The trace element selenium is of high importance for many of the body's regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly ...increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.
Patients in the intervention group had 10% higher lactate levels, were more often in shock and mechanically ventilated already at baseline. ...compared to placebo, patients receiving vitamin C ...appeared to be sicker, overall contributing to the higher risk of organ dysfunction. ...numerous RCTs assessing the effects of IV vitamin C have been performed in critically ill patients followed by several systematic reviews and meta-analyses (SRMA) 7. ...in most of the trials, patients were included largely based on undifferentiated phenotypes, likely having a different mortality risk and also different treatment response 12, 13. ...imbalances in sepsis phenotypes may have contributed to the heterogeneity in response to vitamin C in the different trials. ...no surrogate markers of vitamin C were measured and the average vitamin C level (measured in a sub-cohort) was in the normal range, whereas patients with vitamin C deficiency are known to most likely to benefit from a supplementation.
Oxidative stress contributes to organ dysfunction after cardiac surgery and still represents a major problem. Antioxidants, such as vitamins C and E might be organ protective.
The primary objective ...of this prospective observational study was the description to evaluate the perioperative vitamin C and E levels in 56 patients undergoing cardiac surgery with the use of cardiopulmonary bypass. The association of vitamin C with inflammatory reaction, oxidative stress, organ dysfunctions, and clinical outcomes were evaluated in an explorative approach.
Vitamin C levels decreased significantly from 6.5 (3.5-11.5) mg/L before surgery to 2.8 (2.0-3.9) mg/L 48 h after surgery (
< 0.0001). Fifty-six percent of patients had a suboptimal vitamin C status even before surgery. In protein-denaturized probes, significantly higher vitamin C concentrations were detected (
= 0.0008). Vitamin E levels decreased significantly from preoperative level 11.6 (9.5-13.2) mg/L to 7.1 (5.5-7.4) mg/L, (
= 0.0002) at the end of cardiopulmonary bypass, remained low during the first day on ICU and recovered to 8.2 (7.1-9.3) mg/L 48 h after surgery. No patient was vitamin E deficient before surgery. Analysis showed no statistically significant association of vitamin C with inflammation, oxidative stress or organ dysfunction levels in patients with previously suboptimal vitamin C status or patients with a perioperative decrease of ≥50% vitamin C after surgery. Patients with higher vitamin C levels had a shorter ICU stay than those who were vitamin C depleted, which was not statistically significant (72 versus 135 h,
= 0.1990).
Vitamin C and E levels significantly declined intraoperatively and remained significantly reduced low for 2 days after cardiac surgery. The influence of reduced serum levels on the inflammatory reaction and clinical outcome of the patients remain unclear in this small observational study and need to be investigated further. Given vitamin C´s pleiotropic role in the human defense mechanisms, further trials are encouraged to evaluate the clinical significance of Vitamin C in cardiac surgery patients.
Selenoprotein P (SELENOP) is an established biomarker of selenium (Se) status. Serum SELENOP becomes saturated with increasing Se intake, reaching maximal concentrations of 5-7 mg SELENOP/L at ...intakes of ca. 100-150 µg Se/d. A biomarker for higher Se intake is missing. We hypothesized that SELENOP may also reflect Se status in clinical applications of therapeutic dosages of selenite. To this end, blood samples from two supplementation studies employing intravenous application of selenite at dosages >1 mg/d were analyzed. Total Se was quantified by spectroscopy, and SELENOP by a validated ELISA. The high dosage selenite infusions increased SELENOP in parallel to elevated Se concentrations relatively fast to final values partly exceeding 10 mg SELENOP/L. Age or sex were not related to the SELENOP increase. Western blot analyses of SELENOP verified the results obtained by ELISA, and indicated an unchanged pattern of immunoreactive protein isoforms. We conclude that the saturation of SELENOP concentrations observed in prior studies with moderate Se dosages (<400 µg/d) may reflect an intermediate plateau of expression, rather than an absolute upper limit. Circulating SELENOP seems to be a suitable biomarker for therapeutic applications of selenite exceeding the recommended upper intake levels. Whether SELENOP is also capable of reflecting other supplemental selenocompounds in high dosage therapeutic applications remains to be investigated.
Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of ...reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients.
A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed.
1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval CI 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio RR 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference WMD - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care.
Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238).
We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing ...open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p < 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (p < 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (p < 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The cardiac vascular and perivascular niche are of major importance in homeostasis and during disease, but we lack a complete understanding of its cellular heterogeneity and alteration in response to ...injury as a major driver of heart failure. Using combined genetic fate tracing with confocal imaging and single-cell RNA sequencing of this niche in homeostasis and during heart failure, we unravel cell type specific transcriptomic changes in fibroblast, endothelial, pericyte and vascular smooth muscle cell subtypes. We characterize a specific fibroblast subpopulation that exists during homeostasis, acquires Thbs4 expression and expands after injury driving cardiac fibrosis, and identify the transcription factor TEAD1 as a regulator of fibroblast activation. Endothelial cells display a proliferative response after injury, which is not sustained in later remodeling, together with transcriptional changes related to hypoxia, angiogenesis, and migration. Collectively, our data provides an extensive resource of transcriptomic changes in the vascular niche in hypertrophic cardiac remodeling.
Abstract
Background
The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate ...the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.
Methods
Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.
Results
Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97,
p
= 0.03;
I
2
= 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89,
n
= 1250,
p
= 0.006;
I
2
= 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73,
n
= 572,
p
< 0.0001;
I
2
= 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences,
p
= 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.
Conclusions
Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.
Trial registration
: PROSPERO international prospective database of systematic reviews (CRD42021256939—05 July 2021).
Biomarkers in critical care nutrition Stoppe, Christian; Wendt, Sebastian; Mehta, Nilesh M ...
Critical care,
08/2020, Volume:
24, Issue:
1
Journal Article
Peer reviewed
Open access
The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of ...lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.
Initial evidence indicates that preoperatively initiated administration of omega-3 fatty acids (FAs) attenuates the postoperative inflammatory reaction. The effects of immunonutrition containing ...omega-3 FAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the inflammatory response to abdominal surgery continues to be unclear, although improved outcomes have been reported. Therefore, we determined the effectiveness of preoperatively initiated omega-3 FAs administration on postoperative inflammation defined as CRP (C-Reactive Protein), IL-6 (Interleukin 6), and WBC (White Blood Count) and potential effects on postoperative length of hospital stay (LOS) due to an improved inflammatory response.
a literature search of Cochrane Library was conducted to identify all randomized controlled trials (RCTs) investigating the effects of preoperatively initiated omega-3 to standard care, placebo, or other immunonutrients excluding omega-3 FAs in patients undergoing abdominal surgery until the end of December 2022.
a total of 296 articles were found during the initial search. Thirteen RCTs involving 950 patients were identified that met the search criteria. These were successively analyzed and included in this meta-analysis. There was no significant difference between the groups with respect to inflammatory markers IL-6: -0.55 -1.22; 0.12
= 0.10, CRP: -0.14 -0.67; 0.40
= 0.55, WBC: -0.58 -3.05; 1.89
0.42, or hospital stay -0.5 -1.43; 0.41
= 0.2.
although reduced inflammatory markers were observed, preoperative administration of omega-3 FAs immunonutrients had no significant effect on the postoperative inflammatory response in patients undergoing abdominal surgeries. Yet, results obtained from this study are inconclusive, likely attributed to the limited number of trials and patients included. Further studies are required to obtain a better educated verdict.
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