• Novel missense germ line DDX41 mutations define an earlier age of onset of hematologic malignancies than loss-of-function alleles.• Carriers of DDX41 germ line mutations usually have normal blood counts until a myeloid or lymphoid malignancy develops.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.
Muscle wasting in the intensive care unit (ICU) is common and may impair functional recovery. Ultrasonography (US) presents a modern solution to quantify skeletal muscle size and monitor muscle wasting. However, no standardised methodology for the conduct of ultrasound-derived quadriceps muscle layer thickness or cross-sectional area in this population exists. The aim of this study was to compare methodologies reported for the measurement of quadriceps muscle layer thickness (MLT) and cross-sectional area (CSA) using US in critically ill patients. Databases PubMed, Ovid, Embase, and CINAHL were searched for original research publications that reported US-derived quadriceps MLT and/or CSA conducted in critically ill adult patients. Data were extracted from eligible studies on parameters relating to US measurement including anatomical location, patient positioning, operator technique and image analysis. It was identified that there was a clear lack of reported detail and substantial differences in the reported methodology used for all parameters. A standardised protocol and minimum reporting standards for US-derived measurement of quadriceps muscle size in ICU is required to allow for consistent measurement techniques and hence interpretation of results.
Enteral calorie delivery in excess of requirements (overfeeding) is believed to cause adverse effects during critical illness, but the literature supporting this is limited. We aimed to quantify the reported frequency and clinical sequelae of calorie overfeeding with enterally-delivered nutrition in critically ill adult patients. A systematic search of MEDLINE, EMBASE, and CINAHL from conception to November 28, 2018 was conducted to identify clinical studies of nutrition interventions in enterally-fed critically ill adults that reported overfeeding in one or more study arms. Overfeeding was defined as calorie delivery >2000 kcal per day, >25 kcal/kg per day, or ≥110% of calorie prescription. Data were extracted on methodology, demographics, prescribed and delivered nutrition, clinical variables and pre-defined outcomes. Cochrane "Risk of Bias" tool was used to assess the quality of RCTs. Eighteen studies were included; of which 10 were randomized (n=4386 patients) and 8 were non-randomized (n=223). Only 4 studies reported a separation in calorie delivery between treatment groups whereby one arm met the definition of overfeeding, for which no between-group differences in mortality, infectious complications or ventilatory support were reported. Overfeeding was associated with increased insulin administration (median 3 [IQR: 0-41.8] vs 0 [0-30.6] units/day) and upper gastrointestinal intolerance in one large RCT, and duration of antimicrobial therapy in a small RCT.There is limited high quality data to determine the impact of calorie overfeeding of critically ill patients by the enteral route; however, based on available evidence, does not appear to increase mortality or affect other important clinical outcomes.
Historically, randomized controlled trials (RCTs) in critical care have used mortality as the primary outcome, yet most show no effect on this outcome. Therefore, there has been a shift in the literature to focus on alternative outcomes. This review aimed to describe primary outcomes selected in RCTs of nutrition interventions in critical illness. Systematic search of the literature identified RCTs of nutrition interventions in critically ill adults published between January 2007 and December 2018. Primary outcomes were documented and categorized as mortality, morbidity, health service/cost-effectiveness, or nutrition outcome. The direction of effect of the intervention on the primary outcome (positive, neutral, or negative) was extracted. Of 1163 citations identified and assessed for eligibility, 125 articles were included. However, 52 articles (42%) did not provide a sample-size calculation, leaving 73 articles (58%) for data extraction. The primary outcomes reported were morbidity (n = 24, 32.9%); health service/cost-effectiveness (n = 21, 28.8%); nutrition outcomes (n = 16, 21.9%); mortality (n = 11, 15.1%); and other (n = 1, 1.4%). No RCTs with mortality as the primary outcome reported a difference between intervention and control. Trials that included other primary outcomes frequently reported a difference (n = 27 of 62; 43.5%). Morbidity was the most frequently reported outcome category in RCTs that evaluated a nutrition intervention in critically ill adults, with mortality least frequent. Power calculations were only reported in 58% of included studies. Trials were more likely to show a significant result when an outcome other than mortality was the primary outcome. (Nutr
Background: Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients. Methods: Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixedeffects models. Data presented are mean ± SE. Results: Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC 120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC 120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC 120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula. Conclusion: In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.