BACKGROUND: Second-line treatment with chemotherapy and anti-epidermal growth factor receptor or anti-vascular endothelial growth factor antibodies improves outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in second-line mCRC remains unclear. In this randomized, phase II estimation trial, we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab or bevacizumab in patients with disease progression during oxaliplatin-based chemotherapy and bevacizumab.
METHODS: One hundred eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), and safety.
RESULTS: PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.68-1.50; P = .97). Median PFS was 7.7 months (95% CI, 5.7-11.8) in the panitumumab arm and 9.2 months (95% CI, 7.8-10.6) in the bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95% CI, 0.75-1.49; P = .75). Median OS was 18.0 months (95% CI, 13.5-21.7) in the panitumumab arm and 21.4 months (95% CI, 16.5-24.6) in the bevacizumab arm. ORR was 32% (95% CI, 23%-43%) in the panitumumab arm and 19% (95% CI, 11%-29%) in the bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia, dehydration, and hypotension were more frequent in the panitumumab arm. Neutropenia was more frequent in the bevacizumab-containing arm.
CONCLUSIONS: Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy similar in patients whose disease progressed during oxaliplatin-based chemotherapy with bevacizumab, with expected toxicities. The development of more accurate biomarkers might help caregivers and patients to better choose between therapies for individual patients.

Despite the enormous public health impact of Alzheimer\'s disease (AD), no disease-modifying treatment has yet been proven to be efficacious in humans. A rate-limiting step in the discovery of potential therapies for humans is the absence of efficient non-invasive methods of evaluating drugs in animal models of disease. Magnetic resonance spectroscopy (MRS) provides a non-invasive way to evaluate the animals at baseline, at the end of treatment, and serially to better understand treatment effects. In this study, MRS was assessed as potential outcome measure for detecting disease modification in a transgenic mouse model of AD. Passive immunization with two different antibodies, which have been previously shown to reduce plaque accumulation in transgenic AD mice, was used as intervention. Treatment effects were detected by MRS, and the most striking finding was attenuation of myo-inositol (mIns) increases in APP-PS1 mice with both treatments. Additionally, a dose-dependent effect was observed with one of the treatments for mIns. MRS appears to be a valid in vivo measure of anti-Aβ therapeutic efficacy in pre-clinical studies. Because it is noninvasive, and can detect treatment effects, use of MRS-based endpoints could substantially accelerate drug discovery.

BACKGROUND: When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice.
METHODS: Contrast ultrasound of BAT (Definity 2 μL/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve\'s plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mm intervals after stimulation with NE and used to assess BAT volume and mass.
RESULTS: BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound-derived BAT mass was correlated with BAT mass obtained at necropsy (R(2) = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet.
CONCLUSIONS: Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass.

BACKGROUND: Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in 1 or more organs. Gastrointestinal manifestations of systemic mastocytosis have been previously studied in small cohorts of patients, and no specific histologic description is available.
OBJECTIVE: We sought to assess the clinical and pathologic features of gastrointestinal manifestations in patients with mastocytosis.
METHODS: Medical history and gastrointestinal symptoms of patients with mastocytosis (n = 83) were compared with those of matched healthy subjects (n = 83) by means of patient questionnaire. Data were analyzed for epidemiologic, clinical, biological, and genetic factors associated with gastrointestinal symptoms for patients with mastocytosis. A comparative analysis of gastrointestinal histology from patients with mastocytosis (n = 23), control subjects with inflammatory bowel disease (n = 17), and healthy subjects (n = 19) was performed.
RESULTS: The following gastrointestinal symptoms occurred more frequently and were more severe in patients with mastocytosis than in healthy subjects: bloating (33% vs 7.2%, P < .0001), abdominal pain (27.3% vs 4.8%, P < .0001), nausea (23% vs 8.4%, P = .02), and diarrhea (33.85% vs 1.2%, P < .0001). Patients with mastocytosis had a significantly higher incidence of personal history of duodenal ulcer (P = .02). Wild-type (WT) c-Kit was associated with diarrhea (P = .03). Specific histologic lesions were present in patients with mastocytosis but were not correlated with clinical symptoms.
CONCLUSIONS: Gastrointestinal manifestations in patients with mastocytosis are highly prevalent and often severe. Clinical symptoms do not correspond to histologic findings, are nonspecific, and can simulate irritable bowel syndrome.