Assessment of physiological barriers to nutrition following critical illness

Abstract not available.James Whitehead, Matthew J. Summers, Rhea Louis, Luke M. Weinel, Kylie Lange, Bethany Dunn, Marianne J. Chapman, Lee-anne S. Chappl

Incident diabetes in survivors of critical illness and mechanisms underlying persistent glucose intolerance: a prospective cohort study

OBJECTIVES:Stress hyperglycemia occurs in critically ill patients and may be a risk factor for subsequent diabetes. The aims of this study were to determine incident diabetes and prevalent prediabetes in survivors of critical illness experiencing stress hyperglycemia and to explore underlying mechanisms. DESIGN:This was a prospective, single center, cohort study. At admission to ICU, hemoglobin A1c was measured in eligible patients. Participants returned at 3 and 12 months after ICU admission and underwent hemoglobin A1c testing and an oral glucose tolerance test. Blood was also collected for hormone concentrations, whereas gastric emptying was measured via an isotope breath test. β-cell function was modeled using standard techniques. SETTING:Tertiary-referral, mixed medical-surgical ICU. PATIENTS:Consecutively admitted patients who developed stress hyperglycemia and survived to hospital discharge were eligible. MEASUREMENTS AND MAIN RESULTS:Consent was obtained from 40 patients (mean age, 58 yr [SD, 10], hemoglobin A1c 36.8 mmol/mol [4.9 mmol/mol]) with 35 attending the 3-month and 26 the 12-month visits. At 3 months, 13 (37%) had diabetes and 15 (43%) had prediabetes. At 12 months, seven (27%) participants had diabetes, whereas 11 (42%) had prediabetes. Mean hemoglobin A1c increased from baseline during the study: +0.7 mmol/mol (-1.2 to 2.5 mmol/mol) at 3 months and +3.3 mmol/mol (0.98-5.59 mmol/mol) at 12 months (p = 0.02). Gastric emptying was not significantly different across groups at either 3 or 12 months. CONCLUSIONS:Diabetes and prediabetes occur frequently in survivors of ICU experiencing stress hyperglycemia. Based on the occurrence rate observed in this cohort, structured screening and intervention programs appear warranted.Palash Kar, Mark P. Plummer, Yasmine Ali Abdelhamid, Emma J. Giersch, Matthew J. Summers, Luke M. Weinel ... et al

Muscle size, strength, and physical function in response to augmented calorie delivery: A TARGET sub-study.

Purpose Augmented calories may attenuate muscle loss experienced in critical illness. This exploratory sub-study assessed the effect of augmented calorie delivery on muscle mass, strength, and function. Materials and methods Patients in The Augmented versus Routine approach to Giving Energy Trial (TARGET) randomised to 1.5 kcal/ml or 1.0 kcal/ml enteral formulae at a single-centre were included. Ultrasound-derived muscle layer thickness (MLT) at quadriceps, forearm and mid-upper arm, and handgrip strength, were measured weekly from baseline to hospital discharge, and 3- and 6-months. Physical function was assessed at 3- and 6-months using the 'get up and go' and 6-min walk tests. Data are mean ± SD. Results Eighty patients were recruited (1.5 kcal: n = 38, 58 ± 14y, 60%M, APACHE II 20 ± 7; 1.0 kcal: n = 42, 54 ± 18y, 66%M, APACHE II 22 ± 10). The 1.5 kcal/ml group received more calories with no difference in quadriceps MLT at any timepoint including ICU discharge (primary outcome) (2.90 ± 1.27 vs 2.39 ± 1.06 cm; P = 0.141). Relationships were similar for all MLT measures, handgrip strength, and 6-min walk test. Patients in the 1.5 kcal/ml group had improved 'get up and go' test at 3-months (6.66 ± 1.33 vs. 9.11 ± 2.94 s; P = 0.014). Conclusion Augmented calorie delivery may not attenuate muscle loss or recovery of strength or function 6-months post-ICU, but this requires exploration in a larger trial.Lee-anne S. Chapple, Matthew J. Summers, Luke M.Weinel, Kylie Lange, Woo Han Yang, Adam M. Deane, Marianne J. Chapman, The TARGET Investigators for the Australia and New Zealand Intensive Care Society Clinical Trials Grou

Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies

Recently our group and others have identified DDX41 mutations both as germ line and acquired somatic mutations in families with multiple cases of late onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML), suggesting that DDX41 acts as a tumor suppressor. To determine whether novel DDX41 mutations could be identified in families with additional types of hematologic malignancies, our group screened two cohorts of families with a diverse range of hematologic malignancy subtypes. Among 289 families, we identified nine (3%) with DDX41 mutations. As previously observed, MDS and AML were the most common malignancies, often of the erythroblastic subtype, and 1 family displayed early-onset follicular lymphoma. Five novel mutations were identified, including missense mutations within important functional domains and start-loss and splicing mutations predicted to result in truncated proteins. We also show that most asymptomatic mutation carriers have normal blood counts until malignancy develops. This study expands both the mutation and phenotypic spectra observed in families with germ line DDX41 mutations. With an increasing number of both inherited and acquired mutations in this gene being identified, further study of how DDX41 disruption leads to hematologic malignancies is critical.Maya Lewinsohn ...Anna L. Brown ... Luke M. Weinel ... Andreas W. Schreiber ... Agnes Yong ... Graeme K. Suthers ... Nicola Poplawski ... Richard J. D’Andrea ... Ian D. Lewis ... Akiko Shimamura ... Christopher N. Hahn ... Hamish S. Scott ... et al