Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators?

Cancer and Metastasis Reviews - Branched-chain amino acids (BCAA) are essential amino acids utilized in anabolic and catabolic metabolism. While extensively studied in obesity and diabetes, recent...     

The metabolism of flubendazole in human liver and cancer cell lines

Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut‐residing nematodes in humans. In addition, FLU is now considered a promising anti‐cancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using ultra high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. Precision‐cut human liver slices and 9 cell lines of different origin (breast, colon, oral cavity) were used as in vitro model systems. Our study showed that FLU with a reduced carbonyl group (FLUR) is the only FLU metabolite formed in the human liver. All human cancer cell lines were able to form FLUR. In addition, methylated FLUR was detected in breast cells MCF7 and intestinal SW480 cells. The accumulation of FLU and its reduction to FLUR markedly differed among cells. The extent of FLU reduction was in a good correlation with the detected expression level of carbonyl reductase 1. In most cases, FLU entered in a higher amount and was reduced to a lesser extent in proliferating (metastatic) cells than in differentiated (non‐cancerous, non‐metastatic) ones. These results support the promising potential of FLU in anti‐cancer therapy.     

2.2 Continuous quality improvement

Continuous quality improvement (CQI) can be envisaged as a circular process of goal-setting, followed by external and internal evaluations resulting in improvements that can serve as goals for a next cycle. The need for CQI is apparent, because of public accountability, maintaining European standards and the improvement of dental education. Many examples are known where recommendations from both external and internal evaluation are used for the improvement of dental education. Unfortunately, the implementation of the recommendations is inconsistent, rarely systematic and usually not transparent. This section agreed that it is essential to apply CQI in a structured, systematic and transparent way if we are to improve and maintain the quality of dental education. A model is proposed which includes three aspects: a) the process of CQI; b) the subjects to which CQI should be applied; and c) the management tools to govern CQI. It is stressed, that CQI is a process that can be applied in any dental school irrespective of curriculum or educational approach within the relevant context of the country or the region. The approach needs to recognize the complexity and the need to balance a quality improvement with accountability. A CQI system is also constrained in any organization by the attitudes and values of the staff. Inevitably there has to be a wide range in the application of CQI. Nevertheless, an agreed model on CQI might enhance convergence towards higher standards of dental education. The process of CQI can be supported by developments in information and communication technology (ICT): collection of data, identifying the steps in CQI, formats of reports, etc. The section was set, as one of its tasks, to advise on the development of a network based on a number of case studies on the application of CQI in dental education.     

Long-term seizure outcome after stereotactic amygdalohippocampectomy

Background

The aim of the study was to evaluate the long-term seizure outcome and complications after stereotactic radiofrequency amygdalohippocampectomy (SAHE) performed for mesial temporal lobe epilepsy (MTLE).

Methods

The article describes the cases of 61 patients who were treated at our institution during the period 2004–2010. Mean post-operative follow-up was 5.3 years.

Results

At the last postsurgical visit, 43 (70.5 %) patients were Engel Class I, six (9.8 %) Class II, nine (14.8 %) Class III and three (4.9 %) Class IV. The surgery was complicated by four intracranial haematomas. One of them caused acute hydrocephalus and was treated by shunting and resolved without sequelae. After SAHE, we performed open epilepsy surgery and re-thermo lesions in three and two patients, respectively (8.2 %). There were two cases of meningitis which required antibiotic treatment. In six patients psychiatric disorders developed and one of these committed suicide due to postoperative depression.

Conclusions

Our results provide preliminary evidence for good long-term seizure outcomes after SAHE. SAHE could be an alternative therapy for MTLE.     

Renal parenchymal thickness in children with solitary functioning kidney

Background

Reduced renal parenchymal thickness (PT) is a parameter used by clinicians to assess the degree of hydronephrosis. In patients with a congenital hydronephrotic solitary functioning kidney (SFK), PT is difficult to determine as there is no comparison with the contralateral kidney. The aim of this study was to obtain ultrasound measurements of PT in children with normal SFK and to compare these data with PT measurements in children with two functioning kidneys.

Methods

This was a prospective multicenter study carried out between 2006 and 2011 in which 236 children aged 11 days to 18.96 years with healthy SFK were examined. The SFK etiologies were unilateral renal agenesis or a nonfunctioning contralateral kidney, mostly due to multicystic dysplasia. In addition to determining other parameters, we measured PT in the middle third of the kidney by ultrasound. Correlations between PT and age, height and weight were assessed.

Results

Correlation analysis showed a positive correlation with renal PT for all parameters. The correlation coefficients for age, height and weight were 0.863, 0.873 and 0.874, respectively. In most age categories, the renal parenchyma was significantly thicker in the SFK than in two functioning kidneys.

Conclusions

Based on our results, we suggest that PT in the SFK is correlated with height, weight and age of the patient. Consequently, measurements of PT may be used for monitoring the development of the healthy SFK and may contribute to a more accurate assessment of the severity of SFK anomalies.     

Data Improvement Through Simplification: Implications for Low-Resource Settings

Background

The focus of many data collection efforts centers on creation of more granular data. The assumption is that more complex data are better able to predict outcomes. We hypothesized that data are often needlessly complex. We sought to demonstrate this concept by examination of the American Society of Anesthesiologists (ASA) scoring system.

Methods

First, we created every possible consecutive two, three and four category combinations of the current five category ASA score. This resulted in 14 combinations of simplified ASA. We compared the predictive ability of these simplified scores for postoperative outcomes for 2.3 million patients in the NSQIP database. Individual model performance was assessed by comparing receiver operator characteristic (ROC) curves for each model with the standard ASA.

Results

Two of our 4-category models and one of our 3-category models had ability to predict all outcomes equivalent to standard ASA. These results held for all outcomes and on all subgroups tested. The performance of the three best performing simplified ASA scores were also equivalent to the standard ASA score in the univariate analysis and when included in a multivariate model.

Conclusions

It is assumed that the most granular data and use of the largest number of variables for risk-adjusted predictions will increase accuracy. This complexity is often at the expense of utility. Using the single best predictor in surgical outcomes research, we have shown this is not the case. In this example, we demonstrate that one can simplify ASA into a 3-category variable without losing any ability to predict outcomes.