18F-Fluorodeoxyglucose Positron-Emission Tomography (PET) Can Be Used to Assess Inflammation Non-invasively in Crohn’s Disease

Background

Differential therapy requires repeated diagnostic assessment for mapping and monitoring of disease activity in Crohn’s disease (CD).

Purpose

The purpose of this prospective study was to evaluate the accuracy of ¹⁸F-fluorodexyglucose positron-emission tomography (FDG-PET) for non-invasive assessment of disease activity in CD.

Methods

Forty-three patients with CD underwent ileocolonoscopy and hydromagnetic resonance imaging (hydro-MRI) as reference standards. In addition, FDG-PET was performed and correlated with clinical data, hydro-MRI, and endoscopy findings. Diagnostic accuracy was determined for all methods.

Results

Two-hundred and forty-one bowel segments could be analyzed by all methods. Of 80 endoscopically inflamed segments in CD, FDG-PET detected 72 and hydro-MRI 53 segments. Overall sensitivity was 90 % (FDG-PET) versus 66 % (hydro-MRI), and specificity was 92.6 % versus 99 %. In the proximal ileum, hydro-MRI revealed inflammation in eight out of 49 patients and FDG-PET, also, detected all of these inflamed segments. Seventeen stenoses could be identified in 43 CD patients. With regard to assessment as inflammatory or fibrotic stenosis, there was good concordance between colonoscopy, hydro-MRI, and FDG-PET. In one case only, the nature of the stenosis was assessed differently. In contrast with leukocyte numbers and CDAI, there was significant correlation of FDG-PET activity with C-reactive protein and CDEIS levels (P = 0.019 and P = 0.007, respectively).

Conclusion

FDG-PET is able to detect mucosal inflammation in CD with high sensitivity and specificity and to enable proper assessment of inflammatory activity in stenoses. FDG-PET is, thus, a promising non-invasive technique for clinical management of CD.     

Dental erosion and salivary flow rate in cerebral palsy individuals with gastroesophageal reflux

J Oral Pathol Med (2012) 41 : 367–371 Background: A high prevalence of gastroesophageal reflux (GERD) has been observed in individuals with cerebral palsy (CP). One of the main risks for dental erosion is GERD. This study aimed to evaluate the presence of GERD, variables related to dental erosion and associated with GERD (diet consumption, gastrointestinal symptoms, bruxism), and salivary flow rate, in a group of 46 non‐institutionalized CP individuals aged from 3 to 13 years. Methods: Twenty CP individuals with gastroesophageal reflux (GERDG) and 26 without gastroesophageal reflux (CG) were examined according to dental erosion criteria, drinking habits, presence of bruxism, and salivary flow rate. A face‐to‐face detailed questionnaire with the consumption and frequency of acid drinks, gastrointestinal symptoms (regurgitation and heart burn), and the presence of bruxism were answered by the caregivers of both groups. Unstimulated whole saliva was collected under slight suction, and salivary flow rate (ml/min) was calculated. Results: The GERDG presented higher percentages of younger quadriplegics individuals compared to CG. The presence of regurgitation, heart burn, and tooth erosion (Grade 1) was significantly more prevalent in GERDG. It was observed difference in the salivary flow rate between the studied groups. On logistic multivariate regression analysis, the unique variable independently associated with the presence of GERD was dental erosion (P = 0.012, OR 86.64). Conclusion: The presence of GERD contributes significantly to dental erosion in the most compromised individuals with quadriplegics cerebral palsy individuals, increasing the risk of oral disease in this population.     

Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2

The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.     

Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project

Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.     

Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial

Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment. CONCLUSIONS: Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.     

Out of the group,out of control? The brain responds to social exclusion with changes in cognitive control

The effects of social exclusion are far-reaching, both on an emotional and behavioral level. The present study investigates whether social exclusion also directly influences basic cognitive functions, specifically the ability to exert cognitive control. Participants were either excluded or included while playing an online game. To test whether exclusion altered cognitive control, we measured the electrophysiological responses to a Go/No Go task. In this task participants had to withhold a response (No Go) on a small number of trials while the predominant tendency was to make an overt (Go) response. Compared to Go trials the event-related potential evoked by No Go trials elicited an increased N2, reflecting the detection of the response conflict, followed by an increased P3, reflecting the inhibition of the predominant response. The N2 effect was larger for participants who had experienced exclusion, while the P3 effect was smaller. This indicates that exclusion leads to an increased ability to detect response conflicts, while at the same time exclusion decreases the neural processes that underlie the inhibition of unwanted behavior.