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.
Display omitted
•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.
Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with ...sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO
) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO
is associated with risk of death in adult patients with sepsis/septic shock after major surgery.
We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO
> 100 mmHg (n = 216), or PaO
≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation.
In patients with PaO
≤ 100 mmHg, we found prolonged mechanical ventilation (2 8 vs. 1 4 days, p < 0.001), higher ICU stay (8 13 vs. 5 9 days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 3 vs. 7 5, p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% 88 vs. 25.5% 55, p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded.
Oxygenation with a PaO
above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO
in postsurgical patients with severe infections.
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.
Abstract Background Sepsis is strongly associated with an increased risk of postoperative mortality, longer length of hospital stay, and elevated health care costs. Early clinical symptoms overlap ...with those of systemic inflammatory response syndrome, a response that commonly occurs after cardiac surgery with cardiopulmonary bypass. Since a combination of biomarkers has been demonstrated to improve the prediction of postoperative infection, the objective of the present study was to test whether the combination of C-reactive protein (CRP), white blood cells (WBC), and procalcitonin (PCT) is able to predict postoperative infection in a large cohort of cardiac surgery patients. Material and methods Case-control study involving 423 patients who underwent cardiac surgery with cardiopulmonary bypass. Patients were retrospectively classified into two groups based on whether they developed severe sepsis or septic shock during the postoperative period. Blood samples for biological measurements (PCT, CRP, and WBC) were drawn on the first day in the intensive care unit, then once daily in the morning until the 10th postoperative day. Results CRP median values were similar in both groups. WBC and PCT median values were significantly higher in patients with infection than without during the first 10 postoperative days. With elevation cutoffs ≤3 times (OR: 4.058; 95% CI: 2.206-7.463; P = 0.001) and ≥4 times (OR: 10.274, 95% CI: 3.690-28.604; P < 0.001), the median value for PCT (1.7 ng/mL) and/or WBC (13,000 cells/mm3 ) on the second postoperative day was significantly associated with the development of infection. Conclusions The goal of this study was to use a large cohort of cardiac surgery patients to ensure that the results were representative of this population. The combination of PCT and WBC levels over the first three postoperative days was able to predict postoperative infection within the 30 d following cardiac surgery.
Background
High cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine ...profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients.
Methods
Serum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients.
Results
At day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p<0.001).
Conclusions
Hypercytokinemia is a hallmark of COVID-19 but relevant differences between survivors and non-survivors can be early observed. Combinatorial analysis of serum cytokines and chemokines can contribute to mortality risk assessment and optimize therapeutic strategies. Three clusters of cytokines have been identified as independent markers or risk factors of COVID mortality.
Elderly people who reside in long-term care facilities form a frail and vulnerable population, with multiple pathologies and high percentages of cognitive and functional disability.
The aims of this ...study were to assess the safety of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in frail nursing home residents and to evaluate its effectiveness 6 months after full vaccination.
This was an ambispective observational study.
Residents of a long-term care facility in Madrid, Spain.
One hundred and thirty-seven nursing home residents (81.8% female, mean age 87.77 ± 8.31 years) with high comorbidity (61.3% Charlson Index ≥ 3) and frailty (75% Clinical Frail Scale ≥ 7) who received the BNT162B2 mRNA vaccine.
Safety data were collected to evaluate the type of adverse drug reactions and their duration, severity, and causality. Immunogenicity was tested 6 months after the primary vaccination and effectiveness was evaluated by the incidence of SARS-CoV-2 infection, the number of hospital admissions, and mortality due to coronavirus disease 2019 (COVID-19).
Safety: Of the residents, 21.9% had some adverse reaction and 5.8% had a severe or more serious adverse reaction. The most frequent adverse reactions were fatigue (13.1%), pyrexia (12.4%), and headache (7.3%). No association was observed between frailty (including a need for palliative care) and clinical, functional or cognitive status of the participants and the occurrence of adverse events. Immunogenicity and Effectiveness: After 6 months of vaccination, only one case of SARS-CoV-2 infection was confirmed in the vaccinated residents. Most of the nursing home residents presented positive serology (95.2%). Loss of immunogenicity was associated with older age (95.12 ± 3.97 vs. 87.24 ± 8.25 years; p = 0.03) and no previous COVID-19 infection (16.6% vs. 70%; p < 0.001). Binary logistic regression models did not reveal this association.
The BNT162B2 vaccine is well tolerated and effective in nursing home residents, independently of their clinical, functional, cognitive, or frailty characteristics. For the most part, immunogenicity has been maintained over time, regardless of comorbidity, functional status or frailty.
The DUF642 protein family is found exclusively in spermatophytes and is represented by 10 genes in Arabidopsis and in most of the 24 plant species analyzed to date. Even though the primary structure ...of DUF642 proteins is highly conserved in different spermatophyte species, studies of their expression patterns in Arabidopsis have shown that the spatial-temporal expression pattern for each gene is specific and consistent with the phenotypes of the mutant plants studied so far. Additionally, the regulation of DUF642 gene expression by hormones and environmental stimuli was specific for each gene, showing both up- and down-regulation depending of the analyzed tissue and the intensity or duration of the stimuli. These expression patterns suggest that the DUF642 genes are involved throughout the development and growth of plants. In general, changes in the expression patterns of DUF642 genes can be related to changes in pectin methyl esterase activity and/or to changes in the degree of methyl-esterified homogalacturonans during plant development in different cell types. Thus, the regulation of pectin methyl esterases mediated by DUF642 genes could contribute to the regulation of the cell wall properties during plant growth.
Respiratory viruses are part of the normal microbiota of the respiratory tract, which sometimes cause infection with/without respiratory insufficiency and the need for hospital or ICU admission. The ...aim of this study is to determine the prevalence of respiratory viruses in nontransplanted postoperative septic patients as well as lymphocyte count influence in their presence and its relationship to mortality. 223 nontransplanted postsurgical septic patients were recruited on the Intensive Care Unit (ICU) at Hospital Clínico Universitario de Valladolid prior to the SARS-COV-2 pandemic. Patients were split into 2 groups according to the presence/absence of respiratory viruses. Multivariate logistic regression analysis was used to identify independent factors related to positive respiratory virus PCR test. Respiratory viruses were isolated in 28.7% of patients. 28-day mortality was not significantly different between virus-positive and virus-negative groups. Logistic regression analysis revealed that lymphocyte count ≤ 928/µl is independently associated with a positive PCR result OR 3.76, 95% CI (1.71-8.26), P = .001 adjusted by platelet count over 128,500/µL OR 4.27, 95% CI (1.92-9.50) P < .001 and the presence of hypertension OR 2.69, 95% CI (1.13-6.36) P = .025 as confounding variables. Respiratory viruses' detection by using PCR in respiratory samples of nontransplanted postoperative septic patients is frequent. These preliminary results revealed that the presence of lymphopenia on sepsis diagnosis is independently associated to a positive virus result, which is not related to a higher 28-day mortality.
The potential of photodynamic therapy (PDT) applications is based primarily on the selection of suitable photosensitizers (PSs). However, highly efficient PSs producing singlet oxygen and other ...reactive oxygen species (ROS) often have poor water solubility and tend to aggregate in biological media. The most common alternative strategy to address the solubility of PSs is based on difficult-to-control encapsulation or conjugation to liposomes, micelles, or other nanoparticles
via
surface non-covalent interactions. Covalent functionalization remains relatively unexplored for common PSs. Here, we report a strategy to use highly efficient but poorly water-soluble BODIPY PSs connected to the surface of nitrogen-doped graphene quantum dots (NGQDs) through controlled covalent functionalization. These NGQD-BODIPY PSs do not aggregate in aqueous solutions and generate ROS upon irradiation with visible light, with singlet-oxygen production quantum yields up to 83%.
In vitro
fluorescence bioimaging was used to confirm that the PSs reside mostly in the cytoplasmic region of human cervical cancer cells (HeLa), and the system reduced the cell viability by ∼85% upon irradiation.
Water-soluble photosensitizers based on covalently grafted nitrogen-doped graphene quantum dot-BODIPY for cellular imaging and photodynamic therapy.
As the global urgency for effective antimicrobial agents intensifies, this work harnesses the widely demonstrated antimicrobial activity of silver nanoparticles (Ag-NPs) and proposes alternative ...synthesis approaches to metal–organic hybrid systems with antimicrobial activity. In this study, the proposed synthesis route involves decorating metallic nanoparticles into organic substrates without previous doping. The synthesis simultaneously uses polyethylene glycol for three crucial purposes: (1) acting as a mild reducing agent to generate Ag-NPs with a spherical shape and diameters ranging from 10 to just over 20 nm, (2) functioning as a dispersing agent for flakes of commercial nanostructured carbon supports, including reduced graphene oxide (rGO, ID-nano), and commercial carbon nanoplatelets from Sigma-Aldrich (GNPs, Sigma-Aldrich), and (3) serving as a promoter for the homogeneous anchoring of Ag-NPs in the carbon lattice without altering the conformation of the carbon lattice. This intricate interaction involves the π-orbitals from the sp2 hybridization honeycomb and the d-orbitals from the Ag-NPs, leading to the constructive rehybridization of rGO and GNPs. In our study, Ag-NPs/rGO are compared with a support lacking oxygenated groups in the lattice, such as commercial GNPs (Sigma-Aldrich), to produce Ag-NPs/GNPs. This comparison maintains constructive sp2 rehybridization, preserving the characteristic properties of rGO (ID-nano) and graphene nanoplatelets, including commercial GNPs (Sigma-Aldrich). Notably, oxygenated groups from rGO exhibit greater availability for exchanging oxo and hydroxy defects for Ag-NPs compared with GNPs (Sigma-Aldrich). The resulting Ag-NPs/rGO and Ag-NPs/GNP systems are thoroughly physicochemically characterized, employing techniques such as Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, and scanning transmission electron microscopy, revealing the successful integration of Ag-NPs with minimal alteration to the carbon lattice. Subsequent antimicrobial evaluation against Escherichia coli (E. coli) demonstrates significant activity, with Ag-NPs/rGO and Ag-NPs/GNPs registering similar minimum inhibitory concentrations of 50 μg mL–1. This study underscores the potential of our metal–organic hybrid systems as antimicrobial agents and provides insights into the constructive rehybridization process, paving the way for diverse applications in the biomedical and environmental fields.
PDF
