Background
Higher expression of olfactomedin‐4 (OLFM4), a gene regulated by nuclear factor‐kappa B (NF‐κB), has been related to a higher risk of organ failure and death in patients with septic shock. ...We aimed to evaluate the association between OLFM4 single nucleotide polymorphisms (SNPs) and septic shock‐related death in 175 patients who underwent major surgery, as well as its performance in predicting mortality.
Materials and methods
We carried out a retrospective study. A total of seven OLFM4 SNPs were genotyped by Agena Bioscience's MassARRAY platform. Statistical analysis was performed by Kaplan‐Meier and Cox regression tests. The diagnostic performance for predicting septic shock‐related death was evaluated by the area under the receiver‐operating characteristic (AUROC) curve.
Results
Patients with rs17552047 A allele and rs1891944 TT genotype had higher survival than patients with rs17552047 G allele (P‐value = .024) and patients with rs1891944 CC/CT genotype (P‐value = .038). However, only rs17552047 was associated with a lower risk of death under an additive inheritance model (adjusted hazard ratio aHR = 0.44, 95% CI = 0.27‐0.71). The multivariate model with the most significant clinical variables (lactate, chronic kidney disease, peritonitis, heart disease and elective surgery) showed an AUROC of 0.776 for predicting septic shock‐related death. When we added the OLFM4 rs17552047 SNP to the previous model, the AUROC was 0.811 and was close to reaching significant differences with the previous model (P‐value = .065).
Conclusion
OLFM4 rs17552047 A allele predicts septic shock survival in patients who underwent major surgery. Furthermore, rs17552047, together with clinical variables, could be useful to predict the outcome of septic shock.
Background
The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in ...hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease.
Methods
An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups.
Results
One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years,
p
= 0.005) and had higher frequency of fever (96.6 vs. 78.7%,
p
= 0.036) and anosmia (48.3% vs. 22.7%,
p
= 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL,
p
= 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL,
p
= 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL,
p
= 0.071).
Conclusions
The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.
Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The ...progressive increase of both the incidence and prevalence of sepsis has translated into a significant socioeconomic burden for health systems. Currently, it is the leading cause of noncoronary mortality worldwide and represents one of the most prevalent pathologies both in hospital emergency services and in intensive care units. In this article, we review the role of both endothelial dysfunction and neutrophil dysregulation in the physiopathology of this disease. The lack of a key symptom in sepsis makes it difficult to obtain a quick and accurate diagnosis of this condition. Thus, it is essential to have fast and reliable diagnostic tools. In this sense, the use of biomarkers can be a very important alternative when it comes to achieving these goals. Both new biomarkers and treatments related to endothelial dysfunction and neutrophil dysregulation deserve to be further investigated in order to open new venues for the diagnosis, treatment and prognosis of sepsis.
Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a ...massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease.
Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test.
Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules’ levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 μM) as an independent risk factor for 28-day intubation/death in COVID-19 patients OR: 2.57; 95% CI: 1.10–5.99; p = 0.029. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 μM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p < 0.001).
These findings deepen our knowledge of oxidative stress status in SARS-CoV-2 infection, supporting its important role in COVID-19. In fact, higher lipid peroxidation levels are independently associated to a higher risk of intubation or death at 28 days in COVID-19 patients.
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•Antioxidant enzymes and oxidative cell damage levels were significantly higher while total antioxidant capacity was lower in COVID-19 patients.•Only lipid peroxidation was statistically different across COVID-19 severity.•Lipid peroxidation levels over 1948.17 μM are an independent risk factor for 28-day intubation/death in COVID-19 patients.•COVID-19 patients showing lipid peroxidation levels above 1948.17 μM were intubated or died 8.4 days earlier on average.
Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not ...well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996;
= 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999;
= 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110;
= 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986;
= 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193;
= 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.
Non-alcoholic fatty liver disease (NAFLD) is characterised by an excess of hepatic fat that can progress to steatohepatitis, fibrosis, cirrhosis and hepatocarcinoma. The imbalance between lipid ...uptake/lipogenesis and lipid oxidation/secretion in the liver is a major feature of NAFLD. Given the lack of a non-invasive and reliable methods for the diagnosis of non-alcoholic steatohepatitis (NASH), it is important to find serum markers that are capable of discriminating or defining patients with this stage of NASH. Blood samples were obtained from 152 Caucasian subjects with biopsy-proven NAFLD due to persistently elevated liver enzyme levels. Metabolites representative of oxidative stress were assessed. The findings derived from this work revealed that NAFLD patients with a NASH score of ≥ 4 showed significantly higher levels of lipid peroxidation (LPO). Indeed, LPO levels above the optimal operating point (OOP) of 315.39 μM are an independent risk factor for presenting a NASH score of ≥ 4 (OR: 4.71; 95% CI: 1.68−13.19; p = 0.003). The area under the curve (AUC = 0.81, 95% CI = 0.73−0.89, p < 0.001) shows a good discrimination ability of the model. Therefore, understanding the molecular mechanisms underlying the basal inflammation present in these patients is postulated as a possible source of biomarkers and therapeutic targets in NASH.
Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity ...of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank:
= 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665),
< 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878),
= 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.
Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We ...prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95–6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07–1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39–0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.
Scope
The intake of food rich in polyphenols is related to a lower incidence in almost all chronic degenerative diseases. However, relatively little is known about the molecular mechanisms involved ...in its antioxidant properties. The aim of this study was to determine whether the mechanism of action of polyphenols could be related to a modulation in energy uptake and metabolism, and further induced mitochondrial changes.
Methods and results
For this purpose, male C57BL6 mice were fed during 3 months with a tea‐based beverage rich in polyphenols. Insulin sensitivity, tissue oxidative damage biomarkers, as well as energy‐related signaling pathways were determined to evaluate its mechanism of action. As a result, a tissue‐ and protein‐specific subtle reduction in oxidative damage was observed. Skeletal muscle showed mitochondrial changes in respiratory complexes and an increase in AMP‐activated protein kinase α levels, suggesting reduced energy availability. These changes were also associated with adipose tissue cellular metabolism. This was confirmed by a decline in the potential of energy uptake, evidenced by a diminished intestinal and systemic absorption of carbohydrates together with an inhibition of insulin sensitivity.
Conclusions
Our results suggest that the mechanisms of action of green tea polyphenols may be related to their ability to modulate energy uptake leading to mitochondrial adaptations possibly responsible for the changes in protein oxidative damage.
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