Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination.

OBJECTIVE: Most of the available clinical tests for prognosis of post-anoxic coma are informative of poor outcome. Previous work has shown that an improvement in auditory discrimination over the first days of coma is predictive of awakening. Here, we aimed at evaluating this test on a large cohort of patients undergoing therapeutic hypothermia and at investigating its added value on existing clinical measures. METHODS: We recorded electroencephalography responses to auditory stimuli in 94 comatose patients, under hypothermia and after re-warming to normal temperature. Auditory discrimination was semi-automatically quantified by decoding electroencephalography responses to frequently repeated vs. rare sounds. Outcome prediction was based on the change of decoding performance from hypothermia to normothermia. RESULTS: An increase in auditory discrimination from hypothermia to normothermia was observed for 33 out of 94 patients. Among them, 27 awoke from coma, resulting in a positive predictive value of awakening of 82% (95% confidence interval: 0.65-0.93). Most non-survivors showing an improvement in auditory discrimination had incident status epilepticus. By excluding them, 27 out of 29 patients with improvement in auditory discrimination survived, resulting in a considerable improvement of the predictive value for awakening (93%, with 95% confidence interval: 0.77-0.99). Importantly, this test predicted the awakening of 13 out of 51 patients for which the outcome was uncertain based on current tests. INTERPRETATION: The progression of auditory discrimination from hypothermia to normothermia has a high predictive value for awakening. This quantitative measure provides an added value to existing clinical tests and encourages the maintenance of life support. This article is protected by copyright. All rights reserved

Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood

Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients

Hyperglycemic Myocardial Damage Is Mediated by Proinflammatory Cytokine: Macrophage Migration Inhibitory Factor

Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation.83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose.Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells.Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2

Impact of adiposity on cardiac structure in adult life: the Childhood Determinants of Adult Health (CDAH) study.

BACKGROUND: We have examined the association between adiposity and cardiac structure in adulthood, using a life course approach that takes account of the contribution of adiposity in both childhood and adulthood. METHODS: The Childhood Determinants of Adult Health study (CDAH) is a follow-up study of 8,498 children who participated in the 1985 Australian Schools Health and Fitness Survey (ASHFS). The CDAH follow-up study included 2,410 participants who attended a clinic examination. Of these, 181 underwent cardiac imaging and provided complete data. The measures were taken once when the children were aged 9 to 15 years, and once in adult life, aged 26 to 36 years. RESULTS: There was a positive association between adult left ventricular mass (LVM) and childhood body mass index (BMI) in males (regression coefficient (β) 0.41; 95% confidence interval (CI): 0.14 to 0.67; p = 0.003), and females (β = 0.53; 95% CI: 0.34 to 0.72; p < 0.001), and with change in BMI from childhood to adulthood (males: β = 0.27; 95% CI: 0.04 to 0.51; p < 0.001, females: β = 0.39; 95% CI: 0.20 to 0.58; p < 0.001), after adjustment for confounding factors (age, fitness, triglyceride levels and total cholesterol in adulthood). After further adjustment for known potential mediating factors (systolic BP and fasting plasma glucose in adulthood) the relationship of LVM with childhood BMI (males: β = 0.45; 95% CI: 0.19 to 0.71; p = 0.001, females: β = 0.49; 95% CI: 0.29 to 0.68; p < 0.001) and change in BMI (males: β = 0.26; 95% CI: 0.04 to 0.49; p = 0.02, females: β = 0.40; 95% CI: 0.20 to 0.59; p < 0.001) did not change markedly. CONCLUSIONS: Adiposity and increased adiposity from childhood to adulthood appear to have a detrimental effect on cardiac structure

(704) Interamnia: a transitional object between a dwarf planet and a typical irregular-shaped minor body

Context. With an estimated diameter in the 320–350 km range, (704) Interamnia is the fifth largest main belt asteroid and one of the few bodies that fills the gap in size between the four largest bodies with D > 400 km (Ceres, Vesta, Pallas and Hygiea) and the numerous smaller bodies with diameter ≤200 km. However, despite its large size, little is known about the shape and spin state of Interamnia and, therefore, about its bulk composition and past collisional evolution. Aims. We aimed to test at what size and mass the shape of a small body departs from a nearly ellipsoidal equilibrium shape (as observed in the case of the four largest asteroids) to an irregular shape as routinely observed in the case of smaller (D ≤ 200 km) bodies. Methods. We observed Interamnia as part of our ESO VLT/SPHERE large program (ID: 199.C-0074) at thirteen different epochs. In addition, several new optical lightcurves were recorded. These data, along with stellar occultation data from the literature, were fed to the All-Data Asteroid Modeling algorithm to reconstruct the 3D-shape model of Interamnia and to determine its spin state. Results. Interamnia’s volume-equivalent diameter of 332 ± 6 km implies a bulk density of ρ = 1.98 ± 0.68 g cm−3, which suggests that Interamnia – like Ceres and Hygiea – contains a high fraction of water ice, consistent with the paucity of apparent craters. Our observations reveal a shape that can be well approximated by an ellipsoid, and that is compatible with a fluid hydrostatic equilibrium at the 2σ level. Conclusions. The rather regular shape of Interamnia implies that the size and mass limit, under which the shapes of minor bodies with a high amount of water ice in the subsurface become irregular, has to be searched among smaller (D ≤ 300 km) less massive (m ≤ 3 × 1019 kg) bodies

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]