
Add vendor, catalog number, clone, and RRID for all antibodies used in flow cytometry (CD105, CD73, CD90, CD45, CD34, CD11b, CD31, HLA-DR) to the Methods section.
Antibody identification is essential for reproducibility; missing these details is a key resource gap.
2.
HIGHrigor
Explicitly report mycoplasma testing (method and result) for each batch of mesenchymal stem cells in the Methods section.
Mycoplasma contamination is a known issue in cell therapy; its absence is a key resource gap.
3.
HIGHrigor
Provide a standard identifier (e.g., cell bank accession number, RRID) for the Wharton's jelly-derived mesenchymal stem cell product to improve traceability.
A unique identifier for the cell product is essential for reproducibility and regulatory compliance.
4.
HIGHstatistics
Correct or clarify the annual incidence rate for heart failure in the control group (Table 2: 37 events/551.88 person-years gives 6.71, not 6.48).
This discrepancy suggests a possible transcription error that could affect the reported effect size.
5.
HIGHreporting
Include the significance level (alpha) and desired power in the sample size calculation description to make the power analysis fully adequate.
A complete power analysis is a standard requirement for clinical trial reporting.
6.
HIGHreporting
Provide a scientific justification for the predominance of male participants in the study, or acknowledge the lack of female representation as a limitation with an explanation of why it occurred.
Sex imbalance without justification is a biological variable reporting gap.
7.
HIGHreporting
Report race/ethnicity data for the study population, or state why it was not collected.
Race/ethnicity is important for generalizability and is a standard demographic variable.
8.
HIGHstatistics
Report the results of normality tests (Shapiro-Wilk/Kruskal-Wallis) in a supplementary table, and describe the explicit action taken when assumptions were violated.
Assumption verification is incomplete without reporting the test results and subsequent actions.
9.
HIGHstatistics
Report exact p-values (e.g., P=0.100 instead of P=0.10) for all outcomes, including non-significant ones.
Threshold p-values are less informative and can obscure the strength of evidence.
10.
HIGHcopyedit
Fix the apparent transcription errors in Table 1: '18 (134)' for eGFR <60 in intervention group should likely be '18 (13)'; '39 (1)' for control should likely be '39 (15)'.
These percentages are nonsensical and will be flagged by any careful reader or reviewer.
11.
HIGHcopyedit
Correct the unit for eGFR from 'mm/min/1.73 m2' to 'mL/min/1.73 m2' in Table 1.
The standard unit is mL/min/1.73 m2, not mm/min.
12.
HIGHcopyedit
Fix missing closing parentheses in Table 2 for cumulative probability values in the control column (e.g., '16.08 (10.90 to 21.27' should be '16.08 (10.90 to 21.27)').
Missing parentheses are formatting errors that reduce readability.
13.
MEDIUMreporting
Add a statement on outlier handling in the statistical analysis section, specifying any pre-specified rules for excluding data points.
Outlier handling is a standard element of statistical analysis reporting.
14.
MEDIUMreporting
In the Discussion, explicitly mention that the study was not powered to detect subgroup effects (relevant for the sex interaction discussion).
This caveat is important for interpreting subgroup analyses.
15.
LOWreporting
Consider providing a CONSORT flow diagram with exact reasons for each exclusion (already included in Figure 1, but ensure numbers sum correctly).
A complete CONSORT flow diagram is a standard requirement for RCT reporting.

Full text (70,337 chars)Analyzed: Jul 6, 2026

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