Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have ...better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).
We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.
A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 95% CI 1.214-4.314, p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 95% CI 1.018-1.104, p = 0.005) or MP referenced to PBW (HR 1.004 95% CI 1.002-1.007, p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H
O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H
O) (63.6% vs. 29.7%, p < 0.001).
MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, ...modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells. Keywords: Colon cancer, SERPINE1, Tumor microenvironment, Tumor-infiltrating immune cells
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxidative stress is considered a key factor contributing to the initiation and development of cardiac injury following ischaemia‒reperfusion (I/R). Arachidonate 5-lipoxygenase (ALOX5) is a ...rate-limiting enzyme for leukotriene biosynthesis. MK-886 is an inhibitor of ALOX5 that exhibits anti-inflammatory and antioxidant activities. However, the significance of MK-886 in preventing I/R-mediated cardiac injury and the underlying mechanism remain unclear. Cardiac I/R model was produced by ligation/release of the left anterior descending artery. MK-886 (20 mg/kg) was administered intraperitoneally into mice at 1 and 24 h before I/R. Our results indicated that MK-886 treatment significantly attenuated I/R-mediated cardiac contractile dysfunction and decreased the infarct area, myocyte apoptosis, and oxidative stress accompanied with reduction of Kelch-like ECH-associated protein 1 (keap1) and upregulation of nuclear factor erythroid 2-related factor 2 (NRF2). Conversely, administration of the proteasome inhibitor epoxomicin and NRF2 inhibitor ML385 greatly abrogated MK-886-mediated cardioprotection after I/R injury. Mechanistically, MK-886 enhanced the expression of the immunoproteasome subunit β5i, which interacted with keap1 and enhanced its degradation, leading to activation of the NRF2-dependent antioxidant response and improvement of mitochondrial fusion-fission balance in the I/R-treated heart. In summary, our present findings indicated that MK-886 could protect the heart against I/R injury and highlight that MK-886 may represent a promising therapeutic candidate for preventing ischaemic disease.
Many methods have been developed for analyzing survival data which are commonly right-censored. These methods, however, are challenged by complex features pertinent to the data collection as well as ...the nature of data themselves. Typically, biased samples caused by left-truncation (or length-biased sampling) and measurement error often accompany survival analysis. While such data frequently arise in practice, little work has been available to simultaneously address these features. In this paper, we explore valid inference methods for handling left-truncated and right-censored survival data with measurement error under the widely used Cox model. We first exploit a flexible estimator for the survival model parameters which does not require specification of the baseline hazard function. To improve the efficiency, we further develop an augmented nonparametric maximum likelihood estimator. We establish asymptotic results and examine the efficiency and robustness issues for the proposed estimators. The proposed methods enjoy appealing features that the distributions of the covariates and of the truncation times are left unspecified. Numerical studies are reported to assess the finite sample performance of the proposed methods.
Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia ...condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on the regulation of IL-8 by an intermittent hypoxic culture system. The secreted protein and mRNA levels were studied by means of enzyme-linked immunosorbent assay and RT/real-time PCR. The chemotactic migration of monocytes toward a conditioned medium containing IL-8 was performed by means of the transwell filter migration assay. Peripheral venous blood was collected from 31 adult OSA patients and RNA was extracted from the monocytes for the analysis of IL-8 expression. The result revealed that intermittent hypoxia enhanced the monocytic THP-1 cells to actively express IL-8 at both the secreted protein and mRNA levels, which subsequently increased the migration ability of monocytes toward IL-8. The ERK, PI3K and PKC pathways were demonstrated to contribute to the activation of IL-8 expression by intermittent hypoxia. In addition, increased monocytic IL-8 expression was found in OSA patients, with disease severity dependence and diurnal changes. This study concluded the monocytic IL-8 gene expression can be activated by intermittent hypoxia and increased in OSA patients.
Death in intensive care units (ICUs) may increase bereaved family members' risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) ...and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care.
In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient's ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling.
The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio 95% confidence interval = 1.036 1.006, 1.066), financial insufficiency (3.166 1.159, 8.647), and reported use of pain medications (3.408 1.230, 9.441) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 0.911, 0.965) and having a Do-Not-Resuscitate (DNR) order issued before the patient's death (0.073 0.011, 0.490) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members' satisfaction with end-of-life care (0.988 0.944, 1.034) or decision-making in ICUs (0.980 0.944, 1.018).
The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The risk of pregnancy and neonatal complications in women with PCOS is debatable. In order to determine ...the risk of pregnancy and neonatal complications, evidence regarding these risks was examined.
Literature searches were performed in the electronic databases MEDLINE, EMBASE, and CENTRAL based on the established strategy and eligible tries were included according to inclusion and exclusion criteria. A systematic literature review looking at rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia, premature delivery, neonatal birth weight, caesarean section and admission to a neonatal intensive care unit (NICU) was conducted in women with PCOS. Pregnancy outcomes between women with PCOS versus controls were included. Sensitivity analyses were performed to determine the reliability of the available evidence and to validate the results. The study was performed with the approval of the ethics committee of the First Affiliated Hospital of Guangxi Medical University.
A total of 27studies, involving 4982 women with PCOS and 119692 controls were eligible for the meta-analysis. Women with PCOS demonstrated a significantly higher risk of developing GDM (OR3.43; 95% CI: 2.49-4.74), PIH (OR3.43; 95% CI: 2.49-4.74), preeclampsia (OR2.17; 95% CI: 1.91-2.46), preterm birth (OR1.93; 95%CI: 1.45-2.57), caesarean section (OR 1.74; 95% CI: 1.38-2.11) compared to controls. Their babies had a marginally significant lower birth weight (WMD -0.11g; 95%CI: -0.19 - -0.03), and higher risk of admission to NICU (OR 2.32; 95% CI: 1.40-3.85) compared to controls.
Women with PCOS have increased risk of adverse pregnancy and neonatal complications. It is necessary to establish guidelines for supervision during pregnancy and parturition to prevent these complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper, we introduce the R package NetDA, which aims to deal with multiclassification with network structures in predictors accommodated. To address the natural feature of network structures, ...we apply Gaussian graphical models to characterize dependence structures of the predictors and directly estimate the precision matrix. After that, the estimated precision matrix is employed to linear discriminant functions and quadratic discriminant functions. The R package NetDA is now available on CRAN, and the demonstration of functions is summarized as a vignette in the online documentation.
In this paper, we mainly discuss the cure model with survival data. Different from the usual survival data with right-censoring, we incorporate the features of left-truncation and measurement error ...in covariates. Generally speaking, left-truncation causes a biased sample in survival analysis; measurement error in covariates may incur a tremendous bias if we do not deal with it properly. To deal with these challenges, we propose a flexible way to analyze left-truncated survival data and correct measurement error in covariates. The theoretical results are also established in this paper.
Cardiac ischaemia/reperfusion (I/R) injury causes cardiomyocyte apoptosis and mitochondrial dysfunction. Ursolic acid (UA), as a pentacyclic triterpenoid carboxylic acid, exerts several bioactivities ...in animal models of different diseases, but the preventive role of UA in I/R-induced myocardial dysfunction remains largely unknown. Male wild-type mice were pre-administered with UA at a dosage of 80 mg/kg i.p. and then subjected to cardiac I/R injury for 24 h. Cardiac function and pathological changes were examined by echocardiography and histological staining. The protein and mRNA levels of the genes were determined using qPCR and immunoblotting analysis. Our results revealed that UA administration in mice significantly attenuated the I/R-induced decline in cardiac function, infarct size, myocyte apoptosis, and oxidative stress. Mechanistically, UA increased three immunoproteasome catalytic subunit expressions and activities, which promoted ubiquitinated PP2A degradation and activated AMPK-PGC1α signalling, leading to improved mitochondrial biosynthesis and dynamic balance. In vitro experiments confirmed that UA treatment prevented hypoxia/reperfusion (H/R)-induced cardiomyocyte apoptosis and mitochondrial dysfunction through activation of AMPK signalling. In summary, our findings identify UA as a new activator of the immunoproteasome that exerts a protective role in I/R-induced myocardial dysfunction and suggest that UA supplementation could be beneficial for the prevention of cardiac ischaemic disease.
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