Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore

Background To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.Methods We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.Results RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.Conclusions Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.Subject terms: Breast cancer, Breast cancer, Chemotherapy     

The Bucket Test Improves Detection of Stroke in Patients With Acute Dizziness

BackgroundIt is challenging to detect posterior circulation strokes in patients presenting to the emergency department (ED) with acute dizziness. The current approach uses a combinatorial head-impulse, nystagmus, and test-of-skew method and is sensitive enough to differentiate central causes from peripheral ones. However, it is difficult to perform and underused. Further, magnetic resonance imaging (MRI) of the brain is not always available and can have low sensitivity for detecting posterior circulation strokes.ObjectivesWe evaluated the feasibility and utility of the bucket test (BT), which measures the difference between patient's subjective perception of the visual vertical and the true vertical, as a screening tool for stroke in patients presenting to the ED with acute dizziness.MethodsIn this work, we prospectively enrolled 81 patients that presented to our academic medical center ED with dizziness as their chief complaint. The BT was performed 3 times for every patient.ResultsSeventy-one patients met the study criteria and were included in the analysis. Ten patients were excluded because of a history of drug-seeking behavior. There were no reported difficulties performing the BT. Six patients (8%) were diagnosed with ischemic stroke on MRI and 1 additional patient was diagnosed with transient ischemic attack and found to have a stroke on subsequent MRI. All 7 patients with dizziness attributed to cerebrovascular etiology had an abnormal BT, resulting in a sensitivity of 100% (95% confidence interval [CI] 59–100%). The specificity of the BT was 38% (95% CI 24–52%). The positive predictive value of the BT for detecting stroke was 18% (95% CI 15–21%).ConclusionsThe BT is an easy, cheap, safe, and quick test that is feasible and sensitive to screen acutely dizzy patients for stroke in the ED.     

Lifestyle factors in somatic patients with and without potential alcohol problems

Background

In the present study, we investigated the overall lifestyles of patients with hazardous alcohol use and alcohol dependence who were admitted to the hospital and investigated unhealthy lifestyle factors and their clustering in inpatients.

Methods

Patients admitted to the gastrointestinal, neurologic or orthopedic departments at Odense University Hospital or to the emergency department at Aabenraa Hospital in the inclusion period, October 2013 to June 2016, completed a lifestyle questionnaire asking questions about their diet, alcohol consumption, exercise and smoking habits. Patients were divided into three groups depending on their score from the alcohol use disorder identification test, which was embedded in the lifestyle questionnaire, and odds ratios were calculated using logistic regression.

Results

Patients with alcohol dependence had statistically significantly higher odds of being smokers, having unhealthy diets and being physically inactive compared with patients without alcohol problems. Among patients with hazardous alcohol drinking, we found an increased occurrence of smokers and an inverse association between hazardous alcohol drinking and being physically inactive. Many of the patients had attempted to change their unhealthy lifestyles.

Conclusion

We found that alcohol problems are related to a clustering of other lifestyle factors and that many of the patients admitted to certain departments showed signs of various kinds of alcohol problems. Therefore, specific hospital departments could be opportune settings for preventive alcohol interventions.

     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte–neuron interactions

Huntington''s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.     

Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.