The DOI matches its Crossref record; 30 of the 32 references it cites were found in a registry or an index; 7 of the 17 sources its claims cite were checked for support.
Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure
Open accessAbstract
Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.
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Claims the paper makes
21 Own result · 17 Own method · 6 Sources not found · 3 Supported · 3 Partly supported · 3 No full text of the sources · 2 Own interpretation · 1 Couldn’t confirm · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“First, CITRIS-ALI as proposed was based on a previously performed phase 1 safety trial of vitamin C administered to patients in the very early stages of severe sepsis, not ARDS.15”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
What the sources say
- Partly supportedcites [15] 15. Fowler AA III, Syed AA, Knowlson S, et al; Medical Respiratory Intensive Care Unit Nursing. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12: 32. doi:10.1186/1479-5876-12-32 sourceExperimental — accuracy not yet measured
The Methods (Patient enrollment) describe a phase I intravenous ascorbic acid trial in patients meeting severe-sepsis criteria within 48 hours of ICU admission, supporting the description of an early severe-sepsis trial. But the Results (Enrolled study patients) state that 19 patients had ARDS at entry, contradicting the claim’s “not ARDS” qualification. This paper does not establish what CITRIS-ALI was based on. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Delayed quantification of these biomarkers in CITRIS-ALI compared with early vitamin C infusion in severe sepsis may explain results discordant with those of previous studies of vitamin C in severe sepsis.15”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Supportedcites [15] 15. Fowler AA III, Syed AA, Knowlson S, et al; Medical Respiratory Intensive Care Unit Nursing. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12: 32. doi:10.1186/1479-5876-12-32 sourceExperimental — accuracy not yet measured
The Methods (Patient enrollment; page unavailable) report that intravenous ascorbic acid began 2–4 hours after randomization in patients with severe sepsis. The Results (Impact of ascorbic acid infusion on biomarkers; page unavailable) report early reductions in CRP and procalcitonin. The comparison with CITRIS-ALI and the proposed explanation for discordant results are the citing authors’ inference, not a finding attributed to this 2014 trial. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: C-reactive protein and thrombomodulin are valid biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, vitamin C prevented neutrophil extracellular trap formation, a biological event in activated neutrophils that promotes vascular injury.25”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Partly supportedcites [25] 25. Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C: a novel regulator of neutrophil extracellular trap formation. Nutrients. 2013;5(8): 3131-3151. doi:10.3390/nu5083131 sourceExperimental — accuracy not yet measured
The Results (section 3.7) show that vitamin C significantly reduced NET formation in activated human neutrophils, rather than preventing it entirely. The Discussion (section 4) describes potential damage to lung endothelial cells from NET formation in septic mice, but does not establish vascular injury as an observed outcome. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Trans- fer out of the ICU by hour 168 or less occurred in 25% of pa- tients in the vitamin C group (21/84) vs 12.5% in the placebo group (10/83) (χ 2 = 4.63; P = .03; difference, 12.95% [95% CI, 1.16% to 24.73%; P = .31]).”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours”
- Also stated in: § Primary Outcomes · plain
“There was no statistically significant difference in mSOFA scores between placebo and the vitamin C-infused patients from enrollment to 96 hours”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The modified Sequential Organ Failure Assessment score is a valid measure of organ failure in patients with sepsis and ARDS.
- Also stated in: § Primary Outcomes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No unexpected study-related adverse events occurred during the trial.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Adverse Events
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33)”
- Also stated in: § Primary Outcomes · plain
“There were no significant differences between the vitamin C group and placebo group in the C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94; 95% CI, -8.23 to 24.1; P = .33)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: C-reactive protein and thrombomodulin are valid biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.
- Also stated in: § Primary Outcomes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Forty-three of the 46 prespecified secondary outcomes were not significantly different between the vitamin C group and the placebo group”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Kaplan-Meier survival curves for the 2 groups were significantly different by the Wilcoxon test (χ 2 1 = 6.5;P = .01).”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70)at 168 hours”
- Also stated in: § Primary Outcomes · plain
“or thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69; 95% CI, -2.8 to 4.2; P = .70)assessed at 168 hours”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: C-reactive protein and thrombomodulin are valid biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.
- Also stated in: § Primary Outcomes · plain
- It may state two separate claims as one. 24
- Probably not a substantial claim. 21
- The quote only partly states this claim. 2
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In accordance with these calculations, CITRIS-ALI enrolled 170 patients (85 per group) to allow for 10% dropouts, providing a statistical power of 80%, with an α < .05.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Statistical Analysis
What the sources say
- Could not verifycites [15] 15. Fowler AA III, Syed AA, Knowlson S, et al; Medical Respiratory Intensive Care Unit Nursing. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12: 32. doi:10.1186/1479-5876-12-32 sourceExperimental — accuracy not yet measured
The Results (Enrolled study patients; page unavailable) describe this source’s own trial, which enrolled 26 patients in three groups, not CITRIS-ALI. The Methods (Statistical analysis; page unavailable) give no CITRIS-ALI sample-size calculation. Searches for CITRIS-ALI, 170 patients, simulations, and power found no passage addressing the claim. (LLM, conf=0.76)
plainn = 170- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“for instance, the LUNG SAFE study reported 34% to 45% mortality.5”
- Also stated in: § Discussion · plain
“in the LUNG SAFE study, which included more than 3000 patients with ARDS in 50 countries, all-cause mortality remained high, varying from 34% to 46%, depending on ARDS severity.5”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
What the sources say
- Supportedcites [5] 5. Bellani G, Laffey JG, Pham T, et al; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788- 800. doi:10.1001/jama.2016.0291 source
The Results (p. 1) report hospital mortality of 34.9% for mild, 40.3% for moderate, and 46.1% for severe ARDS. These figures support the claim’s approximate 34%–46% range by severity. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Discussion · plain
Every source the paper cites for this claim was checked and supports it.
In the paper
“The selection of the primary outcomes was based on a previously performed phase 1 trial.15”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Key Points
What the sources say
- Supportedcites [15] 15. Fowler AA III, Syed AA, Knowlson S, et al; Medical Respiratory Intensive Care Unit Nursing. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12: 32. doi:10.1186/1479-5876-12-32 source
The Abstract > Background identifies this study as a phase I trial in patients with severe sepsis. The Abstract > Methods names its primary safety and tolerability endpoints and the additional outcomes it monitored, supporting its identification as the earlier trial used to inform outcome selection. Our copy has no page numbers for these passages. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A report from US hospitals revealed declining ARDS mortality, likely because of both improved supportive care and regimented approaches to mechanical ventilation.4”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Partly supportedcites [4] 4. Cochi SE, Kempker JA, Annangi S, Kramer MR, Martin GS. Mortality trends of acute respiratory distress syndrome in the United States from 1999 to 2013. Ann Am Thorac Soc. 2016;13(10):1742-1751. doi:10.1513/AnnalsATS.201512-841OC sourceExperimental — accuracy not yet measured
The Results report a decline in U.S. ARDS-related deaths and age-adjusted mortality rates from 1999 to 2013. But the study used national death certificates, not a report from hospitals, and the Discussion (Dataset) says it cannot determine the reasons for the decline. It does not establish improved supportive care or mechanical-ventilation approaches as causes. (LLM, conf=0.89)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After cessation of vitamin C infusion at 96 hours, vitamin C levels declined but remained significantly elevated at hour 168 (median, 46 μmol/L; IQR, 19-66) compared with placebo”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At day 28, mortality was 46.3% (38/82) in the placebo group vs 29.8% (25/84) in the vitamin C group (χ 2 = 4.84; P = .03;between-group difference, 16.58% [95% CI, 2% to 31.1%])”
- Also stated in: § Discussion · plain
“although vita-min C compared with placebo was associated with a significant reduction in 28-day all-cause mortality”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma vitamin C levels sampled at trough periods before infusion had increased significantly in vitamin C-infused patients by hours 48 (median, 166 μmol/L; IQR, 88-376) and 96 (median, 169 μmol/L; IQR, 87-412) compared with placebo patients by hours 48 (median, 23 μmol/L; IQR, 9-37) and 96 (median, 26 μmol/L; IQR, 9-41)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of hospital-free days in the vitamin C group vs the placebo group was 22.6 vs 15.5, respectively (mean difference, 6.69; 95% CI, 0.3 to 13.8; P = .04)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Two patients were lost to follow-up.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Primary Outcomes
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma vitamin C levels in all patients were subnormal at enrollment (<28 μmol/L), with no significant difference between groups (median for vitamin C-infused patients vs placebo, 22 vs 22 μmol/L [interquartile range {IQR}, 8-39 vs 11-37]; P = .49).”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of ventilator-free days was 13.1 in the vitamin C group vs 10.6 in the placebo group (mean difference, 2.47;”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
plainn = 167- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of ICU-free days to day 28 was 10.7 in the vita- min C group vs 7.7 in the placebo group (mean difference, 3.2; 95% CI, 0.3 to 5.9; P = .03)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Vitamin C-infused patients exhibited a significant reduction in 28-day all-cause mortality, although the P value was not adjusted for multiple comparisons.”
- Also stated in: § Conclusions · plain
“All-cause mortality to day 28, % | | | 84 | 29.8 | 38 | 82 | 46.3 | -0.17 | .03”
- Also stated in: § Limitations · plain
“Gehan-Breslow-Wilcoxon test, P = .01HR, 0.55 (95% CI, 0.33-0.90)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Conclusions · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Significance was set at α = .05and a Holm-Bonferroni correction for 3 co-primary end points was conducted.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fourth, the dosage of vitamin C used in this trial (50 mg/kg every 6 hours for 96 hours) may be insufficient for optimal care of sepsisassociated ARDS.Higher vitamin C dosages or longer administration times may have produced different results.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Multiple imputation with a pattern-mixture model with control-based pattern imputation was used, with 50 imputed data sets created and analyzed to examine the effect of monotone missing data.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blinding was maintained by the investigational pharmacy at each institution.Investigators were blinded from onset of enrollment to completed analysis of primary and secondary outcomes.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Randomization, Masking, and Study Drug Administration
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because of a potential for type I error caused by multiple comparisons, findings for analyses of secondary end points should be interpreted as exploratory.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients were randomized 1:1 to receive vitamin C or placebo (Figure 1), using randomization generated by the VCU Health Investigational Drug Service by means of Research Randomizer at http://www.randomizer.org.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Randomization, Masking, and Study Drug Administration
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For organ system failure, the SOFA score was modified, eliminating bilirubin during the blinded analysis period as a result of many missing values because clinicians determined that bilirubin measurement was not clinically indicated (mSOFA, range from 0 [normal organ function] to 20 [worst organ function]).”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Study Measurements and Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: The modified Sequential Organ Failure Assessment score is a valid measure of organ failure in patients with sepsis and ARDS.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Fifth, given the absence of previous clinical data, this proof-ofconcept trial was designed to measure the effect of ascorbic acid on organ failure and laboratory measures of inflammation in patients with severe sepsis rather than mortality.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CITRIS-ALI enrollment required fully developed ARDS with endotracheal intubation, which could have delayed vitamin C administration in the treatment group and possibly limited the ability to detect an effect on mSOFA scores and biomarkers.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Three patients were excluded after randomization because of a subsequent diagnosis of diffuse alveolar hemorrhage (n = 2) and acute eosinophilic pneumonia (n = 1).None of these patients received vitamin C.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Characteristics of the Patients
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, differences in baseline characteristics of this necessarily heterogeneous population may have influenced mortality.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sixth, death and ICU graduation rates between the 2 groups were dissimilar, thus rendering the results susceptible to internal selection bias.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vitamin C increased alveolar fluid clearance by preventing activated neutrophil accumulation in alveolar spaces, limiting alveolar epithelial water-channel damage, and promoting their increased expression.14”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Not checked — no full text of the sourcecites [14] 14. Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide- induced acute lung injury. Crit Care Med. 2011;39 (6):1454-1460. doi:10.1097/CCM.0b013e3182120cb8 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“A cute respiratory distress syndrome (ARDS) is a common sepsis-associated organ injury and results in significant mortality [1][2][3][4]”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
What the sources say
- Not matchedcites [1][2][3][4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The median observation time was 28 days (interquartile range, 15-28 days) for the vitamin C group and 28 days (interquartile range, 5-28 days) for the placebo group.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury.[13][14][15]”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Abstract
What the sources say
- Not matchedcites [13][14][15]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Patients with sepsis and acute respiratory distress syndrome have worse clinical outcomes than those without sepsis and ARDS, with higher 30-and 60-day mortality and with fewer ventilatorand ICU-free days.27”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Sheu CC, Gong MN, Zhai R, et al. Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. Chest. 2010;138(3):559- 567. doi:10.1378/chest.09-2933
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Patients with sepsis have a high mortality and accounted for $23.7 billion in US hospital costs in 2013.26”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Discussion
What the sources say
- Not matchedcites [26] 26. Torio C, Moore B. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013: Statistical Brief #204. Rockville, MD: Agency for Healthcare Research & Quality; 2006-2016.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The CITRIS-ALI protocol was approved by the institutional review boards at each of 7 participating medical centers.Written informed consent was obtained from patients or patients' legally authorized representatives.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Study Oversight
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The modified Sequential Organ Failure Assessment score is a valid measure of organ failure in patients with sepsis and ARDS.
“For organ system failure, the SOFA score was modified, eliminating bilirubin during the blinded analysis period as a result of many missing values because clinicians determined that bilirubin measurement was not clinically indicated (mSOFA, range from 0 [normal organ function] to 20 [worst organ function]).”
The paper relies on this without support.
C-reactive protein and thrombomodulin are valid biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.
“plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The recent clinical trial did not find the effect of intravenous vitamin C infusion on organ failure and biological markers of inflammation and vascular injury in patients with sepsis and acute respiratory distress syndrome, but vitamin C compared with the placebo was associated with a significant reduction in 28-day all-cause mortality [199].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [199]
In the citing paper
“One study reported reduced vasopressor use at 168 h [523].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [523]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
“median at baseline, 22 vs 22 μM [IQR, 8-39 vs 11-37], P = .68”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
“22 vs 22 μmol/L [interquartile range {IQR}, 8-39 vs 11-37]; P = .49”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“25% of pa- tients in the vitamin C group (21/84) vs 12.5% in the placebo group (10/83)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
Reported 12.5 · recomputed 12.048193
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Characteristics of the Patients
“A total of 1262 eligible patients were identified, of whom 1062 were excluded because of the diagnoses listed in Figure 1.”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Statistical Analysis
“1262 Patients screened for eligibility 1092 Excluded”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“| Net fluid balance to median (IQR), mL | 0 | 83 | 1604 | 2927 | 79 | 1901 | 3034 | -3759 (-1123 to 373) | .32 |”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Conclusions
Reported -3759 · recomputed -375
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
“(χ 2 = 4.63; P = .03; difference, 12.95% [95% CI, 1.16% to 24.73%; P = .31])”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Secondary Outcomes
“(χ 2 = 4.63; P = .03;”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Key Points
“oxygenation index (FiO 2 × mean airway pressure/PO 2 ) (if ventilated)”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Conclusions
“e FiO 2 × mean airway pressure/PO 2 × 100.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
“Plasma vitamin C levels in all patients were subnormal at enrollment (<28 μmol/L), with no significant difference between groups”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Vitamin C Pharmacokinetic Findings
“median for vitamin C-infused patients vs placebo, 22 vs 22 μmol/L [interquartile range {IQR}, 8-39 vs 11-37]”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“| | 168 | 72 | 22.2 | | 59 | 10.2 | | 10 | .07 |”
§ Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure The CITRIS-ALI Randomized Clinical Trial > Conclusions
Reported 10 · recomputed 12
Citations
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Dietary Supplements for COVID-19
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“However, mortality, which was one of the forty-six pre-specified secondary endpoints, was significantly lower with vitamin C [40] .”
BackgroundAscorbic Acid in the Acute Care Setting
Kressin, C., Pandya, K. A., Magnuson, B. L., Donaldson, C., & Flannery, A. H. (2021) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2102 · Cited by 17
Schlapbach, L. J., GIBBONS, K. S., Ridolfi, R., Harley, A., Cree, M., Long, D. A., Buckley, D. H. F., Erickson, S. J., Festa, M., George, S., et al. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.663435 · Cited by 17
No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
Zheng, S., Chen, Q., Jiang, H., Guo, C., Luo, J., Li, S., Wang, H., Li, H., Zheng, X., & Weng, Z. (2021) · Open Medicine · doi:10.1515/med-2021-0361 · Cited by 16
“However, a recent randomized controlled trial (RCT) study on patients with sepsis and ARDS demonstrated that high-dose vitamin C (50mg/kg four times a day for 4 days) use did not significantly ameliorate organ failure scores or alter the levels of biomarkers for inflammation compared with patients in placebo groups [2…”
BackgroundAscorbic acid attenuates activation and cytokine production in sepsis-like monocytes
Schmidt, T., Kahn, R., & Kahn, F. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ab0521-243r · Cited by 17
Wang, R., Qi, B., Zhang, X., et al. (2022) · European journal of medical research · doi:10.1186/s40001-022-00652-9 · Cited by 16
“lung trauma [22], among which shock, external trauma and infection have been reported as the most common causes [23, 24].”
BackgroundDriny, W. A. E., Esmat, I. M., Shaheen, S. M., & Sabri, N. A. (2022) · Anesthesiology Research and Practice · doi:10.1155/2022/4057215 · Cited by 16
“and assessment for unassisted breathing [17].”
BackgroundMethodInfluentialVitamin C as a treatment for organ failure in sepsis
Wang, Z., Liu, L., & Liu, L. (2023) · European journal of medical research · doi:10.1186/s40001-023-01183-7 · Cited by 16
“The treatment group received 50 mg/kg of vitamin C intravenously every 6 h for 96 h, showing a substantial reduction in 28 day mortality [39].”
MethodZeng, Y., Liu, Z., Xu, F., & Tang, Z. (2023) · Medicine · doi:10.1097/md.0000000000035648 · Cited by 16
May, C. N., Ow, C. P. C., Pustovit, R. V., Lane, D. J. R., Jufar, A. H., Trask-Marino, A. L., Peiris, R. M., Gunn, A. P., Booth, L. C., Plummer, M. P., et al. (2024) · British Journal of Anaesthesia · doi:10.1016/j.bja.2024.04.058 · Cited by 17
Better Preventing and Mitigating the Effects of Covid-19
Maguire, G. (2020) · Future Science OA · doi:10.2144/fsoa-2020-0051 · Cited by 16
Reply: Vitamin C as a Possible Therapy for COVID-19
Kim, S. B., & Yeom, J. (2020) · Infection and Chemotherapy · doi:10.3947/ic.2020.52.2.224 · Cited by 16
“However, secondary outcome measures did differ between the groups with 28-day all-cause mortality significantly lower and intensive care unit-free days significantly shorter in the placebo groups than in the Vit-C groups [5].”
BackgroundSafabakhsh, M., Imani, H., Shahinfar, H., Mohammadpour, M., Rohani, P., & Shab‐Bidar, S. (2024) · Clinical Nutrition · doi:10.1016/j.clnu.2024.03.030 · Cited by 18
Kumar, V., Bhushan, D., Supriya, S., Ganapule, A., Lohani, P., Shyama, S., Pandey, S., Majhi, P. K., Anand, U., Kumar, R., et al. (2022) · Journal of Family Medicine and Primary Care · doi:10.4103/jfmpc.jfmpc_2437_21 · Cited by 15
Zeng, J., Liu, J., Huang, J., Fu, S., Wang, X.-Y., Xi, C., Cui, Y.-R., & Qu, F. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110142 · Cited by 15
CITRIS-ALI: How statistics were used to obfuscate the true findings
Marik, P. E., & Payen, D. M. (2019) · Anaesthesia Critical Care & Pain Medicine · doi:10.1016/j.accpm.2019.10.004 · Cited by 18
Targeting of G-protein coupled receptors in sepsis
Rehman, A., Baloch, N. U.-A., Morrow, J., Pacher, P., & Haskó, G. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107529 · Cited by 18
Antibiotic treatment in patients with sepsis: a narrative review
Plata-Menchaca, E. P., Ferrer, R., Ruiz‐Rodríguez, J. C., Morais, R., & Póvoa, P. M. S. R. (2020) · Hospital Practice · doi:10.1080/21548331.2020.1791541 · Cited by 17
Karcıoğlu, O., Yüksel, A., Baha, A., Er, A. B., Esendagli, D. R., Gülhan, P. Y., Karaoğlanoğlu, S., Erçelik, M., Şerifoğlu, İ., Yıldız, E., et al. (2020) · Turkish Thoracic Journal · doi:10.5152/turkthoracj.2020.20069 · Cited by 16
“In that trial, there was no difference in the sequential organ failure assessment score and 28-day mortality between the vitamin C and placebo groups [60].”
BackgroundHe, J., Zheng, G., Qian, X., Sheng, H., Chen, B., Zhao, B., Chen, E., Mao, E., & Bian, X. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.1887832 · Cited by 15
Trace Minerals, Vitamins and Nutraceuticals in Prevention and Treatment of COVID-19
Srivastava, A., Gupta, R. C., Doss, R. B., & Lall, R. (2021) · Journal of Dietary Supplements · doi:10.1080/19390211.2021.1890662 · Cited by 16
“Several studies have revealed its beneficial role in preventing pneumonia and sepsis (Fowler et al. 2014, 2019).”
BackgroundHan, Q.-Q., Deng, M., Liu, H., Ali, U., Li, X.-Y., & Wang, Y. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114600 · Cited by 15
Soares, V. E. M., do Carmo, T. I. T., dos Anjos, F., Wruck, J., Maciel, S. F. V. D. O., Bagatini, M. D., & Silva, D. T. D. R. E. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04263-6 · Cited by 17
Inhibition of Prostaglandin F2α Receptors Exaggerates HCl-Induced Lung Inflammation in Mice
Maehara, T., & Fujimori, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312843 · Cited by 15
“According to previous reports, the mortality rate of ALI/ARDS has remained high [5,27].”
BackgroundInfluentialRole of ascorbic acid infusion in critically ill patients with transfusion‐related acute lung injury
Kassem, A. B., Ahmed, I., Omran, G. A., Megahed, M., & Habib, T. N. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15167 · Cited by 17
“635 for two independent means of CRP (twotailed t-test).(30) This double-blind RCT (participant, care provider) was carried out on 80 adult (18-64 years) critically ill patients diagnosed with TRALI within 6 hours of transfusion at the ICU units of two tertiary hospitals between November 2019 and July 2021.”
MethodResultInfluentialTang, S., Jiang, J., Zhang, N., et al. (2020) · Microvascular Research · doi:10.1016/j.mvr.2020.104093 · Cited by 15
“The most common causes of ARDS are pneumonia, aspiration of liquid contents, septicemia, acute liver failure, and acute pancreatitis, which directly or indirectly induce lung injury (Matthay et al., 2020; Fowler 3rd et al., 2019; Yang et al., 2019).”
BackgroundEmerging cellular and pharmacologic therapies for acute respiratory distress syndrome
Gonzalez, H., Horie, S., & Laffey, J. G. (2020) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000784 · Cited by 14
Gholizadeh, M., Saeedy, S. A. G., Abdi, A., Khademi, F., Lorian, K., Clark, C. C. T., & Djafarian, K. (2021) · Clinical Nutrition Open Science · doi:10.1016/j.nutos.2021.09.003 · Cited by 15
Labbani‐Motlagh, Z., Amini, S., Aliannejad, R., Sadeghı, A., Shafiee, G., Heshmat, R., Jafary, M., Talaschian, M., Akhtari, M., Jamshidi, A., et al. (2022) · Journal of Research in Pharmacy Practice · doi:10.4103/jrpp.jrpp_30_22 · Cited by 14
“[22] Clinical trials on high-dose Vitamin C have reported no major side effects.[1,14,15] Based on the evidence, nephrolithiasis and oxaluria are no longer concerning adverse events.”
BackgroundMethodResultInfluentialSun, M., Zeng, Z., Xu, G., An, S. L., Deng, Z., Cheng, R., Yao, Y., Wu, J., Hu, H., Huang, Q., et al. (2023) · Shock · doi:10.1097/shk.0000000000002206 · Cited by 14
“Despite significant improvements in the intensive care unit, treatment options for patients with sepsis are extremely limited, and ALI/ARDS, the hallmark of sepsis, is one of the leading causes of death (26).”
BackgroundCyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway
Lin, M., Xie, W., Xiong, D., et al. (2023) · Chinese Medicine · doi:10.1186/s13020-023-00837-2 · Cited by 14
“ALI/ARDS is the most common form of multi-organ dysfunction syndrome and an influential driver of sepsis morbidity and mortality [2].”
BackgroundMarmiere, M., D’Amico, F., Monti, G., & Landoni, G. (2024) · Critical Care Medicine · doi:10.1097/ccm.0000000000006532 · Cited by 14
“As a result, some RCTs opt for modified versions of the SOFA score, excluding certain subscores from the total (10, 17, 20, 22).”
The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024
Shime, N., Nakada, T., Yatabe, T., Yamakawa, K., Aoki, Y., Inoue, S., Iba, T., Ogura, H., Kawai, Y., Kawaguchi, A., et al. (2025) · Acute Medicine & Surgery · doi:10.1002/ams2.70037 · Cited by 20
Wu, T., Wang, T., Jiang, J., Tang, Y., Zhang, L., Jiang, Z., Liu, F., Kong, G., Zhou, T., Liu, R., et al. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s506549 · Cited by 16
“In addition, the mortality rate in our placebo group was 27.8%, which was in the acceptable range compared with previous studies, 26,27 implying the generalizability of our results.”
InfluentialVandervelden, S., Cortens, B., Fieuws, S., Eegdeman, W., Malinverni, S., Vanhove, P., Monsieurs, K. G., Breuls, J., Hubloue, I., Stifkens, F., et al. (2025) · Critical Care · doi:10.1186/s13054-025-05383-x · Cited by 15
Current status of COVID-19 treatment: An opinion review
Franco, S. D., Alfieri, A., Petrou, S., et al. (2020) · World Journal of Virology · doi:10.5501/wjv.v9.i3.27 · Cited by 14
Updates in Sepsis Resuscitation
Ellender, T. J., & Benzoni, N. S. (2020) · Emergency Medicine Clinics of North America · doi:10.1016/j.emc.2020.06.006 · Cited by 14
Systemic inflammatory response in cardiac surgery
Krichevskiy, L. А., Rybakov, V. Y., Dvoryadkin, A. A., & Николаевич, П. Д. (2021) · Russian Journal of Anesthesiology and Reanimatology · doi:10.17116/anaesthesiology202103194 · Cited by 15
Agarwal, A., Basmaji, J., Fernando, S. M., Ge, F. Z., Xiao, Y., Faisal, H., Honarmand, K., Hylands, M., Lau, V. I., Lewis, K. A., et al. (2021) · JMIR Research Protocols · doi:10.2196/33989 · Cited by 14
Toledano, J. M., Moreno‐Fernández, J., Puche-Juárez, M., Ochoa, J. J., & Díaz‐Castro, J. (2021) · Antioxidants · doi:10.3390/antiox11010005 · Cited by 15
“This will conceivably improve long-term outcomes, especially if they keep on taking the vitamin orally after ICU discharge [62,71].”
BackgroundMulti-Level Immune Support by Vitamins C and D during the SARS-CoV-2 Pandemic
Carr, A. C., & Gombart, A. F. (2022) · Nutrients · doi:10.3390/nu14030689 · Cited by 14
Levine, M. N., Ebenuwa, I., & Violet, P.-C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-805378-2.00018-8 · Cited by 17
Intravenous vitamin C in adults with sepsis in the intensive care unit: still LOV’IT?
Stoppe, C., Preiser, J., Backer, D. D., & Elke, G. (2022) · Critical Care · doi:10.1186/s13054-022-04106-w · Cited by 16
Effect of vitamin C in critically ill patients with sepsis and septic shock: A meta-analysis
Feng, F., Yang, H., Yang, W., Li, M., Chang, X., & Chen, Y. (2021) · Science Progress · doi:10.1177/0036850421998175 · Cited by 15
Sepsis-induced ALI/ARDS beyond supportive care: molecular mechanisms and cutting-edge therapies
Barkat, M. Q., Li, Q., Manzoor, M., Xu, C., Hussain, N., Salawi, A., Yang, H., & Hussain, M. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115495 · Cited by 17
The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?
Grudlewska‐Buda, K., Wiktorczyk-Kapischke, N., Budzyńska, A., Kwiecińska-Piróg, J., Przekwas, J., Kijewska, A., Sabiniarz, D., Gospodarek-Komkowska, E., & Skowron, K. (2022) · Antioxidants · doi:10.3390/antiox11071247 · Cited by 13
Xu, C., Yi, T., Tan, S., Xu, H., Hu, Y., Ma, J., & Xu, J. (2023) · Nutrients · doi:10.3390/nu15081848 · Cited by 13
From Emergence to Endemicity: A Comprehensive Review of COVID-19
Naik, R., Avula, S., Palleti, S. K., Gummadi, J., Ramachandran, R., Chandramohan, D., Dhillon, G. S., Gill, A. S., Paiwal, K., Shaik, B. F., et al. (2023) · Cureus · doi:10.7759/cureus.48046 · Cited by 17
Oshima, K., Gravio, C. D., Yan, B., McMurty, S. A., Burke, R. C., Levoir, L. M., Kravitz, M. S., Stephenson, D., Issaian, A., Hansen, K. C., et al. (2025) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202501-012oc · Cited by 16
Rozemeijer, S., de Grooth, H., Elbers, P., Girbes, A. R. J., den Uil, C. A., Dubois, E. A., Wils, E., Rettig, T. C. D., van Zanten, A. R. H., Vink, R., et al. (2021) · Trials · doi:10.1186/s13063-021-05483-3 · Cited by 13
“High-dose intravenous vitamin C alone [17, 18], or in combination with thiamine and hydrocortisone [19, 20], improved organ failure recovery, shock reversal, and survival.”
BackgroundHigh-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study
Xia, G., Qin, B., Ma, C., Zhu, Y., & Zheng, Q. (2021) · Aging · doi:10.18632/aging.203503 · Cited by 14
“Although there is no universally adopted dosage definition, we recommended intravenous administration of a 6-day course of 100 mg/kg every 6 hours for 1 day followed by 100 mg/kg every 12 hours for additional 5 days as the optimum dosage of vitamin C therapy as described in the recently published randomized controlled…”
BackgroundMethodEarly ascorbic acid administration prevents vascular endothelial cell damage in septic mice
Madokoro, Y., Kamikokuryo, C., Niiyama, S., Ito, T., Hara, S., Ichinose, H., & Kakihana, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.929448 · Cited by 17
Chen, C.-Y., Chiu, C.-T., Lee, H.-S., & Lai, C. (2022) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2022.11.015 · Cited by 14
MicroRNA‑139‑5p improves sepsis‑induced lung injury by targeting Rho‑kinase1
Zhao, X., Wang, M., Sun, Z., Zhuang, S., Zhang, W., Yang, Z., Han, X., & Nie, S. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10493 · Cited by 13
Djordjevic, B., Milenković, J., Stojanovic, D., Velickov, A., Djindjić, B., & Stoimenov, T. J. (2022) · British Journal Of Nutrition · doi:10.1017/s0007114522000083 · Cited by 20
“* Corresponding author: Branka Djordjevic, email brankadjordjevic83@gmail.com † These authors contributed equally to this work Abbreviations: ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; NET, neutrophils extracellular traps; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2;…”
BackgroundInfluentialCausal effects of genetically vitamins and sepsis risk: a two-sample Mendelian randomization study
Lou, C., Meng, Z., Shi, Y., Zheng, R., Pan, J., & Qian, S. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-023-08778-9 · Cited by 12
“Infusion of vitamin C for 96 h also fail to enhance scores for organ dysfunction and reduce damage to the vascular system and inflammatory markers [25].”
BackgroundPrivšek, M., Strnad, M., & Markota, A. (2024) · Medicina · doi:10.3390/medicina60010103 · Cited by 13
Li, W., Zhao, R., Liu, S., Ma, C., & Wan, X. (2024) · Medicine · doi:10.1097/md.0000000000037838 · Cited by 14
“[25] However, vitamin C did not reduce the SOFA score or biomarker levels even at high doses.”
BackgroundWu, X., & Guo, Y. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s488463 · Cited by 12
The Complex Interplay between Immunonutrition, Mast Cells, and Histamine Signaling in COVID-19
Kakavas, S., Karayiannis, D., & Mastora, Z. (2021) · Nutrients · doi:10.3390/nu13103458 · Cited by 12
“C supplementation in septic shock and ARDS [68,69].”
InfluentialYao, R.-Q., Zhu, Y., Yu, Y. S., Li, Z., Wang, L., Zheng, L., Li, J., Huang, H., Wu, G., Zhu, F., et al. (2021) · Burns & Trauma · doi:10.1093/burnst/tkab040 · Cited by 13
“The results from a recently published large RCT (CITRIS-ALI) revealed significantly reduced mortality rates in sepsis patients receiving vitamin C monotherapy, and follow-up analysis found reduced SOFA scores at 96 h [61,62].”
Bias against Vitamin C in Mainstream Medicine: Examples from Trials of Vitamin C for Infections
Hemilä, H., & Chalker, E. (2022) · Life · doi:10.3390/life12010062 · Cited by 13
Oxygen therapy for sepsis and prevention of complications
Minasyan, H. A. (2022) · Acute and Critical Care · doi:10.4266/acc.2021.01200 · Cited by 15
“Vitamin C has a protective effect against oxidative stress in sepsis and septic shock [123].”
BackgroundHe, S., Shi, J., Liu, W., Du, S., Zhang, Y., Gong, L., Dong, S., Li, X., Gao, Q., Yang, J., et al. (2022) · Inflammation Research · doi:10.1007/s00011-022-01605-y · Cited by 12
“Pulmonary is one of the most susceptible target organs in response to sepsis, with a mortality rate as high as 35–46% [2, 3].”
BackgroundRemote ischemic conditioning in septic shock: the RECO-Sepsis randomized clinical trial
Cour, M., Klouche, K., Souweine, B., Quenot, J., Schwebel, C., Périnel, S., Amaz, C., Buisson, M., Ovize, M., Mewton, N., et al. (2022) · Intensive Care Medicine · doi:10.1007/s00134-022-06872-1 · Cited by 11
Nandhini, N., Malviya, D., Parashar, S., Pandey, C., Nath, S. S., & Tripathi, M. K. (2022) · International Journal of Critical Illness and Injury Science · doi:10.4103/ijciis.ijciis_107_21 · Cited by 13
“[18] However, the same authors, 5 years later, in the double‐blind multicentric CITRIS‐ALI randomized controlled trial, compared 50 mg/kg of AA with placebo, failed to find any significant difference in SOFA scores, biomarkers of inflammation and vascular injury (C‐reactive protein and thrombomodulin) in patients with…”
ResultKato, T., MIZUNO, T., NAKANISHI, M., Lee, J. K., Yamada, S., Tsuboi, N., & Takahashi, K. (2023) · In Vivo · doi:10.21873/invivo.13200 · Cited by 14
Pharmacological management of adult patients with acute respiratory distress syndrome
Matera, M. G., Rogliani, P., Bianco, A., & Cazzola, M. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1801636 · Cited by 13
Nephrotic Syndrome Complications - New and Old. Part 2.
Stancioiu, F., Ivanescu, B., & Dumitrescu, R. (2022) · PubMed · doi:10.26574/maedica.2022.17.2.395 · Cited by 12
Nie, Y., Liang, J., Sun, J., Li, J., Zhai, X., & Zhao, P. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111018 · Cited by 10
Eligibility Criteria of Randomized Clinical Trials in Critical Care Medicine
Heirali, A., Heybati, K., Sereeyotin, J., Khan, F. A., Yarnell, C. J., Krewulak, K. D., Murthy, S., Burns, K. E. A., Fowler, R., Fiest, K. M., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.54944 · Cited by 12
Platelet membrane-cloaked biomimetic nanoparticles for targeted acute lung injury therapy
Lin, P., Gao, R., Yang, W., et al. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.114542 · Cited by 11
Advances in anti-inflammatory treatment of sepsis-associated acute respiratory distress syndrome
Zhang, N., Zhang, H., Li, Y., & Fu, Q. (2025) · Inflammation Research · doi:10.1007/s00011-025-02043-2 · Cited by 14
Zhang, C., Yang, H., Liu, X., Wu, R., Zong, H., Wu, E., Zhou, Y. K., Li, J., & Shen, B. (2025) · Journal of Medical Internet Research · doi:10.2196/67201 · Cited by 16
Lachance, O., Goyer, F., Adhikari, N. K. J., Masse, M.-H., Bilodeau, J., Lamontagne, F., & Leclair, M.-A. (2021) · Journal of Medical Case Reports · doi:10.1186/s13256-021-02869-4 · Cited by 11
“Another trial found that high-dose intravenous vitamin C reduced 28-day mortality in patients with sepsis and acute respiratory distress syndrome [3].”
BackgroundZarei, M., Rahimi, K., Hassanzadeh, K., Abdi, M., Hosseini, V., Fathi, A., & Kakaei, K. (2021) · Environmental Research · doi:10.1016/j.envres.2021.111555 · Cited by 11
Lee, M., Jung, S., Baek, M. S., Shin, J., & Kim, W. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11070610 · Cited by 12
“For example, the CITRIS-ALI trial revealed no significant difference in the SOFA score change at 96 h between the vitamin C and placebo groups [36].”
MethodVitamin C for Sepsis and Septic Shock
Ammar, M. A., Ammar, A. A., Condeni, M. S., & Bell, C. M. (2021) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000001423 · Cited by 12
Cao, J., Wang, Z. C., Wang, Y. L., et al. (2022) · BMC Urology · doi:10.1186/s12894-022-00988-8 · Cited by 11
“Studies have indicated that age is a risk factor for the progression to severe sepsis or septic shock [9].”
BackgroundRust, P., & Ekmekçioğlu, C. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20075400 · Cited by 17
“No unexpected adverse effects occurred [134].”
Sun, L., Zhao, J.-H., Fan, W.-Y., Feng, B., Liu, W., Chen, R.-Q., Ban, C., Dang, A.-G., Wang, M., Luo, K., et al. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad105 · Cited by 11
Lauer, A., Burkard, M., Niessner, H., Leischner, C., Renner, O., Vollbracht, C., Michels, H., Busch, C., Sinnberg, T. W., & Venturelli, S. (2021) · Nutrients · doi:10.3390/nu13072366 · Cited by 12
“published the CITRIS-ALI trial: In this preliminary study of patients with sepsis and ARDS, a 96-h infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury [57].”
MethodHemilä, H., & Chalker, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.659001 · Cited by 14
Cell-free DNA in sepsis: from molecular insights to clinical management
Li, L., Huang, H., He, Y., Pang, J., Xiao, S.-C., Xia, Z., & Zheng, Y. (2025) · Military Medical Research · doi:10.1186/s40779-025-00668-2 · Cited by 16
“However, recent large-scale multicenter randomized controlled trials have failed to confirm these clinical benefits, leading to ongoing debate regarding vitamin C’s effectiveness in sepsis management [376–378].”
Elajaili, H. B., Dee, N. M., Dikalov, S., Kao, J. P. Y., & Nozik‐Grayck, E. (2023) · Molecular Imaging and Biology · doi:10.1007/s11307-023-01826-5 · Cited by 11
Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial)
Anstey, M., Aljeaidi, M. S., Palmer, R. N., Jacques, A., Mevavala, B. V., Litton, E., & Wibrow, B. A. (2023) · Journal of Critical Care · doi:10.1016/j.jcrc.2023.154369 · Cited by 10
Ding, N., Zeng, Z., Luo, J., & Li, K. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1290749 · Cited by 11
Metadata
- Authors
- Fowler, A. A., Truwit, J. D., Hite, R. D., Morris, P. E., DeWilde, C., Priday, A., Fisher, B., Thacker, L. R., Natarajan, R., Brophy, D. F., Sculthorpe, R., Nanchal, R., Syed, A., Sturgill, J., Martin, G. S., Sevransky, J., Kashiouris, M., Hamman, S., Egan, K. F., Hastings, A., Spencer, W., Tench, S., Mehkri, O., Bindas, J., Duggal, A., Graf, J., Zellner, S., Yanny, L., McPolin, C., Hollrith, T., Kramer, D., Ojielo, C., Damm, T., Cassity, E., Wieliczko, A., & Halquist, M.
- Affiliations
- Virginia Commonwealth University (US)
- Froedtert Hospital (US)
- Cleveland Clinic (US)
- University of Kentucky (US)
- Emory University (US)
- Fairview Hospital, Cleveland, Ohio
- Aurora St. Luke's Medical Center (US)
- Corresponding author
- Fowler, Alpha A.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-10-01
- Volume
- 322
- Issue
- 13
- Pages
- 1261
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6777268
- OpenAlex
- W2977803759
- Cited by
- 836
- References
- 32
- Citations by year
- 2026: 56 · 2025: 81 · 2024: 68 · 2023: 105 · 2022: 134 · 2021: 181 · 2020: 198 · 2019: 12
- FWCI
- 99.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000058)
- National Heart, Lung, and Blood Institute (UM1HL116885)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR072000)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Keywords
- vitamin C, sepsis, acute respiratory distress syndrome, acute respiratory failure, organ failure, Sequential Organ Failure Assessment score, C-reactive protein, thrombomodulin, inflammatory markers, vascular injury, critically ill patients, length of hospital stay
- MeSH terms
- Adult, Aged, Ascorbic Acid, C-Reactive Protein, Double-Blind Method, Female, Humans, Infusions, Intravenous, Intensive Care Units, Male, Middle Aged, Multiple Organ Failure, Respiratory Distress Syndrome, Vitamins, Biomarkers, Thrombomodulin, Sepsis, Organ Dysfunction Scores
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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