Microcephaly genes and risk of late-onset Alzheimer disease

Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P=0.01; odds ratio=3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small.     

Glycaemic variability: The under-recognized therapeutic target in type 1 diabetes care

Type 1 diabetes mellitus (T1DM) remains one of the most challenging long-term conditions to manage. Despite robust evidence to demonstrate that near normoglycaemia minimizes, but does not completely eliminate, the risk of complications, its achievement has proved almost impossible in a real-world setting. HbA1c to date has been used as the gold standard marker of glucose control and has been shown to reflect directly the risk of diabetes complications. However, it has been recognized that HbA1c is a crude marker of glucose control. Continuous glucose monitoring (CGM) provides the ability to measure and observe inter- and intraday glycaemic variability (GV), a more meaningful measure of glycaemic control, more relevant to daily living for those with T1DM. This paper reviews the relationship between GV and hypoglycaemia, and micro- and macrovascular complications. It also explores the impact on GV of CGM, insulin pumps, closed-loop technologies, and newer insulins and adjunctive therapies. Looking to the future, there is an argument that GV should become a key determinant of therapeutic success. Further studies are required to investigate the pathological and psychological benefits of reducing GV.     

Adverse effects of preoperative steroid use on surgical outcomes

Background

Preoperative steroid use has been associated with increased postoperative complications. We sought to establish these risks using data from the National Surgical Quality Improvement Program (NSQIP).

Methods

NSQIP public use files from 2005 to 2008 were analyzed for preoperative steroid use and postoperative adverse events.

Results

Of 635,265 patients identified, 20,434 (3.2%) used steroids preoperatively. Superficial surgical site infections (SSI) increased from 2.9% to 5% using steroids (odds ratio, 1.724). Deep SSIs increased from .8% to 1.8% (odds ratio, 2.353). Organ/space SSIs and dehiscence increased 2 to 3-fold with steroid use (odds ratios, 2.469 and 3.338, respectively). Mortality increased almost 4-fold (1.6% to 6.0%; odds ratio, 3.920). All results were significant (P < .001).

Conclusions

Previous concerns related to surgical risks in patients on chronic steroid regimens appear valid. These results may assist in counceling patients regarding the increased risk of surgery. They may also help the surgeon plan and modify the procedure if possible.     

Evaluation of the ‘dose of the day’ for IMRT prostate cancer patients derived from portal dose measurements and cone-beam CT

Purpose

High geometrical and dosimetrical accuracies are required for radiotherapy treatments where IMRT is applied in combination with narrow treatment margins in order to minimize dose delivery to normal tissues. As an overall check, we implemented a method for reconstruction of the actually delivered 3D dose distribution to the patient during a treatment fraction, i.e., the ‘dose of the day’. In this article results on the clinical evaluation of this concept for a group of IMRT prostate cancer patients are presented.

Materials and methods

The actual IMRT fluence maps delivered to a patient were derived from measured EPID-images acquired during treatment using a previously described iterative method. In addition, the patient geometry was obtained from in-room acquired cone-beam CT images. For dose calculation, a mapping of the Hounsfield Units from the planning CT was applied. With the fluence maps and the modified cone-beam CT the ‘dose of the day’ was calculated. The method was validated using phantom measurements and evaluated clinically for 10 prostate cancer patients in 4 or 5 fractions.

Results

The phantom measurements showed that the delivered dose could be reconstructed within 3%/3 mm accuracy. For prostate cancer patients, the isocenter dose agreed within −0.4 ± 1.0% (1 SD) with the planned value, while for on average 98.1% of the pixels within the 50% isodose surface the actually delivered dose agreed within 3% or 3 mm with the planned dose. For most fractions, the dose coverage of the prostate volume was slightly deteriorated which was caused by small prostate rotations and small inaccuracies in fluence delivery. The dose that was delivered to the rectum remained within the constraints used during planning. However, for two patients a large degrading of the dose delivery was observed in two fractions. For one patient this was related to changes in rectum filling with respect to the planning CT and for the other to large intra-fraction motion during treatment delivery, resulting in mean underdosages of 16% in the prostate volume.

Conclusions

A method to accurately assess the ‘dose of the day’ was evaluated for prostate cancer patients treated with IMRT. To correct for observed dose deviations off-line dose-adaptive strategies will be developed.