Organ Support Therapy in the Intensive Care Unit and Return to Work in Out-of-Hospital Cardiac Arrest Survivors:a Nationwide Cohort Study

AIM: With increased survival after out-of-hospital cardiac arrest (OHCA), impact of the post-resuscitation course has become important. Among 30-day OHCA survivors, we investigated associations between organ support therapy in the Intensive Care Unit (ICU) and return to work.METHODS: This Danish nationwide cohort-study included 30-day-OHCA-survivors who were employed prior to arrest. We linked OHCA data to information on in-hospital care and return to work. For patients admitted to an ICU and based on renal replacement therapy (RRT), cardiovascular support and mechanical ventilation, we assessed the prognostic value of organ support therapies in multivariable Cox regression models.RESULTS: Of 1,087 30-day survivors, 212 (19.5%) were treated in an ICU with 0-1 types of organ support, 494 (45.4%) with support of two organs, 26 (2.4%) with support of three organs and 355 (32.7%) were not admitted to an ICU. Return to work increased with decreasing number of organs supported, from 53.8% (95% CI: 49.5-70.1%) in patients treated with both RRT, cardiovascular support and mechanical ventilation to 88.5% (95% CI: 85.1-91.8%) in non-ICU-patients. In 732 ICU-patients, ICU-patients with support of 3 organs had significantly lower adjusted hazard ratios (HR) of returning to work (0.50 [95% CI: 0.30-0.85] compared to ICU-patients with support of 0-1 organ. The corresponding HR was 0.48 [95% CI: 0.30-0.78] for RRT alone.CONCLUSIONS: In 30-day survivors of OHCA, number of organ support therapies and in particular need of RRT were associated with reduced rate of return to work, although more than half of these latter patients still returned to work.</p

High-resolution ex vivo magnetic resonance angiography: a feasibility study on biological and medical tissues

<p>Abstract</p> <p>Background</p> <p>In biomedical sciences, ex vivo angiography is a practical mean to elucidate vascular structures three-dimensionally with simultaneous estimation of intravascular volume. The objectives of this study were to develop a magnetic resonance (MR) method for ex vivo angiography and to compare the findings with computed tomography (CT). To demonstrate the usefulness of this method, examples are provided from four different tissues and species: the human placenta, a rice field eel, a porcine heart and a turtle.</p> <p>Results</p> <p>The optimal solution for ex vivo MR angiography (MRA) was a compound containing gelatine (0.05 g/mL), the CT contrast agent barium sulphate (0.43 mol/L) and the MR contrast agent gadoteric acid (2.5 mmol/L). It was possible to perform angiography on all specimens. We found that ex vivo MRA could only be performed on fresh tissue because formalin fixation makes the blood vessels permeable to the MR contrast agent.</p> <p>Conclusions</p> <p>Ex vivo MRA provides high-resolution images of fresh tissue and delineates fine structures that we were unable to visualise by CT. We found that MRA provided detailed information similar to or better than conventional CTA in its ability to visualize vessel configuration while avoiding interfering signals from adjacent bones. Interestingly, we found that vascular tissue becomes leaky when formalin-fixed, leading to increased permeability and extravascular leakage of MR contrast agent.</p

Thermodynamics of Heat Shock Response

Production of heat shock proteins are induced when a living cell is exposed to a rise in temperature. The heat shock response of protein DnaK synthesis in E.coli for temperature shifts from temperature T to T plus 7 degrees, respectively to T minus 7 degrees is measured as function of the initial temperature T. We observe a reversed heat shock at low T. The magnitude of the shock increases when one increase the distance to the temperature $T_0 \approx 23^o$, thereby mimicking the non monotous stability of proteins at low temperature. Further we found that the variation of the heat shock with T quantitatively follows the thermodynamic stability of proteins with temperature. This suggest that stability related to hot as well as cold unfolding of proteins is directly implemented in the biological control of protein folding. We demonstrate that such an implementation is possible in a minimalistic chemical network.Comment: To be published in Physical Review Letter

Incidence of Atrial Fibrillation in Patients with either Heart Failure or Acute Myocardial Infarction and Left Ventricular Dysfunction: A Cohort Study

<p>Abstract</p> <p>Background</p> <p>We examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction. Patients either had a recent myocardial infarction (with or without clinical heart failure) or symptomatic heart failure (without a recent MI). Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months.</p> <p>Methods</p> <p>The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies included 2627 patients without atrial fibrillation at baseline, who were randomised to treatment with either dofetilide or placebo.</p> <p>Results</p> <p>The competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6% in the placebo-treated heart failure-group, and 2.9% in the placebo-treated myocardial infarction-group.</p> <p>Cox proportional hazard regression found a 42% significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo (hazard ratio 0.58, 95% confidence interval 0.40-0.82) and there was no interaction with study (p = 0.89).</p> <p>In the heart failure-group, the incidence of atrial fibrillation was significantly reduced to 5.6% in the dofetilide-treated patients (hazard ratio 0.57, 95% confidence interval 0.38-0.86).</p> <p>In the myocardial infarction-group the incidence of atrial fibrillation was reduced to 1.7% with the administration of dofetilide. This reduction was however not significant (hazard ratio 0.61, 95% confidence interval 0.30-1.24).</p> <p>Conclusion</p> <p>In patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6% in patients with heart failure and 2.9% in patients with a recent MI. Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure. The reduction in the subgroup with recent MI was not statistically significant, but the hazard ratio was similar to the hazard ratio for the heart failure patients, and there was no difference between the effect in the two studies (p = 0.89 for interaction).</p

Translation Representations and Scattering By Two Intervals

Studying unitary one-parameter groups in Hilbert space (U(t),H), we show that a model for obstacle scattering can be built, up to unitary equivalence, with the use of translation representations for L2-functions in the complement of two finite and disjoint intervals. The model encompasses a family of systems (U (t), H). For each, we obtain a detailed spectral representation, and we compute the scattering operator, and scattering matrix. We illustrate our results in the Lax-Phillips model where (U (t), H) represents an acoustic wave equation in an exterior domain; and in quantum tunneling for dynamics of quantum states

GLUT4 and UBC9 Protein Expression Is Reduced in Muscle from Type 2 Diabetic Patients with Severe Insulin Resistance

Subgroups of patients with type 2 diabetes mellitus demand large insulin doses to maintain euglycemia. These patients are characterized by severe skeletal muscle insulin resistance and the underlying pathology remains unclear. The purpose of this study was to examine protein expression of the principal glucose transporter, GLUT4, and associated proteins in skeletal muscle from type 2 diabetic patients characterized by severe insulin resistance.Seven type 2 diabetic patients with severe insulin resistance (mean insulin dose 195 IU/day) were compared with seven age matched type 2 diabetic patients who did not require insulin treatment, and with an age matched healthy control group. Protein expression of GLUT4 and associated proteins was assessed in muscle and fat biopsies using standard western blotting techniques.GLUT4 protein expression was significantly reduced by ∼30 pct in skeletal muscle tissue from severely insulin resistant type 2 diabetic subjects, compared with both healthy controls and type 2 diabetic subjects that did not require insulin treatment. In fat tissue, GLUT4 protein expression was reduced in both diabetic groups. In skeletal muscle, the reduced GLUT4 expression in severe insulin resistance was associated with decreased ubiquitin-conjugating enzyme 9 (UBC9) expression while expression of GLUT1, TBC1D1 and AS160 was not significantly different among type 2 diabetic patients and matched controls.Type 2 diabetic patients with severe insulin resistance have reduced expression of GLUT4 in skeletal muscle compared to patients treated with oral antidiabetic drugs alone. GLUT4 protein levels may therefore play a role in the pathology behind type 2 diabetes mellitus among subgroups of patients, and this may explain the heterogeneous response to insulin treatment. This new finding contributes to the understanding of the underlying mechanisms for the development of extreme insulin resistance