Background Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. Methods We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter and maintenance of glucose at a level between 180 and 200 mg per deciliter). Results At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa011300

Intensive Insulin Therapy in Critically Ill Patients

Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†.

In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC.

The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

 
| Classes of recommendations |
|:-------------------------- | ------------------------------------------------------------------------------------------------------------------------ |
| Class I | Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure |
|  Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy |
|  Class IIb | Usefulness/efficacy is less well established by evidence/opinion |
| Class III | Evidence or general agreement that the treatment or procedure is not useful/effective and, in some cases, may be harmful |

Diabetes and cardiovascular diseases (CVD) often appear …

/pdf/guidelines-on-diabetes-pre-diabetes-and-cardiovascular-4j63bs7fb2.pdf

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

https://www.focusopvoeding.nl/wp-content/uploads/2015/05/JAMDA-PROT-AGE-paperBauer.pdf

Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group

Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of immunosuppression that predisposes burn patients to infectious complications. A current summary of the classifications of burn wound infections, including their diagnosis, treatment, and prevention, is given. Early excision of the eschar has substantially decreased the incidence of invasive burn wound infection and secondary sepsis, but most deaths in severely burn-injured patients are still due to burn wound sepsis or complications due to inhalation injury. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis. The introduction of silver-impregnated devices (e.g., central lines and Foley urinary catheters) may reduce the incidence of nosocomial infections due to prolonged placement of these devices. Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.

Burn Wound Infections

Background:Optimization of postoperative outcome requires the application of evidence-based principles of care carefully integrated into a multimodal rehabilitation program.Objective:To assess, synthesize, and discuss implementation of “fast-track” recovery programs.Data Sources:Medline MBASE (Janua

Evidence-based surgical care and the evolution of fast-track surgery.

Background The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of β-adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns. Methods Twenty-five children with acute and severe burns (more than 40 percent of total body-surface area) were studied in a randomized trial. Thirteen received oral propranolol for at least two weeks, and 12 served as untreated controls. The dose of propranolol was adjusted to decrease the resting heart rate by 20 percent from each patient's base-line value. Resting energy expenditure and skeletal-muscle protein kinetics were measured before and after two weeks of beta-blockade (or no therapy, in controls). Body composition was measured serially throughout hospitalization. Results Patients in the control group and the propranolol group were similar with respect to age, weight, percentage of tota...

Reversal of catabolism by beta-blockade after severe burns.

Resistance exercise is a potent stimulator of muscle protein synthesis and muscle cell growth, with the increase in protein synthesis being detected within 2-3 h post-exercise and remaining elevated for up to 48 h. However, during exercise, muscle protein synthesis is inhibited. An increase in AMP-activated protein kinase (AMPK) activity has recently been shown to decrease mammalian target of rapamycin (mTOR) signalling to key regulators of translation initiation. We hypothesized that the cellular mechanism for the inhibition of muscle protein synthesis during an acute bout of resistance exercise in humans would be associated with an activation of AMPK and an inhibition of downstream components of the mTOR pathway (4E-BP1 and S6K1). We studied 11 subjects (seven men, four women) before, during, and for 2 h following a bout of resistance exercise. Muscle biopsy specimens were collected at each time point from the vastus lateralis. We utilized immunoprecipitation and immunoblotting methods to measure muscle AMPKalpha2 activity, and mTOR-associated upstream and downstream signalling proteins, and stable isotope techniques to measure muscle fractional protein synthetic rate (FSR). AMPKalpha2 activity (pmol min(-1) (mg protein)(-1)) at baseline was 1.7 +/- 0.3, increased immediately post-exercise (3.0 +/- 0.6), and remained elevated at 1 h post-exercise (P < 0.05). Muscle FSR decreased during exercise and was significantly increased at 1 and 2 h post-exercise (P < 0.05). Phosphorylation of 4E-BP1 at Thr37/46 was significantly reduced immediately post-exercise (P < 0.05). We conclude that AMPK activation and a reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle protein synthesis during resistance exercise. However, by 1-2 h post-exercise, muscle protein synthesis increased in association with an activation of protein kinase B, mTOR, S6K1 and eEF2.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2006.113175

Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle

Objective:To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial.Summary Background Data:A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with

/pdf/pathophysiologic-response-to-severe-burn-injury-41ppb3aqva.pdf

Pathophysiologic response to severe burn injury.

Persistence of muscle catabolism after severe burn

Preface. Chapter 1. Basic Characteristics of Isotopic Tracers. Chapter 2. Calculating Specific Activity and Radiation Dosages. Chapter 3. Calculation of Substance Kinetics: Single-Pool Model. Chapter 4. Calculation of Substrate Kinetics: Multiple-Pool Model. Chapter 5. Mass Spectrometry: Instrumentation. Chapter 6. Determination of Isotopic Enrichment. Chapter 7. Measurement of Substrate Oxidation. Chapter 8. Measurement of Total Energy Expenditure Using the Doubly Labeled Water Method. Chapter 9. Mass Isotopomer Distribution Analysis. Chapter 10. Glucose Metabolism. Chapter 11. Lipid Kinetics. Chapter 12. Whole Body Protein Synthesis and Breakdown. Chapter 13. Measurement of the Synthesis of Specific Proteins. Chapter 14. Measurement of Regional or Tissue Protein Breakdown. Chapter 15. Arterial-Venous Balance Technique to Measure Amino Acid Kinetics. Chapter 16. Nuclear Magnetic Resonance. Glossary. Abbreviations. Index.

David L. Chinkes

Papers

Reversal of catabolism by beta-blockade after severe burns.

Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle

Pathophysiologic response to severe burn injury.

Persistence of muscle catabolism after severe burn

Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis