Background
There is no consensus on the management of anticoagulation during extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high rate of hemostatic complications, ...possibly associated with inadequate monitoring of heparin anticoagulation. This study aims to assess the safety and feasibility of an anticoagulation protocol for patients undergoing ECMO based on thromboelastography (TEG) as opposed to an activated partial thromboplastin time (aPTT)-based protocol.
Methods
We performed a multicenter, randomized, controlled trial in two academic tertiary care centers. Adult patients with acute respiratory failure treated with veno-venous ECMO were randomized to manage heparin anticoagulation using a TEG-based protocol (target 16–24 min of the R parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5–2 of aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the study protocol.
Results
Forty-two patients were enrolled: 21 were randomized to the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two groups (9 (7–16) days in the TEG group and 11 (4–17) days in the aPTT group,
p
= 0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7 (9.5–15.3) IU/kg/h vs. 15.7 (10.9–21.3) IU/kg/h, respectively,
p
= 0.03). Safety parameters, assessed as number of hemorrhagic or thrombotic events and transfusions given, were not different between the two study groups. As for the feasibility, the TEG-based protocol triggered heparin infusion rate adjustments more frequently (
p
< 0.01) and results were less frequently in the target range compared to the aPTT-based protocol (
p
< 0.001). Number of prescribed TEG or aPTT controls (according to study groups) and protocol violations were not different between the study groups.
Conclusions
TEG seems to be safely used to guide anticoagulation management during ECMO. Its use was associated with the administration of lower heparin doses compared to a standard of care aPTT-based protocol.
Trial registration
ClinicalTrials.gov, October 22,2014. Identifier: NCT02271126.
Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron ...balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person's r correlation coefficient = - 0.34), log-hepcidin and log-ERFE (r = - 0.47), and log-hepcidin and sTfR (r = - 0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype-phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease.
To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders.
This was an ...observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates.
Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected.
IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to assess the condylar volume in adult patients with different skeletal classes and vertical patterns using cone-beam computed tomography (CBCT). CBCT scans of 146 condyles ...from 73 patients (mean age 30 ± 12 years old; 49 female, 24 male) were selected from the archive of the Department of Dentistry and Maxillofacial Surgery of Fondazione IRCCS Ca' Granda, Milan, Italy, and retrospectively analyzed. The following inclusion criteria were used: adult patients; CBCT performed with the same protocol (0.4 mm slice thickness, 16 × 22 cm field of view, 20 s scan time); no systemic diseases; and no previous orthodontic treatments. Three-dimensional cephalometric tracings were performed for each patient, the mandibular condyles were segmented and the relevant volumes calculated using Mimics Materialize 20.0
software (Materialise, Leuven, Belgium). Right and left variables were analyzed together using random-intercept linear regression models. No significant association between condylar volumes and skeletal class was found. On the other hand, in relation to vertical patterns, the mean values of the mandibular condyle volumes in hyperdivergent subjects (688 mm
) with a post-rotation growth pattern (625 mm
) were smaller than in hypodivergent patients (812 mm
) with a horizontal growth pattern (900 mm
). Patients with an increased divergence angle had smaller condylar volumes than subjects with normal or decreased mandibular plane divergence. This relationship may help the clinician when planning orthodontic treatment.
Night and shift work might be risk factors for metabolic and cardiovascular disorders due to interference with diet, circadian metabolic rhythms, and lifestyle. The relationship between permanent ...night work and metabolic and cardiovascular risk factors was explored in a retrospective longitudinal study of workers employed in a large municipal enterprise in charge of street cleaning and domestic waste collection. All subjects who had worked night shifts between 1976 and 2007 as hand sweepers, motor sweepers, and delivery tricar drivers were compared with subjects who always worked the same jobs but on day shifts. From the periodical medical surveillance files, we identified 488 male workers who had been examined on average five times (minimum 2, maximum 14) during the study period, for a total of 2,328 medical examinations; 157 always had worked day shifts, 12 always the night shift, and 319 both (initially day and subsequently night shifts). Their age ranged from 22 to 62 yrs, and work experience varied from 1 to 28 yrs. Lifestyle habits (smoking, alcohol consumption), body mass index, serum glucose, total cholesterol, tryglicerides, hepatic enzymes, blood pressure, resting electrocardiogram, diabetes, coronary heart disease, hypertension, and related drugs were taken into consideration for the analysis. We used generalized estimating equations (GEE) models (exchangeable correlation matrix) to analyze the relationship between night work and health effects while accounting for within-subject correlations and adjusting for study period, job, age, and lifestyle variables. As a whole, night workers smoked more and had significantly higher BMI, serum total cholesterol, and triglycerides than day workers. Both the inter-individual comparison between day and night workers and the intra-individual comparison among the workers, who were day workers at the beginning of their employment and later became night workers, showed a significant increase in BMI, total cholesterol, and tryglicerides associated with night work. No consistent effect was seen on fasting glucose, hepatic enzymes, and blood pressure, whereas a higher incidence of coronary heart disease was recorded in night workers.
Abstract
Veno-venous Extracorporeal Membrane Oxygenation (ECMO) is used in the most severe cases of respiratory failure and further exacerbates the patients’ inflammatory status. Antithrombin is ...supplemented during ECMO for its anticoagulant effects, but it also deploys anti-inflammatory properties. In this pre-specified ancillary study of the GATRA trial NCT03208270 we aimed to evaluate the relationship between antithrombin and inflammation during ECMO. Forty-six patients were included in the study, 23 were randomized to receive antithrombin to maintain a level of 80–120% (study group) and 23 were randomized not to be supplemented (control group). Anticoagulation was provided in both groups with heparin infusion. Six cytokines were measured at 5 timepoints from prior to ECMO start to 7 days after ECMO removal. Cytokines decreased during the study but overall were not very different in the two groups. Testing the interaction between the study group and timepoints suggests that the administration of antithrombin led to a more rapid decrease over time of IL-6, IL-1β, TNF-⍺ and Pro-ADM. Plasma levels of antithrombin (either endogenous or exogenous) were negatively associated with all cytokines. Inflammation decreases during ECMO but a causal effect of antithrombin administration on the reduction of inflammation (and its clinical relevance) must be confirmed by appropriately powered studies.
Objectives
Right ventricular outflow tract abnormalities (RVOTA) have been mostly reported in recipient twins (RT) of monochorionic/diamniotic (MC/DA) twin pregnancies with twin‐to‐twin transfusion ...syndrome (TTTS). Aim of the study was to describe RVOTA detected in MC/DA pregnancies without TTTS.
Methods
Cases of RVOTA were retrieved from our database among all MC/DA pregnancies without TTTS from 2009 to 2018.
Results
Out of 891 MC/DA twin pregnancies without TTTS, 14 (1.6%) were associated with RVOTA: 10 pulmonary stenosis (PS), one steno‐insufficiency, one insufficiency and two atresia (PA). In 93% of cases (13/14), pregnancy was complicated either by amniotic fluid discrepancy (AFD) or by TAPS or mostly by selective fetal growth restriction (sFGR) (11/13: 85%), involving predominantly (10/11: 91%) the large twin, with high incidence (9/11: 82%) of sFGR and AFD coexistence. Eight out of 14 (57%) survived after the perinatal period (7 PS, 1 PA). Five (62%) underwent pulmonary balloon valvuloplasty, whereas 3 children still showed persistent mild PS at cardiac follow up after 1 year of life.
Conclusions
RVOTA can occur in MC/DA pregnancies without TTTS, particularly when other complications coexist. In complicated cases specialized fetal echocardiographic evaluation is recommended during pregnancy; RVOTA cases should be delivered in a tertiary level center, where cardiologists are available.
Key points
What is already known about this topic?
Right ventricular outflow tract abnormalities (RVOTA) is the typical cardiac abnormality of recipient twin in monocorionic/diamniotic (MC/DA) pregnancies complicated by twin‐to‐twin transfusion syndrome (TTTS)
RVOTA has been sporadically reported in (MC/DA) not complicated by TTTS
What does this study add?
This is the largest reported cohort of RVOTA cases in MC/DA without TTTS
RVOTA are more represented in pregnancies with a coexistence of complications such as sFGR and amniotic fluid discordance
Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained ...obscure.
We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change >1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p = 0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.
Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified ...point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality.
This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge.
UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93-0.98, p = 0.003).
Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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