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BACKGROUND: Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS: Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS: Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P

Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of 'neuropathy', 'myopathy', 'neuromyopathy', or 'weakness' with 'critical illness', 'critically ill', 'ICU', 'PICU', 'sepsis' or 'burn'. ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs., Author(s): Ilse Vanhorebeek [sup.1], Nicola Latronico [sup.2] [sup.3], Greet Van den Berghe [sup.1] Author Affiliations: (1) grid.5596.f, 0000 0001 0668 7884, Clinical Division and Laboratory of Intensive Care Medicine, Department [...]

This article tells the story of our long search for the answer to one question: Is stress hyperglycemia in critically ill patients adaptive or maladaptive? Our earlier work had suggested the lack of hepatic insulin effect and hyperglycemia as jointly predicting poor outcome. Therefore, we hypothesized that insulin infusion to reach normoglycemia, tight glucose control, improves outcome. In three randomized controlled trials (RCTs), we found morbidity and mortality benefit with tight glucose control. Moving from the bed to the bench, we attributed benefits to the prevention of glucose toxicity in cells taking up glucose in an insulin-independent, glucose concentration gradient–dependent manner, counteracted rather than synergized by insulin. Several subsequent RCTs did not confirm benefit, and the large Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation, or "NICE-SUGAR," trial found increased mortality with tight glucose control associated with severe hypoglycemia. Our subsequent clinical and mechanistic research revealed that early use of parenteral nutrition, the context of our initial RCTs, had been a confounder. Early parenteral nutrition (early-PN) aggravated hyperglycemia, suppressed vital cell damage removal, and hampered recovery. Therefore, in our next and largest "TGC-fast" RCT, we retested our hypothesis, without the use of early-PN and with a computer algorithm for tight glucose control that avoided severe hypoglycemia. In this trial, tight glucose control prevented kidney and liver damage, though with much smaller effect sizes than in our initial RCTs without affecting mortality. Our quest ends with the strong recommendation to omit early-PN for patients in the ICU, as this reduces need of blood glucose control and allows cellular housekeeping systems to play evolutionary selected roles in the recovery process. Once again, less is more in critical care. [ABSTRACT FROM AUTHOR]

Purpose Early diagnosis of acute kidney injury (AKI) remains a major challenge. We developed and validated AKI prediction models in adult ICU patients and made these models available via an online prognostic calculator. We compared predictive performance against serum neutrophil gelatinase-associated lipocalin (NGAL) levels at ICU admission. Methods Analysis of the large multicenter EPaNIC database. Model development (n = 2123) and validation (n = 2367) were based on clinical information available (1) before and (2) upon ICU admission, (3) after 1 day in ICU and (4) including additional monitoring data from the first 24 h. The primary outcome was a comparison of the predictive performance between models and NGAL for the development of any AKI (AKI-123) and AKI stages 2 or 3 (AKI-23) during the first week of ICU stay. Results Validation cohort prevalence was 29% for AKI-123 and 15% for AKI-23. The AKI-123 model before ICU admission included age, baseline serum creatinine, diabetes and type of admission (medical/surgical, emergency/planned) and had an AUC of 0.75 (95% CI 0.75-0.75). The AKI-23 model additionally included height and weight (AUC 0.77 (95% CI 0.77-0.77)). Performance consistently improved with progressive data availability to AUCs of 0.82 (95% CI 0.82-0.82) for AKI-123 and 0.84 (95% CI 0.83-0.84) for AKI-23 after 24 h. NGAL was less discriminant with AUCs of 0.74 (95% CI 0.74-0.74) for AKI-123 and 0.79 (95% CI 0.79-0.79) for AKI-23. Conclusions AKI can be predicted early with models that only use routinely collected clinical information and outperform NGAL measured at ICU admission. The AKI-123 models are available at http://akipredictor.com/. Trial registration Clinical Trials.gov NCT00512122, Author(s): Marine Flechet [sup.1], Fabian Güiza [sup.1], Miet Schetz [sup.1], Pieter Wouters [sup.1], Ilse Vanhorebeek [sup.1], Inge Derese [sup.1], Jan Gunst [sup.1], Isabel Spriet [sup.2], Michaël Casaer [sup.1], Greet Van [...]