{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:32:44Z","timestamp":1780068764712,"version":"3.54.0"},"reference-count":134,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1038\/s41390-021-01673-6","type":"journal-article","created":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T20:02:48Z","timestamp":1627761768000},"page":"328-336","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Vitamin therapy in sepsis"],"prefix":"10.1038","volume":"91","author":[{"given":"Eric L.","family":"Wald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Badke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren K.","family":"Hintz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spewak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7434-6747","authenticated-orcid":false,"given":"L. Nelson","family":"Sanchez-Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"1673_CR1","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1001\/jamapediatrics.2018.4839","volume":"173","author":"B Tan","year":"2019","unstructured":"Tan, B. et al. Global case-fatality rates in pediatric severe sepsis and septic shock: a systematic review and meta-analysis. JAMA Pediatr. 173, 352\u2013362 (2019).","journal-title":"JAMA Pediatr."},{"key":"1673_CR2","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1177\/0310057X0903700215","volume":"37","author":"T Corcoran","year":"2009","unstructured":"Corcoran, T., O\u2019Neill, M., Webb, S. & Ho, K. Prevalence of vitamin deficiencies on admission: relationship to hospital mortality in critically ill patients. Anaesth. Intens. Care 37, 254\u2013260 (2009).","journal-title":"Anaesth. Intens. Care"},{"key":"1673_CR3","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1097\/MPG.0000000000002688","volume":"70","author":"K Gerasimidis","year":"2020","unstructured":"Gerasimidis, K. et al. Assessment and interpretation of vitamin and trace element status in sick children: a position paper from the European Society for Paediatric Gastroenterology Hepatology, and Nutrition Committee on Nutrition. J. Pediatr. Gastroenterol. Nutr. 70, 873\u2013881 (2020).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"1673_CR4","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1097\/CCM.0000000000001572","volume":"44","author":"MW Donnino","year":"2016","unstructured":"Donnino, M. W. et al. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot Study. Crit. Care Med. 44, 360\u2013367 (2016).","journal-title":"Crit. Care Med."},{"key":"1673_CR5","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1001\/jama.2019.11825","volume":"322","author":"AA Fowler 3rd","year":"2019","unstructured":"Fowler, A. A. 3rd et al. 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. JAMA 322, 1261\u20131270 (2019).","journal-title":"JAMA"},{"key":"1673_CR6","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1164\/rccm.201908-1543LE","volume":"201","author":"EL Wald","year":"2020","unstructured":"Wald, E. L. et al. Hydrocortisone-ascorbic acid-thiamine use associated with lower mortality in pediatric septic shock. Am. J. Respir. Crit. Care Med. 201, 863\u2013867 (2020).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1673_CR7","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/s41430-018-0249-0","volume":"73","author":"Y Wang","year":"2019","unstructured":"Wang, Y., Shi, C., Yang, Z., Chen, F. & Gao, L. Vitamin D deficiency and clinical outcomes related to septic shock in children with critical illness: a systematic review. Eur. J. Clin. Nutr. 73, 1095\u20131101 (2019).","journal-title":"Eur. J. Clin. Nutr."},{"key":"1673_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1742-4658.2006.05607.x","volume":"274","author":"CL Linster","year":"2007","unstructured":"Linster, C. L. & Van Schaftingen, E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 274, 1\u201322 (2007).","journal-title":"FEBS J."},{"key":"1673_CR9","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1097\/00003246-199603000-00006","volume":"24","author":"E Borrelli","year":"1996","unstructured":"Borrelli, E. et al. Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Crit. Care Med. 24, 392\u2013397 (1996).","journal-title":"Crit. Care Med."},{"key":"1673_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-1131-2","volume":"19","author":"AC Carr","year":"2015","unstructured":"Carr, A. C., Shaw, G. M., Fowler, A. A. & Natarajan, R. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock? Crit. Care 19, 418 (2015).","journal-title":"Crit. Care"},{"key":"1673_CR11","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1089\/ars.2013.5401","volume":"19","author":"JX Wilson","year":"2013","unstructured":"Wilson, J. X. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid. Redox Signal. 19, 2129\u20132140 (2013).","journal-title":"Antioxid. Redox Signal."},{"key":"1673_CR12","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/biof.7","volume":"35","author":"JX Wilson","year":"2009","unstructured":"Wilson, J. X. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. BioFactors 35, 5\u201313 (2009).","journal-title":"BioFactors"},{"key":"1673_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0460-x","volume":"18","author":"HM Oudemans-van Straaten","year":"2014","unstructured":"Oudemans-van Straaten, H. M., Spoelstra-de Man, A. M. & de Waard, M. C. Vitamin C revisited. Crit. Care 18, 460 (2014).","journal-title":"Crit. Care"},{"key":"1673_CR14","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1089\/ars.2013.5205","volume":"19","author":"JM May","year":"2013","unstructured":"May, J. M. & Harrison, F. E. Role of vitamin C in the function of the vascular endothelium. Antioxid. Redox Signal. 19, 2068\u20132083 (2013).","journal-title":"Antioxid. Redox Signal."},{"key":"1673_CR15","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.chest.2017.07.014","volume":"152","author":"N Barabutis","year":"2017","unstructured":"Barabutis, N., Khangoora, V., Marik, P. E. & Catravas, J. D. Hydrocortisone and ascorbic acid synergistically prevent and repair lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. Chest 152, 954\u2013962 (2017).","journal-title":"Chest"},{"key":"1673_CR16","doi-asserted-by":"publisher","first-page":"L20","DOI":"10.1152\/ajplung.00300.2011","volume":"303","author":"BJ Fisher","year":"2012","unstructured":"Fisher, B. J. et al. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am. J. Physiol. Lung Cell Mol. Physiol. 303, L20\u201332 (2012).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"1673_CR17","doi-asserted-by":"crossref","unstructured":"Carr, A.C. & Maggini, S. Vitamin C and Immune Function.\u00a0Nutrients. 9; 1211 (2017).","DOI":"10.3390\/nu9111211"},{"key":"1673_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-018-1996-y","volume":"22","author":"AME Spoelstra-de Man","year":"2018","unstructured":"Spoelstra-de Man, A. M. E., Elbers, P. W. G. & Oudemans-van Straaten, H. M. Making sense of early high-dose intravenous vitamin C in ischemia\/reperfusion injury. Crit. Care 22, 70 (2018).","journal-title":"Crit. Care"},{"key":"1673_CR19","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1056\/NEJMoa1212722","volume":"368","author":"D Heyland","year":"2013","unstructured":"Heyland, D. et al. A randomized trial of glutamine and antioxidants in critically ill patients. N. Engl. J. Med. 368, 1489\u20131497 (2013).","journal-title":"N. Engl. J. Med."},{"key":"1673_CR20","doi-asserted-by":"publisher","first-page":"533","DOI":"10.7326\/0003-4819-140-7-200404060-00010","volume":"140","author":"SJ Padayatty","year":"2004","unstructured":"Padayatty, S. J. et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 140, 533\u2013537 (2004).","journal-title":"Ann. Intern. Med."},{"key":"1673_CR21","doi-asserted-by":"publisher","first-page":"11720","DOI":"10.1073\/pnas.171325998","volume":"98","author":"J Huang","year":"2001","unstructured":"Huang, J. et al. Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke. Proc. Natl. Acad. Sci. USA 98, 11720\u201311724 (2001).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1673_CR22","doi-asserted-by":"publisher","first-page":"7347","DOI":"10.1016\/S0021-9258(17)38398-9","volume":"261","author":"M Levine","year":"1986","unstructured":"Levine, M. Ascorbic acid specifically enhances dopamine beta-monooxygenase activity in resting and stimulated chromaffin cells. J. Biol. Chem. 261, 7347\u20137356 (1986).","journal-title":"J. Biol. Chem."},{"key":"1673_CR23","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1007\/PL00000763","volume":"57","author":"ST Prigge","year":"2000","unstructured":"Prigge, S. T., Mains, R. E., Eipper, B. A. & Amzel, L. M. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell Mol. Life Sci. 57, 1236\u20131259 (2000).","journal-title":"Cell Mol. Life Sci."},{"key":"1673_CR24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.jcrc.2017.09.031","volume":"43","author":"J Teng","year":"2018","unstructured":"Teng, J., Pourmand, A. & Mazer-Amirshahi, M. Vitamin C: The next step in sepsis management? J. Crit. Care 43, 230\u2013234 (2018).","journal-title":"J. Crit. Care"},{"key":"1673_CR25","doi-asserted-by":"publisher","first-page":"e15130","DOI":"10.1371\/journal.pone.0015130","volume":"5","author":"PF Dillon","year":"2010","unstructured":"Dillon, P. F., Root-Bernstein, R., Robinson, N. E., Abraham, W. M. & Berney, C. Receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in vitro and in vivo. PLoS ONE 5, e15130 (2010).","journal-title":"PLoS ONE"},{"key":"1673_CR26","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1055\/s-0032-1315388","volume":"78","author":"J Kallio","year":"2012","unstructured":"Kallio, J., Jaakkola, M., Maki, M., Kilpelainen, P. & Virtanen, V. Vitamin C inhibits Staphylococcus aureus growth and enhances the inhibitory effect of quercetin on growth of Escherichia coli in vitro. Planta Med. 78, 1824\u20131830 (2012).","journal-title":"Planta Med."},{"key":"1673_CR27","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/ajcn\/86.1.145","volume":"86","author":"SJ Padayatty","year":"2007","unstructured":"Padayatty, S. J. et al. Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. Am. J. Clin. Nutr. 86, 145\u2013149 (2007).","journal-title":"Am. J. Clin. Nutr."},{"key":"1673_CR28","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/ACO.0000000000000549","volume":"31","author":"SO Kuhn","year":"2018","unstructured":"Kuhn, S. O., Meissner, K., Mayes, L. M. & Bartels, K. Vitamin C in sepsis. Curr. Opin. Anaesthesiol. 31, 55\u201360 (2018).","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"1673_CR29","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.chest.2016.11.036","volume":"151","author":"PE Marik","year":"2017","unstructured":"Marik, P. E., Khangoora, V., Rivera, R., Hooper, M. H. & Catravas, J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 151, 1229\u20131238 (2017).","journal-title":"Chest"},{"key":"1673_CR30","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1079\/BJN2001406","volume":"86","author":"I Fujita","year":"2001","unstructured":"Fujita, I., Hirano, J., Itoh, N., Nakanishi, T. & Tanaka, K. Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1. Br. J. Nutr. 86, 145\u2013149 (2001).","journal-title":"Br. J. Nutr."},{"key":"1673_CR31","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/S0006-2952(98)00121-X","volume":"56","author":"K Okamoto","year":"1998","unstructured":"Okamoto, K., Tanaka, H., Makino, Y. & Makino, I. Restoration of the glucocorticoid receptor function by the phosphodiester compound of vitamins C and E, EPC-K1 (L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt), via a redox-dependent mechanism. Biochem. Pharmacol. 56, 79\u201386 (1998).","journal-title":"Biochem. Pharmacol."},{"key":"1673_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-32","volume":"12","author":"AA Fowler 3rd","year":"2014","unstructured":"Fowler, A. A. 3rd et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J. Transl. Med. 12, 32 (2014).","journal-title":"J. Transl. Med."},{"key":"1673_CR33","doi-asserted-by":"publisher","first-page":"94","DOI":"10.4103\/2279-042X.179569","volume":"5","author":"MH Zabet","year":"2016","unstructured":"Zabet, M. H., Mohammadi, M., Ramezani, M. & Khalili, H. Effect of high-dose Ascorbic acid on vasopressor\u2019s requirement in septic shock. J. Res. Pharm. Pract. 5, 94\u2013100 (2016).","journal-title":"J. Res. Pharm. Pract."},{"key":"1673_CR34","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1001\/jama.2019.21981","volume":"323","author":"HJ de Grooth","year":"2020","unstructured":"de Grooth, H. J., Elbers, P. W. G. & Vincent, J. L. Vitamin C for sepsis and acute respiratory failure. JAMA 323, 792 (2020).","journal-title":"JAMA"},{"key":"1673_CR35","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1097\/00000658-200212000-00014","volume":"236","author":"AB Nathens","year":"2002","unstructured":"Nathens, A. B. et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann. Surg. 236, 814\u2013822 (2002).","journal-title":"Ann. Surg."},{"key":"1673_CR36","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1097\/01.CCM.0000234033.65657.B6","volume":"34","author":"A Pontes-Arruda","year":"2006","unstructured":"Pontes-Arruda, A., Aragao, A. M. & Albuquerque, J. D. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit. Care Med. 34, 2325\u20132333 (2006).","journal-title":"Crit. Care Med."},{"key":"1673_CR37","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1177\/0885066619864541","volume":"35","author":"F Sadaka","year":"2020","unstructured":"Sadaka, F. et al. Ascorbic acid, thiamine, and steroids in septic shock: propensity matched analysis. J. Intens. Care Med. 35, 1302\u20131306 (2020).","journal-title":"J. Intens. Care Med."},{"key":"1673_CR38","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1001\/jama.2019.22176","volume":"323","author":"T Fujii","year":"2020","unstructured":"Fujii, T. et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the Vitamins Randomized Clinical Trial. JAMA 323, 423\u2013431 (2020).","journal-title":"JAMA"},{"key":"1673_CR39","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1001\/jama.2020.11946","volume":"324","author":"A Moskowitz","year":"2020","unstructured":"Moskowitz, A. et al. Effect of ascorbic acid, corticosteroids, and thiamine on organ injury in septic shock: the ACTS Randomized Clinical Trial. JAMA 324, 642\u2013650 (2020).","journal-title":"JAMA"},{"key":"1673_CR40","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1001\/jama.2020.24505","volume":"325","author":"JE Sevransky","year":"2021","unstructured":"Sevransky, J. E. et al. Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: the VICTAS Randomized Clinical Trial. JAMA 325, 742\u2013750 (2021).","journal-title":"JAMA"},{"key":"1673_CR41","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.chest.2020.02.065","volume":"158","author":"P Chang","year":"2020","unstructured":"Chang, P. et al. Combined treatment with hydrocortisone, vitamin C, and thiamine for sepsis and septic shock: a Randomized Controlled Trial. Chest 158, 174\u2013182 (2020).","journal-title":"Chest"},{"key":"1673_CR42","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.chest.2020.02.049","volume":"158","author":"J Iglesias","year":"2020","unstructured":"Iglesias, J. et al. Outcomes of metabolic resuscitation using ascorbic acid, thiamine, and glucocorticoids in the early treatment of sepsis: the ORANGES Trial. Chest 158, 164\u2013173 (2020).","journal-title":"Chest"},{"key":"1673_CR43","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1093\/jn\/135.7.1673","volume":"135","author":"LK Massey","year":"2005","unstructured":"Massey, L. K., Liebman, M. & Kynast-Gales, S. A. Ascorbate increases human oxaluria and kidney stone risk. J. Nutr. 135, 1673\u20131677 (2005).","journal-title":"J. Nutr."},{"key":"1673_CR44","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/S0022-5347(17)35100-5","volume":"151","author":"TR Wandzilak","year":"1994","unstructured":"Wandzilak, T. R., D\u2019Andre, S. D., Davis, P. A. & Williams, H. E. Effect of high dose vitamin C on urinary oxalate levels. J. Urol. 151, 834\u2013837 (1994).","journal-title":"J. Urol."},{"key":"1673_CR45","doi-asserted-by":"publisher","first-page":"e11414","DOI":"10.1371\/journal.pone.0011414","volume":"5","author":"SJ Padayatty","year":"2010","unstructured":"Padayatty, S. J. et al. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS ONE 5, e11414 (2010).","journal-title":"PLoS ONE"},{"key":"1673_CR46","doi-asserted-by":"crossref","unstructured":"Leite, H. P. & de Lima, L. F. P. in Diet and Nutrition in Critical Care (eds Rajendram, R., Preedy, V. R. & Patel, V.) Ch. 6, 959\u2013972 (Springer, 2015).","DOI":"10.1007\/978-1-4614-7836-2_6"},{"key":"1673_CR47","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.cbi.2006.04.014","volume":"163","author":"F Depeint","year":"2006","unstructured":"Depeint, F., Bruce, W. R., Shangari, N., Mehta, R. & O\u2019Brien, P. J. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem. Biol. Interact. 163, 94\u2013112 (2006).","journal-title":"Chem. Biol. Interact."},{"key":"1673_CR48","doi-asserted-by":"publisher","first-page":"e221","DOI":"10.1542\/peds.2014-2289","volume":"135","author":"S Shah","year":"2015","unstructured":"Shah, S. & Wald, E. Type B lactic acidosis secondary to thiamine deficiency in a child with malignancy. Pediatrics 135, e221\u2013224 (2015).","journal-title":"Pediatrics"},{"key":"1673_CR49","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1476-9255-11-11","volume":"11","author":"JAA de Andrade","year":"2014","unstructured":"de Andrade, J. A. A. et al. The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis. J. Inflamm. 11, 11 (2014).","journal-title":"J. Inflamm."},{"key":"1673_CR50","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1515\/cclm-2017-0054","volume":"55","author":"JTB Collie","year":"2017","unstructured":"Collie, J. T. B. et al. Vitamin B1 in critically ill patients: needs and challenges. Clin. Chem. Lab. Med. 55, 1652\u20131668 (2017).","journal-title":"Clin. Chem. Lab. Med."},{"key":"1673_CR51","doi-asserted-by":"publisher","first-page":"e875","DOI":"10.1097\/CCM.0000000000001745","volume":"44","author":"CS Sassoon","year":"2016","unstructured":"Sassoon, C. S., Zhu, E., Fang, L., Subramanian, V. S. & Said, H. M. Inhibition of intestinal thiamin transport in rat model of sepsis. Crit. Care Med. 44, e875\u2013881 (2016).","journal-title":"Crit. Care Med."},{"key":"1673_CR52","doi-asserted-by":"publisher","first-page":"1214 e1215","DOI":"10.1016\/j.ajem.2017.05.016","volume":"35","author":"RK Dean","year":"2017","unstructured":"Dean, R. K., Subedi, R., Gill, D. & Nat, A. Consideration of alternative causes of lactic acidosis: thiamine deficiency in malignancy. Am. J. Emerg. Med. 35, 1214 e1215\u20131214 e1216 (2017).","journal-title":"Am. J. Emerg. Med."},{"key":"1673_CR53","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.amjms.2018.06.015","volume":"356","author":"P Attaluri","year":"2018","unstructured":"Attaluri, P., Castillo, A., Edriss, H. & Nugent, K. Thiamine deficiency: an important consideration in critically ill patients. Am. J. Med. Sci. 356, 382\u2013390 (2018).","journal-title":"Am. J. Med. Sci."},{"key":"1673_CR54","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1007\/s00134-018-5107-y","volume":"44","author":"K Amrein","year":"2018","unstructured":"Amrein, K., Oudemans-van Straaten, H. M. & Berger, M. M. Vitamin therapy in critically ill patients: focus on thiamine, vitamin C, and vitamin D. Intens. Care Med. 44, 1940\u20131944 (2018).","journal-title":"Intens. Care Med."},{"key":"1673_CR55","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3945\/ajcn.2009.29078","volume":"93","author":"LF Lima","year":"2011","unstructured":"Lima, L. F., Leite, H. P. & Taddei, J. A. Low blood thiamine concentrations in children upon admission to the intensive care unit: risk factors and prognostic significance. Am. J. Clin. Nutr. 93, 57\u201361 (2011).","journal-title":"Am. J. Clin. Nutr."},{"key":"1673_CR56","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jcrc.2017.08.022","volume":"43","author":"MJ Holmberg","year":"2018","unstructured":"Holmberg, M. J. et al. Thiamine in septic shock patients with alcohol use disorders: an observational pilot study. J. Crit. Care 43, 61\u201364 (2018).","journal-title":"J. Crit. Care"},{"key":"1673_CR57","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.nut.2017.11.020","volume":"48","author":"HP Leite","year":"2018","unstructured":"Leite, H. P., de Lima, L. F. P., Taddei, J. & Paes, A. T. Effect of blood thiamine concentrations on mortality: influence of nutritional status. Nutrition 48, 105\u2013110 (2018).","journal-title":"Nutrition"},{"key":"1673_CR58","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.jcrc.2010.03.003","volume":"25","author":"MW Donnino","year":"2010","unstructured":"Donnino, M. W. et al. Thiamine deficiency in critically ill patients with sepsis. J. Crit. Care 25, 576\u2013581 (2010).","journal-title":"J. Crit. Care"},{"key":"1673_CR59","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.resuscitation.2016.04.024","volume":"105","author":"K Ikeda","year":"2016","unstructured":"Ikeda, K. et al. Thiamine as a neuroprotective agent after cardiac arrest. Resuscitation 105, 138\u2013144 (2016).","journal-title":"Resuscitation"},{"key":"1673_CR60","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1097\/00003246-198910000-00014","volume":"17","author":"GA Lindenbaum","year":"1989","unstructured":"Lindenbaum, G. A., Larrieu, A. J., Carroll, S. F. & Kapusnick, R. A. Effect of cocarboxylase in dogs subjected to experimental septic shock. Crit. Care Med. 17, 1036\u20131040 (1989).","journal-title":"Crit. Care Med."},{"key":"1673_CR61","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1513\/AnnalsATS.201608-656BC","volume":"14","author":"A Moskowitz","year":"2017","unstructured":"Moskowitz, A. et al. Thiamine as a renal protective agent in septic shock. a secondary analysis of a Randomized, Double-Blind, Placebo-Controlled Trial. Ann. Am. Thorac. Soc. 14, 737\u2013741 (2017).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"1673_CR62","doi-asserted-by":"publisher","first-page":"e452","DOI":"10.1097\/PCC.0000000000002074","volume":"20","author":"SL Weiss","year":"2019","unstructured":"Weiss, S. L. et al. Matched retrospective cohort study of thiamine to treat persistent hyperlactatemia in pediatric septic shock. Pediatr. Crit. Care Med. 20, e452\u2013e456 (2019).","journal-title":"Pediatr. Crit. Care Med."},{"key":"1673_CR63","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0735-6757(92)90054-2","volume":"10","author":"KD Wrenn","year":"1992","unstructured":"Wrenn, K. D. & Slovis, C. M. Is intravenous thiamine safe? Am. J. Emerg. Med. 10, 165 (1992).","journal-title":"Am. J. Emerg. Med."},{"key":"1673_CR64","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1515\/jpem-2017-0554","volume":"31","author":"H Ozdemir","year":"2018","unstructured":"Ozdemir, H. et al. Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency. J. Pediatr. Endocrinol. Metab. 31, 693\u2013695 (2018).","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"1673_CR65","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.nut.2015.08.007","volume":"32","author":"UA Qureshi","year":"2016","unstructured":"Qureshi, U. A. et al. Thiamine responsive acute life threatening metabolic acidosis in exclusively breast-fed infants. Nutrition 32, 213\u2013216 (2016).","journal-title":"Nutrition"},{"key":"1673_CR66","doi-asserted-by":"publisher","first-page":"e1670","DOI":"10.1542\/peds.2012-2988","volume":"131","author":"B Perez-Duenas","year":"2013","unstructured":"Perez-Duenas, B. et al. Reversible lactic acidosis in a newborn with thiamine transporter-2 deficiency. Pediatrics 131, e1670\u20131675 (2013).","journal-title":"Pediatrics"},{"key":"1673_CR67","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1056\/NEJMra070553","volume":"357","author":"MF Holick","year":"2007","unstructured":"Holick, M. F. Vitamin D deficiency. N. Engl. J. Med. 357, 266\u2013281 (2007).","journal-title":"N. Engl. J. Med."},{"key":"1673_CR68","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.rdc.2012.03.012","volume":"38","author":"M Hewison","year":"2012","unstructured":"Hewison, M. Vitamin D and the immune system: new perspectives on an old theme. Rheum. Dis. Clin. N. Am. 38, 125\u2013139 (2012).","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"1673_CR69","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1126\/science.1123933","volume":"311","author":"PT Liu","year":"2006","unstructured":"Liu, P. T. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770\u20131773 (2006).","journal-title":"Science"},{"key":"1673_CR70","doi-asserted-by":"publisher","first-page":"e85765","DOI":"10.1371\/journal.pone.0085765","volume":"9","author":"Z Hu","year":"2014","unstructured":"Hu, Z. et al. Antimicrobial cathelicidin peptide LL-37 inhibits the LPS\/ATP-induced pyroptosis of macrophages by dual mechanism. PLoS ONE 9, e85765 (2014).","journal-title":"PLoS ONE"},{"key":"1673_CR71","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/intimm\/dxq471","volume":"23","author":"K Suzuki","year":"2011","unstructured":"Suzuki, K. et al. Human anti-microbial cathelicidin peptide LL-37 suppresses the LPS-induced apoptosis of endothelial cells. Int. Immunol. 23, 185\u2013193 (2011).","journal-title":"Int. Immunol."},{"key":"1673_CR72","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1471-230X-12-57","volume":"12","author":"H Zhao","year":"2012","unstructured":"Zhao, H. et al. Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC Gastroenterol. 12, 57 (2012).","journal-title":"BMC Gastroenterol."},{"key":"1673_CR73","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1210\/me.2013-1146","volume":"27","author":"J Kong","year":"2013","unstructured":"Kong, J. et al. VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system. Mol. Endocrinol. 27, 2116\u20132125 (2013).","journal-title":"Mol. Endocrinol."},{"key":"1673_CR74","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1875-y","volume":"21","author":"JD McNally","year":"2017","unstructured":"McNally, J. D. et al. Vitamin D deficiency in critically ill children: a systematic review and meta-analysis. Crit. Care 21, 287 (2017).","journal-title":"Crit. Care"},{"key":"1673_CR75","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1097\/MCO.0b013e328358fc2b","volume":"15","author":"SA Quraishi","year":"2012","unstructured":"Quraishi, S. A. & Camargo, C. A. Jr. Vitamin D in acute stress and critical illness. Curr. Opin. Clin. Nutr. Metab. Care 15, 625\u2013634 (2012).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"1673_CR76","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jcrc.2017.09.179","volume":"43","author":"T Czarnik","year":"2018","unstructured":"Czarnik, T. et al. Vitamin D kinetics in the acute phase of critical illness: A prospective observational study. J. Crit. Care 43, 294\u2013299 (2018).","journal-title":"J. Crit. Care"},{"key":"1673_CR77","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4529-7","volume":"19","author":"CH Li","year":"2019","unstructured":"Li, C. H. et al. Mechanistic study of the cause of decreased blood 1,25-dihydroxyvitamin D in sepsis. BMC Infect. Dis. 19, 1020 (2019).","journal-title":"BMC Infect. Dis."},{"key":"1673_CR78","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1055\/s-0037-1615681","volume":"85","author":"H Asakura","year":"2001","unstructured":"Asakura, H. et al. Beneficial effect of the active form of vitamin D3 against LPS-induced DIC but not against tissue-factor-induced DIC in rat models. Thromb. Haemost. 85, 287\u2013290 (2001).","journal-title":"Thromb. Haemost."},{"key":"1673_CR79","doi-asserted-by":"publisher","first-page":"190","DOI":"10.7150\/ijms.4.190","volume":"4","author":"S Moller","year":"2007","unstructured":"Moller, S., Laigaard, F., Olgaard, K. & Hemmingsen, C. Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis. Int. J. Med. Sci. 4, 190\u2013195 (2007).","journal-title":"Int. J. Med. Sci."},{"key":"1673_CR80","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/BF01986584","volume":"33","author":"H Horiuchi","year":"1991","unstructured":"Horiuchi, H., Nagata, I. & Komoriya, K. Protective effect of vitamin D3 analogues on endotoxin shock in mice. Agents Actions 33, 343\u2013348 (1991).","journal-title":"Agents Actions"},{"key":"1673_CR81","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/j.1365-2249.2005.02961.x","volume":"143","author":"O Equils","year":"2006","unstructured":"Equils, O. et al. 1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clin. Exp. Immunol. 143, 58\u201364 (2006).","journal-title":"Clin. Exp. Immunol."},{"key":"1673_CR82","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s13312-016-0876-2","volume":"53","author":"SK Shah","year":"2016","unstructured":"Shah, S. K., Kabra, S. K., Gupta, N., Pai, G. & Lodha, R. Vitamin D deficiency and parathyroid response in critically-ill children: association with illness severity and clinical outcomes. Indian Pediatr. 53, 479\u2013484 (2016).","journal-title":"Indian Pediatr."},{"key":"1673_CR83","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1007\/s00134-012-2718-6","volume":"38","author":"C Rippel","year":"2012","unstructured":"Rippel, C., South, M., Butt, W. W. & Shekerdemian, L. S. Vitamin D status in critically ill children. Intens. Care Med. 38, 2055\u20132062 (2012).","journal-title":"Intens. Care Med."},{"key":"1673_CR84","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1542\/peds.2011-3328","volume":"130","author":"K Madden","year":"2012","unstructured":"Madden, K. et al. Vitamin D deficiency in critically ill children. Pediatrics 130, 421\u2013428 (2012).","journal-title":"Pediatrics"},{"key":"1673_CR85","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1016\/j.clnu.2019.08.010","volume":"39","author":"D Xiao","year":"2020","unstructured":"Xiao, D. et al. Association between vitamin D status and sepsis in children: a meta-analysis of observational studies. Clin. Nutr. 39, 1735\u20131741 (2020).","journal-title":"Clin. Nutr."},{"key":"1673_CR86","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0660-4","volume":"18","author":"K de Haan","year":"2014","unstructured":"de Haan, K., Groeneveld, A. B., de Geus, H. R., Egal, M. & Struijs, A. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. Crit. Care 18, 660 (2014).","journal-title":"Crit. Care"},{"key":"1673_CR87","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0684-9","volume":"18","author":"YP Zhang","year":"2014","unstructured":"Zhang, Y. P., Wan, Y. D., Sun, T. W., Kan, Q. C. & Wang, L. X. Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies. Crit. Care 18, 684 (2014).","journal-title":"Crit. Care"},{"key":"1673_CR88","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1179\/2046905515Y.0000000042","volume":"36","author":"S Ponnarmeni","year":"2016","unstructured":"Ponnarmeni, S. et al. Vitamin D deficiency in critically ill children with sepsis. Paediatr. Int. Child Health 36, 15\u201321 (2016).","journal-title":"Paediatr. Int. Child Health"},{"key":"1673_CR89","doi-asserted-by":"crossref","unstructured":"He, M., Cao, T., Wang, J., Wang, C., Wang, Z.., Abdelrahim, M.E.A. Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children: A meta-analysis. Int. J. Clin. Pract. 75, e13908 (2021).","DOI":"10.1111\/ijcp.13908"},{"key":"1673_CR90","doi-asserted-by":"publisher","first-page":"e23827","DOI":"10.1097\/MD.0000000000023827","volume":"100","author":"W Yu","year":"2021","unstructured":"Yu, W., Ying, Q., Zhu, W., Huang, L. & Hou, Q. Vitamin D status was associated with sepsis in critically ill children: A PRISMA compliant systematic review and meta-analysis. Medicine 100, e23827 (2021).","journal-title":"Medicine"},{"key":"1673_CR91","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jinf.2011.07.002","volume":"63","author":"RR Watkins","year":"2011","unstructured":"Watkins, R. R., Yamshchikov, A. V., Lemonovich, T. L. & Salata, R. A. The role of vitamin D deficiency in sepsis and potential therapeutic implications. J. Infect. 63, 321\u2013326 (2011).","journal-title":"J. Infect."},{"key":"1673_CR92","first-page":"36","volume":"10","author":"E Mathias","year":"2017","unstructured":"Mathias, E., Tangpricha, V., Sarnaik, A., Farooqi, A. & Sethuraman, U. Association of vitamin D with cathelicidin and vitamin D binding protein in pediatric sepsis. J. Clin. Transl. Endocrinol. 10, 36\u201338 (2017).","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"1673_CR93","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1164\/rccm.201405-0988OC","volume":"190","author":"DE Leaf","year":"2014","unstructured":"Leaf, D. E., Raed, A., Donnino, M. W., Ginde, A. A. & Waikar, S. S. Randomized controlled trial of calcitriol in severe sepsis. Am. J. Respir. Crit. Care Med. 190, 533\u2013541 (2014).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"1673_CR94","first-page":"59","volume":"4","author":"JE Han","year":"2016","unstructured":"Han, J. E. et al. High dose vitamin D administration in ventilated intensive care unit patients: a Pilot Double Blind Randomized Controlled Trial. J. Clin. Transl. Endocrinol. 4, 59\u201365 (2016).","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"1673_CR95","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1001\/jama.2014.13204","volume":"312","author":"K Amrein","year":"2014","unstructured":"Amrein, K. et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 312, 1520\u20131530 (2014).","journal-title":"JAMA"},{"key":"1673_CR96","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s00134-016-4591-1","volume":"43","author":"H Weng","year":"2017","unstructured":"Weng, H., Li, J. G., Mao, Z. & Zeng, X. T. Randomised trials of vitamin D3 for critically ill patients in adults: systematic review and meta-analysis with trial sequential analysis. Intens. Care Med. 43, 277\u2013278 (2017).","journal-title":"Intens. Care Med."},{"key":"1673_CR97","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71271-9","volume":"10","author":"SH Lan","year":"2020","unstructured":"Lan, S. H. et al. Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials. Sci. Rep. 10, 14261 (2020).","journal-title":"Sci. Rep."},{"key":"1673_CR98","doi-asserted-by":"crossref","first-page":"300060520926890","DOI":"10.1177\/0300060520926890","volume":"48","author":"Y Wang","year":"2020","unstructured":"Wang, Y., Yang, Z., Gao, L., Cao, Z. & Wang, Q. Effects of a single dose of vitamin D in septic children: a randomized, double-blinded, controlled trial. J. Intern. Med. Res. 48, 300060520926890 (2020).","journal-title":"J. Intern. Med. Res."},{"key":"1673_CR99","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/MAJ.0000000000000360","volume":"349","author":"MD Kearns","year":"2015","unstructured":"Kearns, M. D., Alvarez, J. A., Seidel, N. & Tangpricha, V. Impact of vitamin D on infectious disease. Am. J. Med Sci. 349, 245\u2013262 (2015).","journal-title":"Am. J. Med Sci."},{"key":"1673_CR100","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1210\/jc.2013-3655","volume":"99","author":"MG Vogiatzi","year":"2014","unstructured":"Vogiatzi, M. G., Jacobson-Dickman, E. & DeBoer, M. D. Drugs & Therapeutics Committee of The Pediatric Endocrine, S. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J. Clin. Endocrinol. Metab. 99, 1132\u20131141 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1673_CR101","doi-asserted-by":"publisher","DOI":"10.1186\/s40814-017-0214-z","volume":"3","author":"D McNally","year":"2017","unstructured":"McNally, D. et al. Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study). Pilot Feasibility Stud. 3, 70 (2017).","journal-title":"Pilot Feasibility Stud."},{"key":"1673_CR102","doi-asserted-by":"publisher","first-page":"1816S","DOI":"10.3945\/jn.115.229708","volume":"146","author":"SA Tanumihardjo","year":"2016","unstructured":"Tanumihardjo, S. A. et al. Biomarkers of Nutrition for Development (BOND)\u2014vitamin A review. J. Nutr. 146, 1816S\u20131848S (2016).","journal-title":"J. Nutr."},{"key":"1673_CR103","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1016\/S0168-8227(01)00331-X","volume":"54","author":"CD Berdanier","year":"2001","unstructured":"Berdanier, C. D., Everts, H. B., Hermoyian, C. & Mathews, C. E. Role of vitamin A in mitochondrial gene expression. Diabetes Res. Clin. Pract. 54, S11\u2013S27 (2001).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"1673_CR104","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1093\/ajcn\/60.3.388","volume":"60","author":"CB Stephensen","year":"1994","unstructured":"Stephensen, C. B. et al. Vitamin A is excreted in the urine during acute infection. Am. J. Clin. Nutr. 60, 388\u2013392 (1994).","journal-title":"Am. J. Clin. Nutr."},{"key":"1673_CR105","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s001340050813","volume":"25","author":"P Metnitz","year":"1999","unstructured":"Metnitz, P. et al. Antioxidant status in patients with acute respiratory distress syndrome. Intens. Care Med. 25, 180\u2013185 (1999).","journal-title":"Intens. Care Med."},{"key":"1673_CR106","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/j.1472-8206.2008.00573.x","volume":"22","author":"JM Doise","year":"2008","unstructured":"Doise, J. M. et al. Plasma antioxidant status in septic critically ill patients: a decrease over time. Fundam. Clin. Pharmacol. 22, 203\u2013209 (2008).","journal-title":"Fundam. Clin. Pharmacol."},{"key":"1673_CR107","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1097\/00003246-199504000-00011","volume":"23","author":"HF Goode","year":"1995","unstructured":"Goode, H. F., Cowley, H. C., Walker, B. E., Howdle, P. D. & Webster, N. R. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit. Care Med. 23, 646\u2013651 (1995).","journal-title":"Crit. Care Med."},{"key":"1673_CR108","doi-asserted-by":"publisher","first-page":"e455","DOI":"10.1097\/PCC.0000000000001626","volume":"19","author":"FV Valla","year":"2018","unstructured":"Valla, F. V. et al. Multiple micronutrient plasma level changes are related to oxidative stress intensity in critically ill children. Pediatr. Crit. Care Med. 19, e455\u2013e463 (2018).","journal-title":"Pediatr. Crit. Care Med."},{"key":"1673_CR109","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76251-7","volume":"10","author":"H Ahn","year":"2020","unstructured":"Ahn, H. & Lee, G. S. Riboflavin, vitamin B2, attenuates NLRP3, NLRC4, AIM2, and non-canonical inflammasomes by the inhibition of caspase-1 activity. Sci. Rep. 10, 19091 (2020).","journal-title":"Sci. Rep."},{"key":"1673_CR110","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1128\/IAI.72.3.1820-1823.2004","volume":"72","author":"T Toyosawa","year":"2004","unstructured":"Toyosawa, T., Suzuki, M., Kodama, K. & Araki, S. Highly purified vitamin B2 presents a promising therapeutic strategy for sepsis and septic shock. Infect. Immun. 72, 1820\u20131823 (2004).","journal-title":"Infect. Immun."},{"key":"1673_CR111","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.ejphar.2004.04.004","volume":"492","author":"T Toyosawa","year":"2004","unstructured":"Toyosawa, T., Suzuki, M., Kodama, K. & Araki, S. Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice. Eur. J. Pharmacol. 492, 273\u2013280 (2004).","journal-title":"Eur. J. Pharmacol."},{"key":"1673_CR112","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1016\/j.fct.2010.04.033","volume":"48","author":"CK Shih","year":"2010","unstructured":"Shih, C. K. et al. Riboflavin protects mice against liposaccharide-induced shock through expression of heat shock protein 25. Food Chem. Toxicol. 48, 1913\u20131918 (2010).","journal-title":"Food Chem. Toxicol."},{"key":"1673_CR113","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1177\/1535370214535896","volume":"239","author":"T Barichello","year":"2014","unstructured":"Barichello, T. et al. Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis. Exp. Biol. Med. 239, 1360\u20131365 (2014).","journal-title":"Exp. Biol. Med."},{"key":"1673_CR114","doi-asserted-by":"crossref","unstructured":"Giustina, A. D. et al. Vitamin B6 reduces oxidative stress in lungs and liver in experimental sepsis. An. Acad. Bras. Ci\u00eanc. 91, e20190434 (2019).","DOI":"10.1590\/0001-3765201920190434"},{"key":"1673_CR115","doi-asserted-by":"publisher","first-page":"5255","DOI":"10.1007\/s12035-017-0706-0","volume":"55","author":"LG Danielski","year":"2018","unstructured":"Danielski, L. G. et al. Vitamin B6 reduces neurochemical and long-term cognitive alterations after polymicrobial sepsis: involvement of the kynurenine pathway modulation. Mol. Neurobiol. 55, 5255\u20135268 (2018).","journal-title":"Mol. Neurobiol."},{"key":"1673_CR116","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1177\/0310057X1604400410","volume":"44","author":"M Romain","year":"2016","unstructured":"Romain, M., Sviri, S., Linton, D., Stav, I. & van Heerden, P. V. The role of vitamin B12 in the critically ill\u2014a review. Anaesth. Intens. Care 44, 447\u2013452 (2016).","journal-title":"Anaesth. Intens. Care"},{"key":"1673_CR117","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.freeradbiomed.2009.04.023","volume":"47","author":"CS Birch","year":"2009","unstructured":"Birch, C. S., Brasch, N. E., McCaddon, A. & Williams, J. H. H. A novel role for vitamin B12: cobalamins are intracellular antioxidants in vitro. Free Radic. Biol. Med. 47, 184\u2013188 (2009).","journal-title":"Free Radic. Biol. Med."},{"key":"1673_CR118","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1097\/MCO.0b013e32833dfaec","volume":"13","author":"W Manzanares","year":"2010","unstructured":"Manzanares, W. & Hardy, G. Vitamin B12: the forgotten micronutrient for critical care. Curr. Opin. Clin. Nutr. Metab. Care 13, 662\u2013668 (2010).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"1673_CR119","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1016\/j.freeradbiomed.2009.03.017","volume":"46","author":"JB Weinberg","year":"2009","unstructured":"Weinberg, J. B. et al. Inhibition of nitric oxide synthase by cobalamins and cobinamides. Free Radic. Biol. Med. 46, 1626\u20131632 (2009).","journal-title":"Free Radic. Biol. Med."},{"key":"1673_CR120","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.mehy.2006.01.036","volume":"67","author":"C Wheatley","year":"2006","unstructured":"Wheatley, C. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock. Med. Hypotheses 67, 124\u2013142 (2006).","journal-title":"Med. Hypotheses"},{"key":"1673_CR121","unstructured":"Chudow, M. & Adams, B. ABC\u2019s of vitamin supplementation in critical illness. J. Pharm. Pract. 897190020958234 (2020)."},{"key":"1673_CR122","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2014.03.035","volume":"72","author":"Q Jiang","year":"2014","unstructured":"Jiang, Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic. Biol. Med. 72, 76\u201390 (2014).","journal-title":"Free Radic. Biol. Med."},{"key":"1673_CR123","doi-asserted-by":"crossref","unstructured":"Minter, B. E., Lowes, D. A., Webster, N. R. & Galley, H. F. Differential effects of MitoVitE, alpha-tocopherol and trolox on oxidative stress, mitochondrial function and inflammatory signalling pathways in endothelial cells cultured under conditions mimicking sepsis. Antioxidants 9, 195 (2020).","DOI":"10.3390\/antiox9030195"},{"key":"1673_CR124","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1054\/plef.2000.0141","volume":"62","author":"S Basu","year":"2000","unstructured":"Basu, S. & Eriksson, M. Vitamin E in relation to lipid peroxidation in experimental septic shock. Prostaglandins Leukot. Essent. Fatty Acids 62, 195\u2013199 (2000).","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"1673_CR125","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1001\/archsurg.1997.01430360083015","volume":"132","author":"EM Bulger","year":"1997","unstructured":"Bulger, E. M. et al. Enteral vitamin E supplementation inhibits the cytokine response to endotoxin. Arch. Surg. 132, 1337\u20131341 (1997).","journal-title":"Arch. Surg."},{"key":"1673_CR126","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/BF00257683","volume":"13","author":"W Seeger","year":"1987","unstructured":"Seeger, W., Ziegler, A. & Wolf, H. Serum alpha-tocopherol levels after high-dose enteral vitamin E administration in patients with acute respiratory failure. Intens. Care Med. 13, 395\u2013400 (1987).","journal-title":"Intens. Care Med."},{"key":"1673_CR127","doi-asserted-by":"crossref","unstructured":"Carcillo, J. A. et al. A Multicenter network assessment of three inflammation phenotypes in pediatric sepsis-induced multiple organ failure. Pediatr. Crit. Care Med.\u00a020, 1137\u20131146 (2019).","DOI":"10.1097\/PCC.0000000000002105"},{"key":"1673_CR128","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1001\/jama.2019.5791","volume":"321","author":"CW Seymour","year":"2019","unstructured":"Seymour, C. W. et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA 321, 2003\u20132017 (2019).","journal-title":"JAMA"},{"key":"1673_CR129","doi-asserted-by":"publisher","first-page":"e1000","DOI":"10.1097\/CCM.0000000000001833","volume":"44","author":"HR Wong","year":"2016","unstructured":"Wong, H. R. et al. Combining prognostic and predictive enrichment strategies to identify children with septic shock responsive to corticosteroids. Crit. Care Med. 44, e1000\u20131003 (2016).","journal-title":"Crit. Care Med."},{"key":"1673_CR130","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1001\/jama.2012.4174","volume":"307","author":"WJ Meurer","year":"2012","unstructured":"Meurer, W. J., Lewis, R. J. & Berry, D. A. Adaptive clinical trials: a partial remedy for the therapeutic misconception? JAMA 307, 2377\u20132378 (2012).","journal-title":"JAMA"},{"key":"1673_CR131","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1836-5","volume":"21","author":"CW Seymour","year":"2017","unstructured":"Seymour, C. W. et al. Precision medicine for all? Challenges and opportunities for a precision medicine approach to critical illness. Crit. Care 21, 257 (2017).","journal-title":"Crit. Care"},{"key":"1673_CR132","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1001\/archsurg.135.3.326","volume":"135","author":"H Tanaka","year":"2000","unstructured":"Tanaka, H. et al. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch. Surg. 135, 326\u201331 (2000).","journal-title":"Arch. Surg."},{"key":"1673_CR133","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.21037\/jtd.2019.03.03","volume":"11","author":"JH Ahn","year":"2019","unstructured":"Ahn, J. H. et al. Vitamin C alone does not improve treatment outcomes in mechanically ventilated patients with severe sepsis or septic shock: a retrospective cohort study. J. Thorac. Dis. 11, 1562\u201370 (2019).","journal-title":"J. Thorac. Dis."},{"key":"1673_CR134","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2693-1","volume":"23","author":"M Nakajima","year":"2019","unstructured":"Nakajima, M. et al. Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study. Crit. Care 23, 407 (2019).","journal-title":"Crit. Care"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01673-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01673-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01673-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T09:00:49Z","timestamp":1744189249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-021-01673-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,31]]},"references-count":134,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["1673"],"URL":"https:\/\/doi.org\/10.1038\/s41390-021-01673-6","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,31]]},"assertion":[{"value":"2 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}