Background
Since December 2019, an outbreak of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) initially emerged in Wuhan, China, and ...has spread worldwide now. Clinical features of patients with COVID-19 have been described. However, risk factors leading to in-hospital deterioration and poor prognosis in COVID-19 patients with severe disease have not been well identified.
Methods
In this retrospective, single-center cohort study, 1190 adult inpatients (≥ 18 years old) with laboratory-confirmed COVID-19 and determined outcomes (discharged or died) were included from Wuhan Infectious Disease Hospital from December 29, 2019 to February 28, 2020. The final follow-up date was March 2, 2020. Clinical data including characteristics, laboratory and imaging information as well as treatments were extracted from electronic medical records and compared. A multivariable logistic regression model was used to explore the potential predictors associated with in-hospital deterioration and death.
Results
1190 patients with confirmed COVID-19 were included. Their median age was 57 years (interquartile range 47–67 years). Two hundred and sixty-one patients (22%) developed a severe illness after admission. Multivariable logistic regression demonstrated that higher SOFA score (OR 1.32, 95% CI 1.22–1.43, per score increase,
p
< 0.001 for deterioration and OR 1.30, 95% CI 1.11–1.53, per score increase,
p
= 0.001 for death), lymphocytopenia (OR 1.81, 95% CI 1.13–2.89
p
= 0.013 for deterioration; OR 4.44, 95% CI 1.26–15.87,
p
= 0.021 for death) on admission were independent risk factors for in-hospital deterioration from not severe to severe disease and for death in severe patients. On admission D-dimer greater than 1 μg/L (OR 3.28, 95% CI 1.19–9.04,
p
= 0.021), leukocytopenia (OR 5.10, 95% CI 1.25–20.78), thrombocytopenia (OR 8.37, 95% CI 2.04–34.44) and history of diabetes (OR 11.16, 95% CI 1.87–66.57,
p
= 0.008) were also associated with higher risks of in-hospital death in severe COVID-19 patients. Shorter time interval from illness onset to non-invasive mechanical ventilation in the survivors with severe disease was observed compared with non-survivors (10.5 days, IQR 9.25–11.0 vs. 16.0 days, IQR 11.0–19.0 days,
p
= 0.030). Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39–6.01,
p
< 0.001). Administration of antiviral drugs especially oseltamivir or ganciclovir is associated with a decreased risk of death in severe patients (OR 0.17, 95% CI 0.05–0.64,
p
< 0.001).
Conclusions
High SOFA score and lymphocytopenia on admission could predict that not severe patients would develop severe disease in-hospital. On admission elevated D-dimer, leukocytopenia, thrombocytopenia and diabetes were independent risk factors of in-hospital death in severe patients with COVID-19. Administration of oseltamivir or ganciclovir might be beneficial for reducing mortality in severe patients.
Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical ...adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
Electrochemical incorporation reactions are ubiquitous in energy storage and conversion devices based on mixed ionic and electronic conductors, such as lithium-ion batteries, solid-oxide fuel cells ...and water-splitting membranes. The two-way traffic of ions and electrons across the electrochemical interface, coupled with the bulk transport of mass and charge, has been challenging to understand. Here we report an investigation of the oxygen-ion incorporation pathway in CeO2-δ (ceria), one of the most recognized oxygen-deficient compounds, during hydrogen oxidation and water splitting. We probe the response of surface oxygen vacancies, electrons and adsorbates to the electrochemical polarization at the ceria-gas interface. We show that surface oxygen-ion transfer, mediated by oxygen vacancies, is fast. Furthermore, we infer that the electron transfer between cerium cations and hydroxyl ions is the rate-determining step. Our in operando observations reveal the precise roles of surface oxygen vacancy and electron defects in determining the rate of surface incorporation reactions.
BackgroundImmune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also ...associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs.MethodsThis study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR025) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed statistically significant.ResultsA total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93–1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC025 = 2.49 and ROR025 = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55–1.83), ROR = 2.54 (95%CI 2.20–2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89–2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies.ConclusionOur pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice.
A thorough crash modeling effort was made to examine e-bicyclists’ injury severity, using a generalized ordered logit model, which can capture the ordinal nature of injury severity and allow for ...heterogeneity across observations. A number of factors associated with injury severity of e-bicyclists are identified, including older e-bicyclists, heavy truck involved, e-bicyclist at fault, e-bicyclist turn left, e-bicyclist cross the road, driver turn right, industrial area, weekday, and tree separation. Safety countermeasures and interventions are thus proposed based on the modeling results, including developing educational programs for specific age groups (e.g. older e-bicyclists, female e-bicyclists, and inexperienced drivers), launching safety campaigns, improving geometric design and traffic control in low-developed area, curve roads, and signalized intersections. Moreover, some interesting research topics are also suggested, such as examining head-on e-bike crash mechanism, crash mechanism between e-bicyclists and heavy trucks and motorcycles, and safety effects of different separation treatments on e-bicyclists’ injury severity from kinetic and kinematic perspectives.
Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. ...To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.
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► Building a new whole-genome SCS of high genome coverage, sensitivity, and specificity ► Whole-exome SCS of a typical JAK2-negative myeloproliferative neoplasm patient ► Depicting intratumoral genetics of the neoplasm at a single-cell nucleotide level ► Provision of evidence for monoclonal evolution of the neoplasm
A new high-throughput method based on non-PCR amplification allows whole-exome sequencing of single cells at the nucleotide level. Sequencing of 90 individual tumor cells from a JAK2-negative myeloproliferative neoplasm provides evidence for monoclonal evolution of the cancer.
Glycemic patterns have been reported to be prognostic factors for stroke; however, this remains to be further evaluated. This meta-analysis aimed to evaluate the usefulness of glycemic patterns such ...as persistent hyperglycemia (PH) including short duration and long duration PH (SPH; LPH), admission hyperglycemia (AH), short-duration hyperglycemia (SH), and persistent normoglycemia (PN) in predicting stroke prognosis using published results.
Major scientific databases including but are not limited to PubMed, EMBASE, Web of Science, Ovid, CNKI (Chinese National Knowledge Infrastructure), and Clinicaltrials.gov were searched till 1st March 2021 for clinical trials on the correlation between glycemic patterns and stroke outcomes. The primary outcome was defined as short-term (1- or 3-month) post-stroke mortality, and the secondary outcome was post-stroke hemorrhage at 6 months.
Ten studies involving 3584 individuals were included in the final analysis. In subgroup analyses, PH patients with no history of diabetes had increased post-stroke mortality (odds ratio OR: 4.80, 95% CI: 3.06-7.54) than patients with no PH; and patients with glucose levels > 140 mg/dl had greater mortality (OR: 5.12, 95% CI: 3.21-8.18) than those with glucose levels < 140 mg/dl; compared with AH patients, PH patients had increased short-term mortality (OR: 0.31, 95% CI: 0.16-0.60). In the prediction of stroke mortality among patients without diabetes, SPH (OR: 0.28, 95%CI: 0.12-0.69) seemed to be more related to increased mortality than LPH (OR: 0.35, 95% CI: 0.14--0.90).
PH, especially SPH, could predict increased post-stroke mortality in non-diabetic patients. The rank of individual glycemic patterns in predicting stroke mortality in non-diabetic patients was SPH > LPH > AH > PN.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•FRW contained higher OP levels and lower IP levels than TFW and FFW.•Some P fractions decreased after the regulation, mainly due to plant absorption.•Key environmental factors influencing P ...fractions during the regulation were revealed.•Eutrophication risk in estuarine wetlands might increase after the regulation.
To investigate the dynamics of phosphorus fractions and their influencing factors in the surface soils of estuarine wetlands experiencing different hydrological conditions before and after flow-sediment regulation, soil samples were collected in wetlands (tidal flooding wetlands (TFW), freshwater restoration wetlands (FRW) and freshwater flooding wetlands (FFW) of the Yellow River Estuary in each month from April to October of 2012. Our results showed that the average contents of organic phosphorus (OP) occurred in the following order: FRW soils (60.05 mg/kg) > TFW soils (38.72 mg/kg) > FFW soils (27.56 mg/kg), and accounted for less than 12% of total phosphorus (TP). In contrast to the pattern for OP, FRW soils contained lower inorganic phosphorus (IP) levels than TFW and FFW soils from April to August (p < 0.05). After the flow-sediment regulation, the TP, OP, moderately labile OP (ML-OP) ferrous/aluminum-bound IP (Fe/Al-P), and occluded IP (Oc-P) in the three wetlands decreased. The soluble and loosely bound IP (S/L-P) contents in TFW decreased, while the S/L-P contents in FRW soils increased. The levels of phosphorus fractions were affected by water and salt conditions, soil texture, exchangeable mineral element contents, and nutrient status. The Fe/Al-P and Oc-P in the three types of wetland soils were released, and the increase in S/L-P in FRW soils after the flow-sediment regulation might increase the risk of eutrophication in the coastal waters. The findings of this study could contribute to providing basic data regarding phosphorus fractions in different flooding estuarine wetlands of the Yellow River Estuary and guiding flow-sediment regulations and freshwater restoration to enhance the ecological functions of estuarine wetlands.
Background
Ventilator‐associated pneumonia (VAP) is common in intensive care units (ICUs). Some evidence indicates that probiotics may reduce the incidence of VAP. Several additional published ...studies have demonstrated that probiotics are safe and efficacious in preventing VAP in ICUs. We aimed to systematically summarise the results of all available data to generate the best evidence for the prevention of VAP.
Objectives
To evaluate the effectiveness and safety of probiotics for preventing VAP.
Search methods
We searched CENTRAL (2014, Issue 8), MEDLINE (1948 to September week 1, 2014) and EMBASE (2010 to September 2014).
Selection criteria
Randomised controlled trials (RCTs) comparing probiotics with placebo or another control (excluding RCTs that use probiotics in both study groups) to prevent VAP.
Data collection and analysis
Two review authors independently assessed eligibility and the quality of trials, and extracted data.
Main results
We included eight RCTs, with 1083 participants. All studies compared a form of probiotic (Lactobacillus casei rhamnosus; Lactobacillus plantarum; Synbiotic 2000FORTE; Ergyphilus; combination Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophilus) versus a control group (placebo; glutamine; fermentable fibre; peptide; chlorhexidine). The analysis of all RCTs showed that the use of probiotics decreased the incidence of VAP (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.52 to 0.95, low quality evidence). However, the aggregated results were uncertain for ICU mortality (OR 0.84, 95% CI 0.58 to 1.22 very low quality evidence), in‐hospital mortality (OR 0.78, 95% CI 0.54 to 1.14, very low quality evidence), incidence of diarrhoea (OR 0.72, 95% CI 0.47 to 1.09, very low quality evidence), length of ICU stay (mean difference (MD) ‐1.60, 95% CI ‐6.53 to 3.33, very low quality evidence), duration of mechanical ventilation (MD ‐6.15, 95% CI ‐18.77 to 6.47, very low quality evidence) and antibiotic use (OR 1.23, 95% CI 0.51 to 2.96, low quality evidence). Antibiotics for VAP were used for a shorter duration (in days) when participants received probiotics in one small study (MD ‐3.00, 95% CI ‐6.04 to 0.04). However, the CI of the estimated effect was too wide to exclude no difference with probiotics. There were no reported events of nosocomial probiotic infections in any included study.
The overall methodological quality of the included studies, based on our 'Risk of bias' assessments, was moderate with half of the included studies rated as a 'low' risk of bias; however, we rated four included studies as a 'high' risk of bias across one or more of the domains. The study limitations, differences in probiotics administered and participants, and small sample sizes across the included studies mean that the power to detect a trend of overall effect may be limited and chance findings cannot be excluded.
To explore the influence of some potential confounding factors in the studies, we conducted an intention‐to‐treat (ITT) analysis, which did not change the inference of per‐protocol analysis. However, our sensitivity analysis did not indicate a significant difference between groups for instances of VAP.
Authors' conclusions
Evidence suggests that use of probiotics is associated with a reduction in the incidence of VAP. However, the quality of the evidence is low and the exclusion of the one study that did not provide a robust definition of VAP increased the uncertainty in this finding. The available evidence is not clear regarding a decrease in ICU or hospital mortality with probiotic use. Three trials reported on the incidence of diarrhoea and the pooled results indicate no clear evidence of a difference. The results of this meta‐analysis do not provide sufficient evidence to draw conclusions on the efficacy and safety of probiotics for the prevention of VAP in ICU patients.
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