Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.     

A guide to upwardly mobile spermatozoa

Morphological comparison of sperm in raw ejaculates and swim-ups showed that the swim-up process does not simply increase the proportion of 'normal' sperm. Rather, sperm of specific morphologies have characteristic grades of upward motility.     

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Management of hip dislocations in children with arthrogryposis

From a review of 131 children with arthrogryposis, we studied 18 patients with hip dislocations. Fourteen patients (10 unilateral, four bilateral) were treated by open reduction. Mean age at surgery was 9.7 months, and follow-up ranged from 9 to 245 months. Range of motion of patients treated by open reduction following the medial approach was greater than in those treated by anterolateral incision and greater than in bilateral cases treated by closed reduction. Acetabular development was satisfactory following the medial approach and there were no re-dislocations, but one hip developed avascular necrosis.     

Investigation and treatment of female urinary incontinence

There are four main types of urinary incontinence in the female namely stress incontinence, urge incontinence, overflow incontinence due to retention of urine and total incontinence. It is important to differentiate them to institute proper treatment. It is the aim of this paper to present a simple clinical evaluation of an incontinent woman. The different methods of surgical correction of stress incontinence are discussed. The latest trend is the paraurethral suspension of the bladder neck. 39 cases of Grade II stress incontinence were treated by paraurethral suspension of the bladder neck at "A" Unit, Kandang Kerbau Hospital and Dept. of Urology, SGH. 33 cases were cured. 4 improved with occasional stress incontinence, frequency and urgency. Of these, 3 were cured with imipramine. One failed because of a fixed, "lead pipe" rigid urethra from previous multiple operations to the bladder neck.