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
Cites
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“For sepsis and severe acute respiratory failure, the CITRIS-ALI trial investigated the use of intravenous vitamin C and found decreased mortality during the four-day administration of vitamin C [82,83].”
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Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock
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Was ist gesichert in der Therapie der Sepsis?
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“However, these findings were in a planned secondary analysis, and the primary end point of change in organ failure was not significantly different between the two groups (6).”
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“The CITRUS-ALI trial compared a four-day course of IV ascorbic acid at a higher dose (200 mg/kg/day or ~ 14 g/day in a 70 kg adult) with placebo in 167 patients with sepsis and severe respiratory failure (Acute Respiratory Distress Syndrome, ARDS) [9].”
Early high-dose vitamin C for out-of-hospital cardiac arrest: the VITaCCA randomized clinical trial
Rozemeijer, S., Dubois, E. A., de Grooth, H., den Uil, C. A., Rettig, T. C. D., Rijpstra, T. A., van den Bogaard, B., van Zanten, Bosman, R. J., Elbers, P., et al. (2026) · Intensive Care Medicine · doi:10.1007/s00134-026-08492-5 · Cited by 5
“We chose 10 g vitamin C as a pharmacological regimen since this leads to supraphysiological plasma concentrations [5], and since it is between the 6 g and 16 g doses used in previous studies [20, 24–28].”
Vitamin C for patients with sepsis?
Hemilä, H., & Chalker, E. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1450091 · Cited by 4
Herbal and Dietary Supplements as Adjunctive Treatment for Mild SARS-CoV-2 Infection in Italy
Licata, A., Seidita, A., Como, S., Carlo, G. D., Cammilleri, M., Bonica, R., Soresi, M., Veronese, N., Chianetta, R., Citarrella, R., et al. (2025) · Nutrients · doi:10.3390/nu17020230 · Cited by 6
Prasad, N., Grossestreuer, A. V., Meyer, N. J., Perman, S. M., Mikkelsen, M. E., Hollander, J. E., & Gaieski, D. F. (2021) · Scientific Reports · doi:10.1038/s41598-021-94473-1 · Cited by 4
A Nomogram for Predicting the Mortality of Patients with Acute Respiratory Distress Syndrome
Wang, Z., Xing, L., Cui, H., et al. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/5940900 · Cited by 4
Qin, M., Xu, K., Chen, Z., Wen, X., Tang, Y., Gao, Y., Zhang, H., & Ma, X. (2024) · Nutrition Reviews · doi:10.1093/nutrit/nuae154 · Cited by 4
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A detailed examination of coronavirus disease 2019 (COVID-19): Covering past and future perspectives
Yasmin, S., & Ansari, M. Y. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.107398 · Cited by 6
Zhang, F., Wang, J., Wang, W., Chen, G., Tang, H., & Zhai, X. (2025) · Journal of International Medical Research · doi:10.1177/03000605251340338 · Cited by 5
“32 Ferroptosis promotes ALI development following infections.”
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Wang, X., Yin, D., Sun, J., Zhang, L., Ye, Y., & Guo, Q. (2025) · Inflammation · doi:10.1007/s10753-025-02321-5 · Cited by 4
Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?
Marik, P. E., Varón, J., & Surani, S. (2020) · World Journal of Diabetes · doi:10.4239/wjd.v11.i4.90 · Cited by 5
Zheng, F. (2022) · Pakistan Journal of Medical Sciences · doi:10.12669/pjms.38.3.4758 · Cited by 4
A comprehensive nutritional support perspective in patients with COVID-19: a review
Ebrahimpour‐Koujan, S., Sohrabpour, A. A., Safari, S., Baziar, N., Hadavi, S., Payahoo, L., & Shabani, S. (2022) · Nutrition & Food Science · doi:10.1108/nfs-01-2022-0015 · Cited by 4
Current Practice Review in the Management of Acute Respiratory Distress Syndrome
Chudow, M. B., Condeni, M. S., Dhar, S., Heavner, M. S., Nei, A. M., & Bissell, B. D. (2022) · Journal of Pharmacy Practice · doi:10.1177/08971900221108713 · Cited by 4
HAT therapy for sepsis: A review of the therapeutic rationale and current clinical evaluation status
Sun, Y., Yang, Y., Ye, Z., & Sun, T. (2023) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2023.04.003 · Cited by 5
The critical care literature 2022
Winters, M. E., Hu, K. M., Martinez, J. P., Mallemat, H. A., & Brady, W. J. (2024) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2024.03.028 · Cited by 4
Corrao, S., Raspanti, M., Agugliaro, F., Gervasi, F., Bernardo, F. D., Natoli, G., & Argano, C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13133987 · Cited by 6
“Various clinical studies evaluating high-dose intravenous vitamin C administration in patients with severe sepsis, acute lung injury, and acute respiratory distress syndrome admitted to intensive care units have shown mixed results regarding laboratory and clinical outcomes [30–32].”
BackgroundResultAging and Coronavirus: Exploring Complementary Therapies to Avoid Inflammatory Overload
Neto, L. D. O., Tavares, V. D. D. O., Coelho, N. L. G., Schuch, F. B., & de Lima, K. C. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00354 · Cited by 4
COVID-19 Hastalarında Yoğun Bakım Yaklaşımı
Ayoğlu, H. (2020) · Turkish Journal of Diabetes and Obesity · doi:10.25048/tudod.767999 · Cited by 4
Vitamin C biochemistry: From scurvy to COVID-19 treatment
Zakić, T., Soskic, M. B., Kalezic, A., Korać, A., Janković, A., & Korać, B. (2020) · Hrana i ishrana · doi:10.5937/hraish2002059z · Cited by 4
“The CITRIS-ALI Randomized Clinical Trial [147] has shown that HD-IVC can successfully reduce mortality and ICU stay in patients with sepsis and ARDS.”
MethodFooled by Significance Testing: An Analysis of the LOVIT Vitamin C Trial
Sidebotham, D. A. (2022) · Journal of ExtraCorporeal Technology · doi:10.1051/ject/202254324 · Cited by 6
Turkia, M. (2020) · Cureus · doi:10.7759/cureus.12403 · Cited by 4
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Protective effect and mechanism of Sufentanil on acute lung injury in septic mice
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Ow, C. P. C., Peiris, R. M., Trask-Marino, A. L., Hood, S. G., Betrie, A. H., Lane, D. J. R., Bellomo, R., Plummer, M. P., May, C. N., & Lankadeva, Y. R. (2025) · Critical Care · doi:10.1186/s13054-025-05799-5 · Cited by 3
Polydatin attenuates LPS-induced acute lung injury in rats via targeting HSP90AB1
Han, L., Shi, Z., Meng, F., Han, Y., Li, X., Zhang, X., Xu, J., & Zhang, T. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121390 · Cited by 3
Rowe, S., Collins, P. D., Stacey, S., & Carr, A. C. (2021) · British Journal of Hospital Medicine · doi:10.12968/hmed.2020.0730 · Cited by 3
Adjunctive Therapies in Acute Respiratory Distress Syndrome
Trieu, M., & Qadir, N. (2023) · Critical Care Clinics · doi:10.1016/j.ccc.2023.12.004 · Cited by 5
New randomized controlled trials on micronutrients in critical care nutrition: A narrative review
Halim, Z., Huang, Y., Lee, Z., & Lew, C. C. H. (2024) · Nutrition in Clinical Practice · doi:10.1002/ncp.11195 · Cited by 7
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Ferrostatin-1 mitigates acute lung injury by reducing ferroptosis levels in gas explosions
Zhang, H., Tian, L., Wang, P., et al. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.102773 · Cited by 3
Vitamin C Versus Placebo in Pediatric Septic Shock (VITACiPS) - A Randomised Controlled Trial
Sankar, J., Manoharan, A., Lodha, R., Sharma, H. P., & Kabra, S. (2025) · Journal of Intensive Care Medicine · doi:10.1177/08850666251362121 · Cited by 3
Han, R., Tian, N., Sun, Z.-G., et al. (2025) · Journal of Surgical Research · doi:10.1016/j.jss.2025.07.009 · Cited by 3
Farzanegan, B., Shafigh, N., Hasheminik, M., Alipour, H., Behzadfar, A., Safaee, N., Shafigh, E., & Dizaji, M. K. (2025) · BMC Infectious Diseases · doi:10.1186/s12879-025-11831-4 · Cited by 4
“…were not measured among the patients who “graduated” early from the ICU (a group that was heavily shifted towards the HDIVC group) or in those patients who died (heavily shifted towards the placebo group), indicating a strong selection bias, which makes these results difficult to interpret [27].”
Mesenchymal stem cells in sepsis-induced organ dysfunction: mechanisms and therapeutic potential
Yang, T., Xu, X., An, J., Li, B., & Dou, Z. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04752-1 · Cited by 4
Limitations in the Design of Critical Care Studies and Suggestions for Future Research Directions
Meduri, G. U., Lanini, S., & Smit, J. M. (2026) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/a-2762-8278 · Cited by 3
Guinhut, M., Melchior, J., Godart, N. T., & Hanachi, M. (2020) · International Journal of Clinical Medicine · doi:10.4236/ijcm.2020.1112056 · Cited by 3
Potential benefit of high-dose intravenous vitamin C for coronavirus disease 2019 pneumonia
Zhao, B., Li, M., Ling, Y., et al. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001746 · Cited by 3
Can Nutritional Supports Beneficial in Other Viral Diseases Be Favorable for COVID-19?
Zelka, F. Z., Kocatürk, R. R., Özcan, Ö. Ö., & Karahan, M. (2022) · Korean Journal of Family Medicine · doi:10.4082/kjfm.20.0134 · Cited by 3
Chemistry and Biomedical Applications of Cumin and Turmeric: A Review, Challenge and Perspective
Mitra, A. K. (2022) · Chemistry Africa · doi:10.1007/s42250-022-00410-8 · Cited by 3
Potential nutritional and pharmacological treatment of glycocalyx alterations during sepsis
Pergolizzi, C., Franchi, F., Taccone, F. S., Preiser, J., & Scolletta, S. (2023) · Minerva Anestesiologica · doi:10.23736/s0375-9393.22.16834-3 · Cited by 3
The Increased Risk of Renal Stones in Patients With COVID-19 Infection
Kasiri, H., Moradimajd, P., Samaee, H., & Ghazaeian, M. (2022) · Pharmaceutical and Biomedical Research · doi:10.32598/pbr.8.4.898.6 · Cited by 3
Trimester-specific reference intervals of hemostasis biomarkers for healthy pregnancy
Haijun, X., Yu, W., Li, L., et al. (2023) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2023.2233903 · Cited by 3
Intravenous vitamin C against acute respiratory distress syndrome: A narrative review
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Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit
Chiscano‐Camón, L., Ruiz‐Rodríguez, J. C., Plata-Menchaca, E. P., Martin, L., Bajaña, I., Martin-Rodríguez, C., Palmada, C., Ferrer, R., Camós, S., Villena-Ortiz, Y., et al. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1301001 · Cited by 4
Early, very high-dose, and prolonged vitamin C administration in murine sepsis
Kim, O., Kim, T. W., Kang, H., Jeon, T. J., Chang, E. S., Lee, H. J., & Kim, W. (2025) · Scientific Reports · doi:10.1038/s41598-025-02622-7 · Cited by 4
Evolution of Clinical Trials in Anticoagulation for Sepsis: Bridging Past to Future
Iba, T., Helms, J., Maier, C. L., et al. (2025) · Seminars in Thrombosis and Hemostasis · doi:10.1055/a-2657-6380 · Cited by 3
Briegel, J. (2019) · Der Anaesthesist · doi:10.1007/s00101-019-00705-5 · Cited by 3
COVID-19 Perfect Storm (Part II): Role of Vitamins as Therapy or Preventive Strategy in Aged People
Fiorino, S., Gallo, C. G., Zippi, M., Sabbatani, S., Manfredi, R., Moretti, R., Fogacci, E., Maggioli, C., Loffredo, F. T., Giampieri, E., et al. (2020) · Cited by 3
The promise and pitfalls of composite endpoints in sepsis and COVID ‐19 clinical trials
Brown, P. M., Rogne, T., & Solligård, E. (2020) · Pharmaceutical Statistics · doi:10.1002/pst.2070 · Cited by 3
Surgical Infection Society Research Priorities: A Narrative Review of Fourteen Years of Progress
Mele, T. S., Kaafarani, H. M. A., Guidry, C. A., Loor, M. M., Machado-Aranda, D., Mendoza, A. E., Morris‐Stiff, G. J., Rattan, R., Schubl, S. D., & Barie, P. S. (2020) · Surgical Infections · doi:10.1089/sur.2020.309 · Cited by 4
The Effect of High Dose Vitamin C (ascorbic acid) on Proinflammatory Cytokines in COVID-19
-, M. A. M. C. D. (2021) · Medical and Health Science Journal · doi:10.33086/mhsj.v5i1.1884 · Cited by 3
The use of vitamin C in the intensive care unit during the COVID-19 pandemic
Özgünay, Ş. E., Ceylan, İ., Ökmen, K., Sayan, H. E., Eminoğlu, Ş., Karasu, D., & Yavuz, Ş. (2021) · The European Research Journal · doi:10.18621/eurj.938778 · Cited by 3
“vitamin C every 6 hours did not change the sequential organ failure assessment (SOFA) score, the levels of inflammatory and vascular damage markers such as CRP and thrombomodulin but reduced the incidence of the 28day mortality and the days without ventilator use [29].”
BackgroundPotential Roles of Vitamins in the Management of COVID-19: A Comprehensive Review
Rezaei, H., Khiali, S., Rezaee, H., Baghi, H. B., Pourghasem, M., & Entezari‐Maleki, T. (2021) · Pharmaceutical Sciences · doi:10.34172/ps.2021.41 · Cited by 3
Major Publications in the Critical Care Pharmacotherapy Literature: 2021
Wieruszewski, P. M., Brickett, L. M., Dayal, L., Egan, A. M., Khanna, A. K., Lemieux, S. M., Mukkera, S. R., Patel, J. S., Reichert, M., Reynolds, T. R., et al. (2022) · Critical Care Explorations · doi:10.1097/cce.0000000000000823 · Cited by 3
“This systematic review and meta-analysis evaluated the effect of prokinetic regimens on feeding intolerance using a gastric residual volume (GRV) threshold of greater than or equal to 500 mL (52).”
MethodPrise en charge nutritionnelle des patients de réanimation ayant une infection au SARS-CoV-2
Pardo, E. (2020) · Le Praticien en Anesthésie Réanimation · doi:10.1016/j.pratan.2020.07.002 · Cited by 3
Medeiros, P. M. C., Schjalm, C., Christiansen, D., Sokolova, M., Pischke, S. E., Würzner, R., Mollnes, T. E., & Barratt‐Due, A. (2021) · Shock · doi:10.1097/shk.0000000000001834 · Cited by 4
Lines of Treatment of COVID-19 Infection
ElGoly, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-90595-4.00002-9 · Cited by 3
Current strategies in diagnostics and therapeutics against novel coronavirus disease (COVID-19)
ALOTAIBI, F. (2021) · Acta Pharmaceutica · doi:10.2478/acph-2022-0014 · Cited by 3
Møller, M. H., Shankar‐Hari, M., & Alhazzani, W. A. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202005-1984ed · Cited by 3
“This is further supported by the recently published CITRIS-ALI (Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis and Severe Acute Respiratory Failure) and VITAMINS (Effect of Vitamin C, Hydrocortisone, and Thiamine versus Hydrocortisone Alone on T…”
ResultVitamin C for the common cold and pneumonia
Hemilä, H., & Chalker, E. (2025) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.16926 · Cited by 20
The vitamin C paradigm: new frontiers in blood transfusion
Obeagu, E. I. (2025) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000003018 · Cited by 4
“Several clinical trials and studies have indicated that vitamin C can reduce mortality rates in patients receiving blood transfusions [ 40 , 41 ] .”
Perioperative Oxidative Stress and Sepsis: Pathophysiological and Clinical Implications
Drăgoescu, A. N., Pădureanu, V., Stănculescu, A. D., Andrei, M., Radu, M., Pădureanu, R., Iliescu, D. G., & Drăgoescu, P. O. (2025) · Cureus · doi:10.7759/cureus.94719 · Cited by 2
Vitamin C for sepsis: from mechanisms to individualized therapy
Xiao, Y., Gong, F., Zhang, L., & Gui, C. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1700351 · Cited by 2
Trends in Use of IV Vitamin C Among Patients With Sepsis
Segall, R. E., Lamontagne, F., Vail, E. A., Wunsch, H., Bosch, N. A., Walkey, A. J., Pinto, R. L., Gershengorn, H. B., & Adhikari, N. K. J. (2025) · Critical Care Medicine · doi:10.1097/ccm.0000000000007003 · Cited by 2
Chang, W.-H., Hu, T.-Y., & Kuo, L. (2026) · Diagnostics · doi:10.3390/diagnostics16010173 · Cited by 2
“…supportive strategies, including intravenous fluid strategies [30], choice of resuscitation targets (e.g., peripheral perfusion-based approaches versus lactate-driven strategies) [31], corticosteroid regimens [32,33], and vitamin C–based interventions with mixed findings across studies [34–36].”
Osier, W., Nozik‐Grayck, E., & Sul, C. (2026) · Antioxidants · doi:10.3390/antiox15020249 · Cited by 3
“Non-specific antioxidant treatments, including N-acetylcysteine and vitamin C, did not improve outcomes in ARDS [187–189].”
HDAC1 modulates sepsis-induced immunosuppression by driving the exhaustion of CD8+ T cells
Liu, D., Fan, J.-B., Wang, R., Li, Y., Bi, W.-D., Huang, S.-Y., Nie, H.-H., Feng, X.-F., Zhang, H.-C., Du, J., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.197224 · Cited by 3
Hu, S. L., Wang, Y., Zhou, W., Zhu, L., Chen, Y., Li, Q., Lv, X., & Yang, H. (2026) · Respiratory Research · doi:10.1186/s12931-026-03564-y · Cited by 2
Acute Kidney Allograft Injury Following Vitamin C Administration for Septic Shock
Mahling, M., Köppen, M., Mühlbacher, T., Amann, K., Königsrainer, A., Heyne, N., Haeberle, H. A., Nadalin, S., & Guthoff, M. (2020) · Kidney International Reports · doi:10.1016/j.ekir.2020.08.033 · Cited by 3
Huang, Y., Wang, W., Tang, Y., & Yue, S. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa330 · Cited by 2
“A recently published randomized controlled trial (RCT) carried out in the USA in 167 patients with sepsis related ARDS indicated that administration of ∼15 g/day of intravenous VC for 4 days may decrease mortality [13].”
BackgroundPlasma Ascorbic Acid Levels in Critically Ill Pediatric Patients
Choi, D. H., Basu, S., Levine, M., & Steinhorn, D. M. (2022) · Journal of Pediatric Intensive Care · doi:10.1055/s-0041-1741401 · Cited by 3
Montero, V. R., Ribes, C. M., Montell, M. P., & Zaragoza, R. (2022) · Medicina Intensiva · doi:10.1016/j.medin.2022.03.005 · Cited by 3
Micronutrients- The crucial dietary elements in Covid-19 pandemic: A review
Kumar, S., Moodithaya, S. S., Adithi, K., & Chatterjee, P. K. (2022) · Biomedicine · doi:10.51248/.v42i5.1967 · Cited by 2
Li, Z., Zhang, X., Wu, Y., Xie, C., Liu, C., He, X., Wu, Z., Hua, G., & Li, Y. (2023) · Emergency and Critical Care Medicine · doi:10.1097/ec9.0000000000000072 · Cited by 4
Recommendations and guidelines of integrative medicine for COVID-19 care: The APEC project outcome
Jia, L., Beidelschies, M. A., Evans, J. M., Niemtzow, R. C., Niemtzow, S. Z., Dusek, J. A., Lin, Y., Wu, C. G., Wang, C.-H. J., Su, Y., et al. (2024) · Integrative Medicine Research · doi:10.1016/j.imr.2024.101022 · Cited by 2
Hu, J., Zhang, J., Li, D., Hu, X. Y., Li, Q., Wang, W., Su, J., Wu, D., Kang, H., & Zhou, F. (2024) · Scientific Reports · doi:10.1038/s41598-024-54826-y · Cited by 3
Simmons, G. L., Sabo, R., Qayyum, R., Aziz, M., Martin, E., Bernard, R. J., Sriparna, M., McIntire, C. A., Krieger, E., Brophy, D. F., et al. (2024) · eJHaem · doi:10.1002/jha2.995 · Cited by 2
“Ascorbic acid (vitamin C) is an antioxidant/anti-inflammatory agent with the ability to inhibit NF-κ B-driven inflammatory cytokine (IL-6, IL-8, and TNF-α ) expression and to attenuateendothelialpermeability[5,6,7].”
BackgroundSelf-citationFeng, Q., Lv, Z., Ba, C., & Zhang, Y. Q. (2024) · Scientific Reports · doi:10.1038/s41598-024-74294-8 · Cited by 2
Moustafa, H. A. M., Elbery, F. H., Meslamani, A. Z. A., Okda, S. M., Alsfouk, B. A. A., & Kassem, A. B. (2025) · Pharmaceuticals · doi:10.3390/ph18030412 · Cited by 2
“However, another trial reported that a high dose of ascorbic acid in individuals with early sepsis and ARDS did not affect the organ failure assessment score at 96 h, but significantly reduced the 28-day all-cause mortality [88].”
Early Pharmaceutical Treatment Modalities for COVID-19 Patients in the Beginning of the Pandemic
Shareef, R. H., Sharba, Z. F., Muhammad-Baqir, B. M., & Mahbuba, W. A. (2025) · Medical Journal of Babylon · doi:10.4103/mjbl.mjbl_845_23 · Cited by 2
Cui, N., Yang, H., Chen, S., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117062 · Cited by 2
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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