Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest

Background: Physical inactivity is often associated with positive energy balance and fat gain. Objective: We aimed to assess whether energy intake in excess of requirement activates systemic inflammation and antioxidant defenses and accelerates muscle atrophy induced by inactivity. Design: Nineteen healthy male volunteers were studied before and at the end of 5 wk of bed rest. Subjects were allowed to spontaneously adapt to decreased energy requirement (study A, n = 10) or were provided with an activity-matched diet (study B, n = 9). Groups with higher (HEB) or lower (LEB) energy balance were identified according to median values of inactivity-induced changes in fat mass (\u394FM, assessed by bioelectrical impedance analysis). Results: In pooled subjects (n = 19; median \u394FM: 1.4 kg), bed rest-mediated decreases in fat-free mass (bioelectrical impedance analysis) and vastus lateralis thickness (ultrasound imaging) were significantly greater (P < 0.03) in HEBAB (-3.8 \ub1 0.4kg and -0.32 \ub1 0.04 cm, respectively) than in LEBab (-2.3 \ub1 0.5 kg and -0.09 \ub1 0.04 cm, respectively) subjects. In study A (median \u394FM: 1.8 kg), bed rest-mediated increases in plasma leptin, C-reactive protein, and myeloperoxidase were greater (P < 0.04) in HEBA than in LEBA subjects. Bed rest-mediated changes of glutathione synthesis rate in eythrocytes (L-[3,3-2H2]cysteine incorporation) were greater (P = 0.03) in HEBA (from 70 \ub1 19 to 164 \ub1 29%/d) than in LEBA (from 103 \ub1 23 to 84 \ub1 27%/d) subjects. Conclusions: Positive energy balance during inactivity is associated with greater muscle atrophy and with activation of systemic inflammation and of antioxidant defenses. Optimizing caloric intake may be a useful strategy for mitigating muscle loss during period of chronic inactivity

Metabolic and nutritional support of critically ill patients: consensus and controversies.

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines.

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access

Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial

Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used

Identification of a novel coronavirus in patients with severe acute respiratory syndrome

BACKGROUND: The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. METHODS: Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. RESULTS: A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. CONCLUSIONS: The novel coronavirus might have a role

Does Intensive Insulin Therapy Reduce the Severity of Organ Failure?

Organ failure is a common complication associated with increased mortality in intensive care units (ICUs) patients. Increased mortality is also associated with hyperglycemia and glycemic variability. This research evaluates the impact of an intensive vs. a conventional insulin therapy on organ failures

Insulin Sensitivity, Its Variability and Glycemic Outcome: A model-based analysis of the difficulty in achieving tight glycemic control in critical care

(invited)Effective tight glycemic control (TGC) can improve outcomes in intensive care unit (ICU) patients, but is difficult to achieve consistently. Glycemic level and variability, particularly early in a patient’s stay, are a function of variability in insulin sensitivity/resistance resulting from the level and evolution of stress response, and are independently associated with mortality. This study examines the daily evolution of variability of insulin sensitivity in ICU patients using patient data (N = 394 patients, 54019 hours) from the SPRINT TGC study. Model-based insulin sensitivity (SI) was identified each hour and hour-to-hour percent changes in SI were assessed for Days 1-3 individually and Day 4 Onward, as well as over all days. Cumulative distribution functions (CDFs), median values, and inter-quartile points (25th and 75th percentiles) are used to assess differences between groups and their evolution over time. Compared to the overall (all days) distributions, ICU patients are more variable on Days 1 and 2 (p < 0.0001), and less variable on Days 4 Onward (p < 0.0001). Day 3 is similar to the overall cohort (p = 0.74). Absolute values of SI start lower and rise for Days 1 and 2, compared to the overall cohort (all days), (p < 0.0001), are similar on Day 3 (p = .72) and are higher on Days 4 Onward (p < 0.0001). ICU patients have lower insulin sensitivity (greater insulin resistance) and it is more variable on Days 1 and 2, compared to an overall cohort on all days. This is the first such model-based analysis of its kind. Greater variability with lower SI early in a patient’s stay greatly increases the difficulty in achieving and safely maintaining glycemic control, reducing potential positive outcomes. Clinically, the results imply that TGC patients will require greater measurement frequency, reduced reliance on insulin, and more explicit specification of carbohydrate nutrition in Days 1-3 to safely minimise glycemic variability for best outcome