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      25-hydroxyvitamin D and parathyroid hormone in new onset sepsis: A prospective study in critically ill patients

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          Abstract

          Hypovitaminosis D is highly prevalent in critically ill patients, and it has been suggested to be a risk factor for infections, sepsis and higher mortality. We sought to investigate whether serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in critically ill patients with new onset sepsis are associated with severity and outcome. We prospectively included 50 consecutive critically ill adult cases with new onset sepsis and 50 healthy controls matched for age and sex. PTH and 25(OH)D were determined in serum via electrochemiluminescence immunoassays at inclusion in the study in all cases and controls, and one week after sepsis onset in cases. Patients had reduced 25(OH)D compared to controls at sepsis onset (7.9 ± 3 vs 24.6 ± 6.7 ng/mL, p < 0.001), whilst PTH was similar (median (range): 34.5 (5.7–218.5) vs 44.2 (14.2–98.1) pg/mL, p = 0.35). In patients, 25(OH)D upon enrollment and one week after did not differ significantly (7.9 ± 3 vs 7 ± 4.3 ng/mL, p = 0.19). All patients presented with hypovitaminosis D (25(OH)D < 20 ng/mL), while 40 patients (80 %) had vitamin D deficiency (25(OH)D < 12 ng/mL) at sepsis onset, including all ten (20 %) nonsurvivors, who died within 28 days from sepsis onset. Patients with sepsis (N = 28) and septic shock (N = 22) as well as survivors (N = 40) and nonsurvivors (N = 10) had similar 25(OH)D at enrollment (p > 0.05). 25(OH)D was positively correlated with ionized calcium (r = 0.46, p < 0.001) and negatively with PTH (p < 0.05), while inflammatory biomarkers or the severity scores exhibited no correlation with 25(OH)D. Patients with septic shock and nonsurvivors had lower PTH than patients with sepsis and survivors respectively (42.2 ± 42.9 vs 73.4 ± 61.9 pg/mL, p = 0.04, and 18.3 ± 10.7 vs 69.9 ± 58.8 pg/mL, p = 0.001, respectively). C-reactive protein was negatively associated with PTH (r = −0.44, p = 0.001). In conclusion, vitamin D deficiency was present in 80 % of critically ill patients at sepsis onset, while nonsurvivors exhibited lower PTH than survivors. Additional, larger and multicenter studies are warranted to elucidate the contribution of vitamin D and PTH to the pathogenesis of sepsis and its outcomes.

          Highlights

          • Vitamin D deficiency was detected in 80 % of our study cohort at sepsis onset.

          • Circulating 25(OH)D was not linked to sepsis severity and outcome.

          • Parathyroid hormone was significantly decreased in nonsurvivors compared to survivors.

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          Most cited references51

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study

            Abstract Aim To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID‐19) infection and hospitalization. Methods The study population included the 14,000 members of Leumit Health Services who were tested for COVID‐19 infection from February 1st to April 30th 2020, and who had at least one previous blood test for plasma 25(OH)D level. "Suboptimal" or "low" plasma 25(OH)D level was defined as plasma 25‐hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL. Results Of 7,807 individuals, 782 (10.1%) were COVID‐19‐positive, and 7,025 (89.9%) COVID‐19‐negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19 [19.00 ng/mL (95% confidence interval [CI] 18.41‐19.59) vs. 20.55 (95% CI 20.32‐20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID‐19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24‐2.01, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [crude OR of 2.09 (95% CI 1.01‐ 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID‐19 infection [1.45 (95% CI 1.08‐1.95, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [1.95 (95% CI 0.98‐4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low‐medium socioeconomic status were also positively associated with the risk of COVID‐19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID‐19. Conclusion Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization.
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              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.

              Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. clinicaltrials.gov Identifier: NCT01130181.
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                Author and article information

                Contributors
                Journal
                Metabol Open
                Metabol Open
                Metabolism Open
                Elsevier
                2589-9368
                15 June 2024
                September 2024
                15 June 2024
                : 23
                : 100296
                Affiliations
                [a ]Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari, 12462, Athens, Greece
                [b ]Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias St., Goudi, 11527, Athens, Greece
                [c ]Department of Endocrinology, Evangelismos General Hospital, 45-47 Ipsilantou St., 10676, Athens, Greece
                [d ]Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari, 12462, Athens, Greece
                [e ]Department of Internal Medicine, Hippokration General Hospital, 114 Vasilissis Sofias St., 11527, Athens, Greece
                [f ]Department of Internal Medicine, Sismanogleio General Hospital, 1 Sismanogleiou St., 15126, Athens, Greece
                [g ]First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100, Alexandroupolis, Greece
                Author notes
                [* ]Corresponding author. Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari, 12462, Athens, Greece. eikaras1@ 123456gmail.com
                Article
                S2589-9368(24)00028-8 100296
                10.1016/j.metop.2024.100296
                11228765
                2fb9cdd9-4487-42fd-b6d2-86841721118e
                © 2024 The Authors

                This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 30 May 2024
                : 15 June 2024
                : 15 June 2024
                Categories
                Original Research Paper

                critical illness,hypovitaminosis d,parathyroid hormone,sepsis,vitamin d,1,25-dihydroxyvitamin d

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