130 research outputs found
Machine learning identification of specific changes in myeloid cell phenotype during bloodstream infections
The early identification of bacteremia is critical for ensuring appropriate treatment of nosocomial infections in intensive care unit (ICU) patients. The aim of this study was to use flow cytometric data of myeloid cells as a biomarker of bloodstream infection (BSI). An eight-color antibody panel was used to identify seven monocyte and two dendritic cell subsets. In the learning cohort, immunophenotyping was applied to (1) control subjects, (2) postoperative heart surgery patients, as a model of noninfectious inflammatory responses, and (3) blood culture-positive patients. Of the complex changes in the myeloid cell phenotype, a decrease in myeloid and plasmacytoid dendritic cell numbers, increase in CD14(+)CD16(+) inflammatory monocyte numbers, and upregulation of neutrophils CD64 and CD123 expression were prominent in BSI patients. An extreme gradient boosting (XGBoost) algorithm called the “infection detection and ranging score” (iDAR), ranging from 0 to 100, was developed to identify infection-specific changes in 101 phenotypic variables related to neutrophils, monocytes and dendritic cells. The tenfold cross-validation achieved an area under the receiver operating characteristic (AUROC) of 0.988 (95% CI 0.985–1) for the detection of bacteremic patients. In an out-of-sample, in-house validation, iDAR achieved an AUROC of 0.85 (95% CI 0.71–0.98) in differentiating localized from bloodstream infection and 0.95 (95% CI 0.89–1) in discriminating infected from noninfected ICU patients. In conclusion, a machine learning approach was used to translate the changes in myeloid cell phenotype in response to infection into a score that could identify bacteremia with high specificity in ICU patients
First pilot trial of the STAR-Liege protocol for tight glycemic control in critically ill patients
peer reviewe
The first wave of COVID-19 in Intensive care
In December 2019, in Wuhan, a new human
infectious pathology was born, COVID-19, consisting
above all in pneumoniae, induced by the coronavirus
named SARS-CoV-2 because of the respiratory distress it
caused (SARS for severe acute respiratory syndrome, and
CoV for Coronavirus). A real health and planetary crisis
has appeared, much more substantial than that linked to
SARS-CoV-1 in 2002-2004 and to MERS-CoV (Middle East
Respiratory Syndrome Coronavirus) in 2012. In addition to
respiratory damage that can be dramatic, this pathology is
complicated by the frequency of cardiovascular, renal and
coagulation diseases. Health care systems have had to
adapt urgently, in the absence of hindsight from the patho- logy, and without effective therapeutic weapons. Through
this review of the literature, we detail our local practices for
the overall management of patients hospitalized in Intensive care
Preferential Localization of Human Origins of DNA Replication at the 5′-Ends of Expressed Genes and at Evolutionarily Conserved DNA Sequences
Replication of mammalian genomes requires the activation of thousands of
origins which are both spatially and temporally regulated by as yet unknown
mechanisms. At the most fundamental level, our knowledge about the
distribution pattern of origins in each of the chromosomes, among different
cell types, and whether the physiological state of the cells alters this
distribution is at present very limited.We have used standard λ-exonuclease resistant nascent DNA preparations in
the size range of 0.7–1.5 kb obtained from the breast cancer cell line
MCF–7 hybridized to a custom tiling array containing 50–60 nt
probes evenly distributed among genic and non-genic regions covering about
1% of the human genome. A similar DNA preparation was used for
high-throughput DNA sequencing. Array experiments were also performed with
DNA obtained from BT-474 and H520 cell lines. By determining the sites
showing nascent DNA enrichment, we have localized several thousand origins
of DNA replication. Our major findings are: (a) both array and DNA
sequencing assay methods produced essentially the same origin distribution
profile; (b) origin distribution is largely conserved (>70%) in
all cell lines tested; (c) origins are enriched at the 5′ends of
expressed genes and at evolutionarily conserved intergenic sequences; and
(d) ChIP on chip experiments in MCF-7 showed an enrichment of H3K4Me3 and
RNA Polymerase II chromatin binding sites at origins of DNA replication.Our results suggest that the program for origin activation is largely
conserved among different cell types. Also, our work supports recent studies
connecting transcription initiation with replication, and in addition
suggests that evolutionarily conserved intergenic sequences have the
potential to participate in origin selection. Overall, our observations
suggest that replication origin selection is a stochastic process
significantly dependent upon local accessibility to replication factors
Corticosteroids are associated with a decrease in mortality in a multicenter cohort of mechanically ventilated COVID-19 patients.
Endothelial intric oxide synthase in the cardiomyocyte : modulatory roles on contractility and cell biology
Selective myocyte eNOS overexpression improves the sympathovagal balance of the heart and protects it against excessive beta-adrenegic stimulation, in part through potentiation of vagal inhibition of cardiac contraction and prevention of ectopic contractions.
Benefit of eNOS overexpression can further be extended on cardiac stem cells, with a favorable role of eNOS on their transdifferentiation and possibly on their survival through an anti-apopotic effect.
Finally, cardioprotective drugs such as statins and insulin precisely increase myocyte eNOS expression. This observation links well-known unexplained pleiotropic effects to a potential powerful mechanism, i.e. an increase of endogenous myocyte eNOS expression and activity.
Myocyte eNOS can be considered as an "endogenous b-blocker" for the heart. It is also a key protein in the survival response of the cardiomyocyte, working in conjunction with others (e.g. PKB, insulin), even able to promote cardiac regeneration. Finally, myocyte eNOS is a common effector of many cardioprotective drugs or even assist device, and its preservation in patients could prevent their evolution to cardiac decompensation.(SBIM 3)--UCL, 200
Role of platelet activating factor and its antagonists in bronchial asthma
Inhalation of the platelet activating factor (PAF) produces symptoms of bronchial asthma, a disease in which PAF plays an important role. This lipid mediator released by many kinds of cells exerts its effects on blood cells and on cells of the bronchial wall both directly and indirectly. The crucial role played by PAF in the inflammatory cascades explains the current interest in specific PAF antagonists. These antagonists have both bronchodilator and anti-inflammatory properties and act simultaneously as beta-adrenoceptor agonists and corticosteroids. The first clinical trials of PAF antagonists in the treatment of resistant asthma have given results that are interesting but not superior to those obtained with the conventional anti-asthmatic drugs. The indications for PAF antagonists combined with other specific antagonists will soon be determined
Incidence and risk factors for early renal dysfunction after liver transplantation.
peer reviewedAIM: To determine renal dysfunction post liver transplantation, its incidence and risk factors in patients from a Belgian University Hospital. METHODS: Orthotopic liver transplantations performed from January 2006 until September 2012 were retrospectively reviewed (n = 187). Patients with no renal replacement therapy (RRT) before transplantation were classified into four groups according to their highest creatinine plasma level during the first postoperative week. The first group had a peak creatinine level below 12 mg/L, the second group between 12 and 20 mg/L, the third group between 20 and 35 mg/L, and the fourth above 35 mg/L. In addition, patients who needed RRT during the first week after transplantation were also classified into the fourth group. Perioperative parameters were recorded as risk factors, namely age, sex, body mass index (BMI), length of preoperative hospital stay, prior bacterial infection within one month, preoperative ascites, preoperative treatment with beta-blocker, angiotensin-converting enzyme inhibitor or non steroidal anti-inflammatory drugs, preoperative creatinine and bilirubin levels, donor status (cardiac death or brain death), postoperative lactate level, need for intraoperative vasopressive drugs, surgical revision, mechanical ventilation for more than 24 h, postoperative bilirubin and transaminase peak levels, postoperative hemoglobin level, amount of perioperative blood transfusions and type of immunosuppression. Univariate and multivariate analysis were performed using logistic ordinal regression method. Post hoc analysis of the hemostatic agent used was also done. RESULTS: There were 78 patients in group 1 (41.7%), 46 in group 2 (24.6%), 38 in group 3 (20.3%) and 25 in group 4 (13.4%). Twenty patients required RRT: 13 (7%) during the first week after transplantation. Using univariate analysis, the severity of renal dysfunction was correlated with presence of ascites and prior bacterial infection, preoperative bilirubin, urea and creatinine level, need for surgical revision, use of vasopressor, postoperative mechanical ventilation, postoperative bilirubin and urea, aspartate aminotransferase (ASAT), and hemoglobin levels and the need for transfusion. The multivariate analysis showed that BMI (OR = 1.1, P = 0.004), preoperative creatinine level (OR = 11.1, P < 0.0001), use of vasopressor (OR = 3.31, P = 0.0002), maximal postoperative bilirubin level (OR = 1.44, P = 0.044) and minimal postoperative hemoglobin level (OR = 0.059, P = 0.0005) were independent predictors of early post-liver transplantation renal dysfunction. Neither donor status nor ASAT levels had significant impact on early postoperative renal dysfunction in multivariate analysis. Absence of renal dysfunction (group 1) was also predicted by the intraoperative hemostatic agent used, independently of the extent of bleeding and of the preoperative creatinine level. CONCLUSION: More than half of receivers experienced some degree of early renal dysfunction after liver transplantation. Main predictors were preoperative renal dysfunction, postoperative anemia and vasopressor requirement
Réanimation métabolique du myocarde: à la redécouverte de l’insuline
info:eu-repo/semantics/publishe
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