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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Matthay, M. A., Aldrich, J. M., & Gotts, J. E. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30127-2 · Cited by 351
“11 Finally, ECMO should be considered using the inclusion and exclusion criteria of the EOLIA trial.”
MethodIntravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit
Lamontagne, F., Masse, M.-H., Menard, J., Sprague, S., Pinto, R., Heyland, D. K., Cook, D. J., Battista, M.-C., Day, A. G., Guyatt, G. H., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2200644 · Cited by 350
Oxidative Stress and Endothelial Dysfunction in Sepsis and Acute Inflammation
Joffre, J., & Hellman, J. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0027 · Cited by 368
The effects of sepsis on endothelium and clinical implications
Dolmatova, E. V., Wang, K., Mandavilli, R., & Griendling, K. K. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa070 · Cited by 324
“While in that study, the 28-day mortality was significantly lower in vitamin C group compared to the placebo group, the authors point out that per study design, mortality was a secondary outcome, and some internal biases could not be excluded.(160) Thus, large randomized multi-centre studies are still needed to establ…”
ResultSevransky, J., Rothman, R. E., Hager, D. N., Bernard, G. R., Brown, S. M., Buchman, T. G., Busse, L. W., Coopersmith, C. M., DeWilde, C., Ely, E. W., et al. (2021) · JAMA · doi:10.1001/jama.2020.24505 · Cited by 296
Self-citationShi, J., Yu, T.-Y., Song, K., Du, S., He, S.-M., Hu, X.-X., Li, X.-Y., Li, H., Dong, S., Zhang, Y., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101954 · Cited by 226
Critical care management of adults with community-acquired severe respiratory viral infection
Arabi, Y. M., Fowler, R., & Hayden, F. G. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05943-5 · Cited by 263
“However, mortality, which was one of the forty-six pre-specified secondary endpoints, was significantly lower with vitamin C [40].”
BackgroundThe Role of Vitamin C, Vitamin D, and Selenium in Immune System against COVID-19
Bae, M., & Kim, H. (2020) · Molecules · doi:10.3390/molecules25225346 · Cited by 269
“An intravenous treatment with high-dose vitamin C has shown beneficial effects on sepsis and septic shock [18,21].”
BackgroundMoskowitz, A., Huang, D. T., Hou, P. C., Gong, J., Doshi, P. B., Grossestreuer, A. V., Andersen, L. W., Ngo, L., Sherwin, R. L., Berg, K. M., et al. (2020) · JAMA · doi:10.1001/jama.2020.11946 · Cited by 253
The Role of Micronutrients in Support of the Immune Response against Viral Infections
Pecora, F., Persico, F., Argentiero, A., Neglia, C., & Esposito, S. (2020) · Nutrients · doi:10.3390/nu12103198 · Cited by 284
“Fowler AA 2019 [72] Adults RCT Vitamin C (IV 50 mg/kg every 6 h for 96 h) Significant reduction in 28-day all-cause mortality (p = 0.”
BackgroundPilot trial of high-dose vitamin C in critically ill COVID-19 patients
Zhang, J., Rao, X., Li, Y., Zhu, Y., Liu, F., Guo, G., Luo, G., Meng, Z., Backer, D. D., Xiang, H., et al. (2021) · Annals of Intensive Care · doi:10.1186/s13613-020-00792-3 · Cited by 258
Could Vitamins Help in the Fight Against COVID-19?
Jovic, T. H., Ali, S. R., Ibrahim, N., Jessop, Z. M., Tarassoli, S. P., Dobbs, T. D., Holford, P., Thornton, C. A., & Whitaker, I. S. (2020) · Nutrients · doi:10.3390/nu12092550 · Cited by 234
Egi, M., Ogura, H., Yatabe, T., Atagi, K., Inoue, S., Iba, T., Kakihana, Y., Kawasaki, T., Kushimoto, S., Kuroda, Y., et al. (2021) · Journal of Intensive Care · doi:10.1186/s40560-021-00555-7 · Cited by 232
Schönrich, G., Raftery, M. J., & Samstag, Y. (2020) · Advances in Biological Regulation · doi:10.1016/j.jbior.2020.100741 · Cited by 226
A new clinical trial to test high-dose vitamin C in patients with COVID-19
Carr, A. C. (2020) · Critical Care · doi:10.1186/s13054-020-02851-4 · Cited by 227
“A recently published RCT carried out in the USA in 167 patients with sepsis-related ARDS indicated that administration of ~ 15 g/day of IV vitamin C for 4 days may decrease mortality in these patients [3].”
BackgroundNutrition Therapy in Critically Ill Patients With Coronavirus Disease 2019
Martindale, R. G., Patel, J. J., Taylor, B. E., Arabi, Y. M., Warren, M. M., & McClave, S. A. (2020) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1930 · Cited by 228
Phenotypes and personalized medicine in the acute respiratory distress syndrome
Matthay, M. A., Arabi, Y. M., Siegel, E. R., Ware, L. B., Bos, L. D. J., Sinha, P., Beitler, J. R., Wick, K. D., Curley, M. A. Q., Constantin, J., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06296-9 · Cited by 219
The role of macrophages polarization in sepsis-induced acute lung injury
Wang, Z., & Wang, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1209438 · Cited by 235
Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review
Infusino, F., Marazzato, M., Mancone, M., Fedele, F., Mastroianni, C. M., Severino, P., Ceccarelli, G., Santinelli, L., Cavarretta, E., Marullo, A. G. M., et al. (2020) · Nutrients · doi:10.3390/nu12061718 · Cited by 205
Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19
Holford, P., Carr, A. C., Jovic, T. H., Ali, S. R., Whitaker, I. S., Marik, P. E., & Smith, A. D. (2020) · Nutrients · doi:10.3390/nu12123760 · Cited by 209
“Sepsis and ARDS (n = 167): IV vitamin C (4 day): X systemic organ failure score X C-reactive protein, thrombomodulin X ventilator-free days ↓ 28 day mortality ↑ ICU-free days ↑ hospital-free days [28] • Placebo (n = 83) 0 mg/kg bw/day”
BackgroundThe Emerging Role of Vitamin C as a Treatment for Sepsis
Kashiouris, M. G., L’Heureux, M., Cable, C. A., Fisher, B. J., Leichtle, S. W., & Fowler, A. A. (2020) · Nutrients · doi:10.3390/nu12020292 · Cited by 177
Self-citationLi, J., Deng, S., Li, J., Li, L., Zhang, F., Zou, Y., Wu, D., & Xu, Y. X. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-022-00318-8 · Cited by 183
“As these diseases are associated with the high morbidity and mortality rates in critically ill patients, they constitute a major public health burden; moreover, they have no effective patient-specific treatments [32, 33].”
BackgroundGalmés, S., Serra, F. A., & Palou, A. (2020) · Nutrients · doi:10.3390/nu12092738 · Cited by 179
Myth Busters: Dietary Supplements and COVID-19
Adams, K. K., Baker, W. L., & Sobieraj, D. M. (2020) · Annals of Pharmacotherapy · doi:10.1177/1060028020928052 · Cited by 174
The use of IV vitamin C for patients with COVID-19: a case series
Hiedra, R., Lo, K. B., Elbashabsheh, M., Gul, F., Wright, R. M., Albano, J., Azmaiparashvili, Z., & Patarroyo‐Aponte, G. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1794819 · Cited by 167
“Vitamin C together with corticosteroids and thiamine was found to be associated with reduced risk of progressive organ dysfunction, including acute kidney injury, and reduction in mortality in patients with severe sepsis and septic shock [10,11].”
BackgroundCerullo, G., Negro, M., Parimbelli, M., Pecoraro, M., Perna, S., Liguori, G., Rondanelli, M., Cena, H., & D’Antona, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.574029 · Cited by 179
Jamalimoghadamsiahkali, S., Zarezade, B., Koolaji, S., SeyedAlinaghi, S., Zendehdel, A., Tabarestani, M., Moghadam, E. S., Abbasian, L., Manshadi, S. A. D., Salehi, M., et al. (2021) · European journal of medical research · doi:10.1186/s40001-021-00490-1 · Cited by 160
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Overview of the possible role of vitamin C in management of COVID-19
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The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19
Carr, A. C., & Rowe, S. (2020) · Nutrients · doi:10.3390/nu12113286 · Cited by 155
Immunotherapy in sepsis - brake or accelerate?
Steinhagen, F., Schmidt, S. V., Schewe, J., Peukert, K., Klinman, D. M., & Bode, C. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107476 · Cited by 152
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“44 Clinical trials with large sample sizes conducted on ICU patients 15 36–38 reported few adverse events (AEs).”
InfluentialThe Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review
James, P. T., Ali, Z., Armitage, A. E., Bonell, A., Cerami, C., Drakesmith, H., Jobe, M., Jones, K. S., Liew, Z., Moore, S. E., et al. (2021) · The Journal of Nutrition · doi:10.1093/jn/nxab059 · Cited by 147
Curcumin (a constituent of turmeric): New treatment option against COVID‐19
Babaei, F., Nassiri‐Asl, M., & Hosseinzadeh, H. (2020) · Food Science & Nutrition · doi:10.1002/fsn3.1858 · Cited by 146
“Recently, rescue therapy with high-dose vitamin C has been suggested to use for these patients (Fowler et al., 2019).”
BackgroundPharmacological principles guiding prolonged glucocorticoid treatment in ARDS
Meduri, G. U., Annane, D., Confalonieri, M., Chrousos, G. P., Rochwerg, B. N., Busby, A. D., Ruaro, B., & Meibohm, B. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06289-8 · Cited by 144
“A recent RCT on patients with sepsis-associated ARDS reported a possible reduction in 28-day all-cause mortality, although as this was a secondary outcome, it was under-powered [64].”
Zhao, S., Chen, F., Yin, Q., Wang, D., Han, W., & Zhang, Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.571810 · Cited by 145
“Then, the environmental stimuli mediate triggering, thereby promoting NLRP3 inflammasome assembly, and then caspase-1 processes the immature preforms of cytokines to mature cytokines (IL-1β and IL-18) (Bauernfeind et al., 2011; Franchi and Nunez, 2012).”
BackgroundCombined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock
Chang, P., Liao, Y., Guan, J., Guo, Y., Zhao, M. F., Hu, J., Zhou, J., Wang, H., Cen, Z., Tang, Y., et al. (2020) · CHEST Journal · doi:10.1016/j.chest.2020.02.065 · Cited by 141
Lin, Y., Xu, Y., & Zhang, Z. (2020) · Inflammation · doi:10.1007/s10753-020-01233-w · Cited by 136
“[130] Moreover, a recent multicenter, open-label RCT conducted in 216 patients with septic shock recruited from 10 ICUs demonstrated that combination therapy with vitamin C (1.”
BackgroundHemilä, H., & Chalker, E. (2020) · Journal of Intensive Care · doi:10.1186/s40560-020-0432-y · Cited by 130
“We did not include two further trials that reported “ventilator-free days” since we were unable to convert this to our outcome of interest, “duration of mechanical ventilation” [20, 21].”
BackgroundDietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment
Lordan, R., Rando, H. M., & Greene, C. S. (2021) · mSystems · doi:10.1128/msystems.00122-21 · Cited by 137
Ma, W., Tang, S., Yao, P., Zhou, T., Niu, Q., Liu, P.-F., Tang, S., Chen, Y., Gan, L., & Cao, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02127-9 · Cited by 149
Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021
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Self-citationVitamin C in the Treatment of COVID-19
Milani, G. P., Macchi, M., & Guz‐Mark, A. (2021) · Nutrients · doi:10.3390/nu13041172 · Cited by 122
Kaye, K. O., Paprottka, F. J., Escudero, R., Casabona, G., Montes, J., Fakin, R. M., Moke, L., Stasch, T., Richter, D. F., & Benito-Ruiz, J. (2020) · Aesthetic Plastic Surgery · doi:10.1007/s00266-020-01752-9 · Cited by 118
Targeting the host response in sepsis: current approaches and future evidence
Bode, C., Weis, S., Sauer, A., Wendel‐Garcia, P. D., & David, S. (2023) · Critical Care · doi:10.1186/s13054-023-04762-6 · Cited by 127
Nutrition in the Intensive Care Unit—A Narrative Review
Hill, A., Elke, G., & Weimann, A. (2021) · Nutrients · doi:10.3390/nu13082851 · Cited by 131
Kontoghiorghes, G. J., Kolnagou, A., Kontoghiorghe, C., Mourouzidis, L., Timoshnikov, V. A., & Polyakov, N. E. (2020) · Medicines · doi:10.3390/medicines7080045 · Cited by 116
Yealy, D. M., Mohr, N. M., Shapiro, N. I., Venkatesh, A. K., Jones, A. E., & Self, W. H. (2021) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2021.02.006 · Cited by 123
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Acute Respiratory Distress Syndrome
Williams, G. W., Berg, N. K., Reskallah, A., Yuan, X., & Eltzschig, H. K. (2020) · Anesthesiology · doi:10.1097/aln.0000000000003571 · Cited by 123
Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19?
Feyaerts, A. F., & Luyten, W. H. M. L. (2020) · Nutrition · doi:10.1016/j.nut.2020.110948 · Cited by 110
Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy
Pisoschi, A. M., Pop, A., Iordache, F., Stanca, L., Geicu, O. I., Bîlteanu, L., & Șerban, A. I. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114175 · Cited by 118
Spices and herbs: Potential antiviral preventives and immunity boosters during COVID ‐19
Singh, N. A., Kumar, P., Jyoti, J., & Kumar, N. G. (2021) · Phytotherapy Research · doi:10.1002/ptr.7019 · Cited by 112
Chen, L., Huang, Q., Zhao, T., Sui, L., Wang, S., Xiao, Z., Nan, Y., & Ai, K. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102046 · Cited by 99
“Current therapies for treating sepsis are dominated by anti-inflammatory drugs, such as melatonin [ [16]], and traditional antioxidants, such as vitamin C [17] and N-acetylcysteine [18].”
Timoshnikov, V. A., Selyutina, O. Y., Polyakov, N. E., Didichenko, V., & Kontoghiorghes, G. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031247 · Cited by 99
Aytür, Y. K. (2020) · Turkish Journal of Physical Medicine and Rehabilitation · doi:10.5606/tftrd.2020.6444 · Cited by 98
“adequate fluid intake, and supportive measures (daily intake of 2 g/kg protein, vitamin C, zinc, selenium and high fiber content in the diet) should be taken.[45-50]”
BackgroundGastrointestinal symptoms, pathophysiology, and treatment in COVID-19
Zhang, J., Garrett, S., & Sun, J. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.08.013 · Cited by 100
Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)
Huang, Q., Le, Y., Li, S., & Bian, Y. (2024) · Respiratory Research · doi:10.1186/s12931-024-02678-5 · Cited by 119
Psychopharmacology of COVID-19
Bilbul, M., Paparone, P., Kim, A. M., Mutalik, S. P., & Ernst, C. L. (2020) · Psychosomatics · doi:10.1016/j.psym.2020.05.006 · Cited by 97
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Emerging pharmacological therapies for ARDS: COVID-19 and beyond
Horie, S., McNicholas, B., Rezoagli, E., Pham, T. O., Curley, G., McAuley, D. F., O’Kane, C. M., Nichol, A., dos Santos, C. C., Rocco, P. R. M., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06141-z · Cited by 100
“The time delay between onset of shock and development of ARDS delayed the administration of Vitamin C infusion when compared to other studies in sepsis [6].”
BackgroundResultThe role of ferroptosis in acute lung injury
Liu, X., Zhang, J., & Xie, W. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04327-7 · Cited by 93
Sepsis, a 2020 review for the internist
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Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection
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“A study of 167 patients with sepsis and ARDS suggested that mortality and intensive care unit stay were significantly reduced in the high-dose vitamin C group [28].”
BackgroundChallenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies
Battaglini, D., Fazzini, B., Silva, P. L., Cruz, F. F., Ball, L., Robba, C., Rocco, P. R. M., & Pelosi, P. P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12041381 · Cited by 93
Vasopressor Therapy in the Intensive Care Unit
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Recent advances in the understanding and management of ARDS
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“Previously vitamin C has been shown to reduce mortality, vasopressor usage and organ failure in sepsis patients [9,10], however, larger randomized trials failed to show any major health benefits [11,12].”
The Role of Vitamin C as Adjuvant Therapy in COVID-19
Kumari, P., Dembra, S., Dembra, P., Bhawna, F., Gul, A., Ali, B., Sohail, H., Kumar, B., Memon, M. K., & Rizwan, A. (2020) · Cureus · doi:10.7759/cureus.11779 · Cited by 84
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The pathogenesis and potential therapeutic targets in sepsis
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Harm of IV High-Dose Vitamin C Therapy in Adult Patients: A Scoping Review
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“In the CITRIS-ALI trial, an intravenous administration of vitamin C was recommended to reduce mortality [44].”
Micronutrients in critically ill patients with severe acute kidney injury – a prospective study
Ostermann, M., Summers, J. A., Lei, K., Card, D. J., Harrington, D. J., Sherwood, R. A., Turner, C., Dalton, N. R., Peacock, J. L., & Bear, D. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-58115-2 · Cited by 76
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“23”
Vasopressor and Inotrope Therapy in Cardiac Critical Care
Jentzer, J. C., & Hollenberg, S. M. (2020) · Journal of Intensive Care Medicine · doi:10.1177/0885066620917630 · Cited by 77
Meduri, G. U., & Chrousos, G. P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00161 · Cited by 80
“(secondary outcome) (284) .”
Effective Immune Functions of Micronutrients against SARS-CoV-2
Junaid, K., Ejaz, H., Abdalla, A. E., Abosalif, K. O. A., Ullah, M. I., Yasmeen, H., Younas, S., Hamam, S. S. M., & Rehman, A. (2020) · Nutrients · doi:10.3390/nu12102992 · Cited by 71
Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C
Lankadeva, Y. R., Peiris, R. M., Okazaki, N., Birchall, I. E., Trask-Marino, A. L., Dornom, A., Vale, T. A. M., Evans, R. G., Yanase, F., Bellomo, R., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004770 · Cited by 72
“5 g, every 6 hr for 96 hr) showed a numerical reduction in 28-day mortality (11).”
BackgroundPromises and challenges of personalized medicine to guide ARDS therapy
Wick, K. D., McAuley, D. F., Levitt, J. E., Beitler, J. R., Annane, D., Riviello, E. D., Calfee, C. S., & Matthay, M. A. (2021) · Critical Care · doi:10.1186/s13054-021-03822-z · Cited by 73
“03), significantly more ICU-free days, and numerically more ventilator-free days [38].”
BackgroundMethod
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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