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Background & Aims: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay., Methods: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality., Results: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m 2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%., Conclusion: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy., Methods: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed., Findings: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups., Interpretation: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm., Funding: Programme Hospitalier de Recherche Clinique., Competing Interests: Declaration of interests The authors declare no competing interests. The AKIKI 2 trial was promoted by the Assistance Publique—Hôpitaux de Paris and funded by a grant of the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2016; AOM16278)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

During exercise, there is an increase in amino acid (AA) oxidation accompanied by a depression in whole-body protein synthesis and an increase in protein breakdown. Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements. When investigating the effects of AA on the control of muscle protein synthesis (MPS), we showed that increased availability of mixed AAs caused a rise in human MPS to about the same extent as complete meals. Leucine alone (and to some extent other essential, but not nonessential, AAs) can stimulate MPS for a short period, suggesting that leucine acts as a signal as well as a substrate. MPS stimulation by infused AAs shows tachyphylaxis, returning to basal rates after 2 h, possibly explaining why chronically elevated leucine delivery does not elevate MPS clinically. Increased availability of essential amino acids (EAAs) results in dose-related responses of MPS, but, in elderly subjects, there is blunted sensitivity and responsiveness associated with decreased total RNA and mRNA for signaling proteins and signaling activity. Increases of MPS due to EAAs are associated with elevation of signaling activity in the mammalian target of rapamycin (mTOR)/p70 ribosomal subunit S6 kinase eukaryotic initiation factor 4 binding protein 1 pathway, without requiring rises of plasma insulin availability above 10 microU/mL. However, at insulin of <5 microU/mL, AAs appear to stimulate MPS without increasing mTOR signaling. Further increasing availability of insulin to postprandial values increases signaling activity, but has no further effect on MPS.

The components of the stimulatory effect of food on net deposition of protein are beginning to be identified and separated. One of the most important of these appears to be the effect of amino acids per se in stimulating muscle anabolism. Amino acids appear to have a linear stimulatory effect within the range of normal diurnal plasma concentrations from postabsorptive to postprandial. Within this range, muscle protein synthesis (measured by incorporation of stable isotope tracers of amino acids into biopsied muscle protein) appears to be stimulated approximately twofold; however, little further increase occurs when very high concentrations of amino acids (>2.5 times the normal postabsorptive plasma concentration) are made available. Amino acids provided in surfeit of the ability of the system to synthesize protein are disposed of by oxidation, ureagenesis and gluconeogenesis. The stimulatory effect of amino acids appears to be time dependent; a square wave increase in the availability of amino acids causes muscle protein synthesis to be stimulated and to fall back to basal values, despite continued amino acid availability. The relationship between muscle protein synthesis and insulin availability suggests that most of the stimulatory effects occur at low insulin concentrations, with large increases having no effect. These findings may have implications for our understanding of the body's requirements for protein. The maximal capacity for storage of amino acids as muscle protein probably sets an upper value on the extent to which amino acids can be stored after a single meal.

Background: Recombinant human insulin-like growth factor-I (rhIGF-I) accelerates recovery from acute renal failure (ARF) in rats. IGF-I acts through the IGF-I receptor (IGF-IR) and its actions may be modified by IGF-I binding proteins (IGFBPs). It therefore would be of value to determine the effects of both ARF and rhIGF-I treatment on serum IGFBPs and mRNA for IGFBPs and IGF-IR., Methods: Rats with ARF and sham-operated control rats were randomized to receive rhIGF-I or vehicle injections thrice daily for 72 to 74 hours starting five hours after surgery. Serum IGFPBs 1 to 6 were measured serially, and mRNA for IGFBPs 1 to 6 and for IGF-IR were measured in several tissues obtained 72 to 74 hours after surgery., Results: At 72 to 74 hours, serum IGFBP-1 and IGFBP-2 levels were higher in rhIGF-I treated rats. Serum IGFBP-3 was affected by both ARF and rhIGF-I. IGFBP-4 rose transiently only in ARF groups. At 72 to 74 hours, mRNA for several IGFBPs was reduced in renal cortex of ARF rats. Low mRNA for IGFBP-4 and -6 was observed in renal medulla of the ARF rats, particularly in comparison to the sham-operated rats receiving vehicle. Renal medullary IGFBP-2 mRNA was decreased in ARF and sham rats given rhIGF-I as compared to sham animals given vehicle. Hepatic IGFBP-2 mRNA was higher in both rhIGF-I treated groups versus those given vehicle. Otherwise, there were no differences in IGFBP mRNAs among the four groups in lung, heart, and skeletal muscle. IGF-IR mRNA was decreased in renal cortex and medulla of both ARF groups and was not detected in liver in any group., Conclusions: Thus, ARF and rhIGF-I treatment each affected certain serum IGFBPs and jointly affected some IGFBPs. ARF suppressed gene transcription for renal cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2 mRNA and serum IGFBP-2. These effects of ARF or rhIGF-I may influence rhIGF-I actions in rats with ischemic ARF.