Malnutrition is associated with poor clinical outcomes among hospitalized patients. However, studies linking malnutrition with poor clinical outcomes in the intensive care unit (ICU) often have ...conflicting findings due in part to the inappropriate diagnosis of malnutrition. We primarily aimed to determine whether malnutrition diagnosed by validated nutrition assessment tools such as the Subjective Global Assessment (SGA) or Mini Nutritional Assessment (MNA) is independently associated with poorer clinical outcomes in the ICU and if the use of nutrition screening tools demonstrate a similar association. PubMed, CINAHL, Scopus, and Cochrane Library were systematically searched for eligible studies. Search terms included were synonyms of malnutrition, nutritional status, screening, assessment, and intensive care unit. Eligible studies were case-control or cohort studies that recruited adults in the ICU; conducted the SGA, MNA, or used nutrition screening tools before or within 48 hours of ICU admission; and reported the prevalence of malnutrition and relevant clinical outcomes including mortality, length of stay (LOS), and incidence of infection (IOI). Twenty of 1168 studies were eligible. The prevalence of malnutrition ranged from 38% to 78%. Malnutrition diagnosed by nutrition assessments was independently associated with increased ICU LOS, ICU readmission, IOI, and the risk of hospital mortality. The SGA clearly had better predictive validity than the MNA. The association between malnutrition risk determined by nutrition screening was less consistent. Malnutrition is independently associated with poorer clinical outcomes in the ICU. Compared with nutrition assessment tools, the predictive validity of nutrition screening tools were less consistent.
Background
Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there ...are limited studies on whether current screening techniques detect this pathology.
Aims
To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP.
Methods
A prospective study offered FIT and a blood test (Colvera for methylated
BCAT1
and
IKZF1
) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 μg hemoglobin (Hb)/g feces.
Results
One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated
BCAT1/IKZF1
. The sensitivity of FIT (20 μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%,
p
< 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 μg Hb/g feces (20.4%,
p
> 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT.
Conclusions
Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.
During the Millennium Development Goal (MDG) era, many countries in Africa achieved marked reductions in under-5 and neonatal mortality. Yet the pace of progress toward these goals substantially ...varied at the national level, demonstrating an essential need for tracking even more local trends in child mortality. With the adoption of the Sustainable Development Goals (SDGs) in 2015, which established ambitious targets for improving child survival by 2030, optimal intervention planning and targeting will require understanding of trends and rates of progress at a higher spatial resolution. In this study, we aimed to generate high-resolution estimates of under-5 and neonatal all-cause mortality across 46 countries in Africa.
We assembled 235 geographically resolved household survey and census data sources on child deaths to produce estimates of under-5 and neonatal mortality at a resolution of 5 × 5 km grid cells across 46 African countries for 2000, 2005, 2010, and 2015. We used a Bayesian geostatistical analytical framework to generate these estimates, and implemented predictive validity tests. In addition to reporting 5 × 5 km estimates, we also aggregated results obtained from these estimates into three different levels—national, and subnational administrative levels 1 and 2—to provide the full range of geospatial resolution that local, national, and global decision makers might require.
Amid improving child survival in Africa, there was substantial heterogeneity in absolute levels of under-5 and neonatal mortality in 2015, as well as the annualised rates of decline achieved from 2000 to 2015. Subnational areas in countries such as Botswana, Rwanda, and Ethiopia recorded some of the largest decreases in child mortality rates since 2000, positioning them well to achieve SDG targets by 2030 or earlier. Yet these places were the exception for Africa, since many areas, particularly in central and western Africa, must reduce under-5 mortality rates by at least 8·8% per year, between 2015 and 2030, to achieve the SDG 3.2 target for under-5 mortality by 2030.
In the absence of unprecedented political commitment, financial support, and medical advances, the viability of SDG 3.2 achievement in Africa is precarious at best. By producing under-5 and neonatal mortality rates at multiple levels of geospatial resolution over time, this study provides key information for decision makers to target interventions at populations in the greatest need. In an era when precision public health increasingly has the potential to transform the design, implementation, and impact of health programmes, our 5 × 5 km estimates of child mortality in Africa provide a baseline against which local, national, and global stakeholders can map the pathways for ending preventable child deaths by 2030.
Bill & Melinda Gates Foundation.
During the initial phase of critical illness, the association between the dose of nutrition support and mortality risk may vary among patients in the intensive care unit (ICU) because the prevalence ...of malnutrition varies widely (28 to 78%), and not all ICU patients are severely ill. Therefore, we hypothesized that a prognostic model that integrates nutritional status and disease severity could accurately predict mortality risk and classify critically ill patients into low- and high-risk groups. Additionally, in critically ill patients placed on exclusive nutritional support (ENS), we hypothesized that their risk categories could modify the association between dose of nutrition support and mortality risk.
A prognostic model that predicts 28-day mortality was built from a prospective cohort study of 440 patients. The association between dose of nutrition support and mortality risk was evaluated in a subgroup of 252 mechanically ventilated patients via logistic regressions, stratified by low- and high-risk groups, and days of exclusive nutritional support (ENS) short-term (≤ 6 days) vs. longer-term (≥ 7 days). Only the first 6 days of ENS was evaluated for a fair comparison.
The prognostic model demonstrated good discrimination AUC 0.78 (95% CI 0.73-0.82), and a bias-corrected calibration curve suggested fair accuracy. In high-risk patients with short-term ENS (≤ 6 days), each 10% increase in goal energy and protein intake was associated with an increased adjusted odds (95% CI) of 28-day mortality 1.60 (1.19-2.15) and 1.47 (1.12-1.86), respectively. In contrast, each 10% increase in goal protein intake during the first 6 days of ENS in high-risk patients with longer-term ENS (≥ 7 days) was associated with a lower adjusted odds of 28-day mortality 0.75 (0.57-0.99). Despite the opposing associations, the mean predicted mortality risks and prevalence of malnutrition between short- and longer-term ENS patients were similar.
Combining baseline nutritional status and disease severity in a prognostic model could accurately predict 28-day mortality. However, the association between the dose of nutrition support during the first 6 days of ENS and 28-day mortality was independent of baseline disease severity and nutritional status.
Introduction: The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric ...emptying, glucose absorption, and glycemia in health.
Methods: Ten healthy fasted subjects (eight males, two females; 48 ± 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide ex(9-39)NH2 (300 pmol/kg · min iv), or placebo, between −30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal (∼2600 kJ) containing 3 g 3-ortho-methyl-d-glucose (3-OMG) and labeled with 20 MBq 99mTechnetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured.
Results: Ex(9-39)NH2 accelerated gastric emptying T50 ex(9-39)NH2, 68 ± 8 min, vs. placebo, 83 ± 7 min; P < 0.001 and increased the overall glycemic response to the meal area under the curve (0-180 min) ex(9-39)NH2, 1540 ± 106 mmol/liter · min, vs. placebo, 1388 ± 90 mmol/liter · min; P < 0.02. At 60 min, ex(9-39)NH2 increased the rise in glycemia ex(9-39)NH2, 9.9 ± 0.5 mmol/liter, vs. placebo, 8.4 ± 0.5 mmol/liter; P < 0.01, plasma 3-OMG ex(9-39)NH2, 0.25 ± 0.01 mmol/liter, vs. placebo, 0.21 ± 0.01 mmol/liter; P < 0.05, and plasma insulin ex(9-39)NH2, 82 ± 13 mU/liter, vs. placebo, 59 ± 9 mU/liter; P < 0.05 concentrations. There was a close within-subject correlation between glycemia and gastric emptying e.g. at 60 min, the increment in blood glucose and gastric emptying (T50); r = −0.89; P < 0.001.
Conclusion: GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.
Endogenous glucagon-like peptide-1 has a role in regulating gastric emptying in humans, which consequently impacts glucose absorption and influences postprandial glycemia.
The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic ...effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients.
A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively.
Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72). When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment.
When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients.
The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).
Percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA) are both widely available curative treatments for hepatocellular carcinoma. Despite significant ...advances, it remains unclear which modality results in better outcomes. This meta-analysis of randomized controlled trials (RCT) and observational studies was undertaken to compare the techniques in terms of effectiveness and safety.
Electronic reference databases (Medline, EMBASE and Cochrane Central) were searched between January 1980 and May 2014 for human studies comparing RFA and MWA. The primary outcome was the risk of local tumor progression (LTP). Secondary outcomes were complete ablation (CA), overall survival, and major adverse events (AE). The ORs were combined across studies using the random-effects model.
Ten studies (two prospective and eight retrospective) were included, and the overall LTP rate was 13.6% (176/1298). There was no difference in LTP rates between RFA and MWA OR (95% CI): 1.01(0.67-1.50), P = 0.9. The CA rate, 1- and 3-year overall survival and major AE were similar between the two modalities (P > 0.05 for all). In subgroup analysis, there was no difference in LTP rates according to study quality, but LTP rates were lower with MWA for treatment of larger tumors 1.88(1.10-3.23), P = 0.02. There was no significant publication bias or inter-study heterogeneity (I(2) < 50% and P > 0.1) observed in any of the measured outcomes.
Overall, both RFA and MWA are equally effective and safe, but MWA may be more effective compared to RFA in preventing LTP when treating larger tumors. Well-designed, larger, multicentre RCTs are required to confirm these findings.
Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with ...CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA).
Whole-slide images of The Cancer Genome Atlas Project (TCGA, N = 260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N = 199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC. Genomic instability was assessed by calculating the percentage of genome altered (PGA). Somatic copy number alterations (CNA) were determined using Fisher-Boschloo tests and logistic regression. Primary analysis were performed on TCGA (N = 260) as discovery and CPC-GENE (N = 199) as validation set.
CR/IDC growth was present in 80/260 (31%) TCGA and 76/199 (38%) CPC-GENE cases. Patients with CR/IDC and ≥ GS 7 had significantly higher PGA than men without this pattern in both TCGA (2.2 fold; p = 0.0003) and CPC-GENE (1.7 fold; p = 0.004) cohorts. CR/IDC growth was associated with deletions of 8p, 16q, 10q23, 13q22, 17p13, 21q22, and amplification of 8q24. CNAs comprised a total of 1299 gene deletions and 369 amplifications in the TCGA dataset, of which 474 and 328 events were independently validated, respectively. Several of the affected genes were known to be associated with aggressive prostate cancer such as loss of PTEN, CDH1, BCAR1 and gain of MYC. Point mutations in TP53, SPOP and FOXA1were also associated with CR/IDC, but occurred less frequently than CNAs.
CR/IDC growth is associated with increased genomic instability clustering to genetic regions involved in aggressive prostate cancer. Therefore, CR/IDC is a pathologic substrate for progressive molecular tumour derangement.
Although enteral nutrition is standard care for critically ill patients, nutrient absorption has not been quantified in this group and may be impaired due to intestinal dysmotility. The objectives of ...this study were to measure small intestinal glucose absorption and duodenocecal transit and determine their relationship with glycemia in the critically ill.
Prospective observational study of healthy and critically ill subjects.
Tertiary mixed medical-surgical adult intensive care unit.
Twenty-eight critically ill patients and 16 healthy subjects were studied. MATERIALS AND MAIN RESULTS: Liquid feed (100 kcal/100 mL), labeled with Tc-sulfur colloid and including 3 g of 3-O-methylglucose, was infused into the duodenum. Glucose absorption and duodenocecal transit were measured using the area under the 3-O-methylglucose concentration curve and scintigraphy, respectively. Data are median (range).
Glucose absorption was reduced in critical illness when compared to health (area under the concentration curve: 16 1-32 vs. 20 14-34 mmol/L·min; p = .03). Small intestinal transit times were comparable in patients and healthy subjects (192 9-240 vs. 168 6-240 min; p = .99) and were not related to glucose absorption. Despite higher fasting blood glucose concentrations (6.3 5.1-9.3 vs. 5.7 4.6-7.6 mmol/L; p < .05), the increment in blood glucose was sustained for longer in the critically ill (Δ glucose at t = 60; 1.9 -2.1-5.0 mmol/L vs. -0.2 -1.3-2.3 mmol/L; p < .01).
Critical illness is associated with reduced small intestinal glucose absorption, but despite this, the glycemic response to enteral nutrient is sustained for longer.
Abstract
Background
Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening; however, high ambient temperatures were found to reduce test accuracy. More recently, ...proprietary globin stabilizers were added to FIT sample buffers to prevent temperature-associated hemoglobin (Hb) degradation, but their effectiveness remains uncertain. We aimed to determine the impact of high temperature (>30°C) on OC-Sensor FIT Hb concentration with current FITs, characterize FIT temperatures during mail transit, and determine impact of ambient temperature on FIT Hb concentration using data from a CRC screening program.
Methods
FITs were analyzed for Hb concentration after in vitro incubation at different temperatures. Data loggers packaged alongside FITs measured temperatures during mail transit. Separately, screening program participants completed and mailed FITs to the laboratory for Hb analysis. Regression analyses compared the impact of environmental variables on FIT temperatures and separately on FIT sample Hb concentration.
Results
In vitro incubation at 30 to 35°C reduced FIT Hb concentration after >4 days. During mail transit, maximum FIT temperature averaged 6.4°C above maximum ambient temperature, but exposure to temperature above 30°C was for less than 24 hours. Screening program data showed no association between FIT Hb concentration and maximum ambient temperatures.
Conclusions
Although FIT samples are exposed to elevated temperatures during mail transit, this is brief and does not significantly reduce FIT Hb concentration. These data support continuation of CRC screening during warm weather with modern FITs with a stabilizing agent when mail delivery is ≤4 days.
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