Imaging features of marginal ulcers on multidetector CT.

AIM: To assess the inter-reader agreement and frequency of various imaging findings of marginal ulcers on computed tomography (CT) in a series of patients with endoscopically or surgically confirmed marginal ulcer disease. MATERIALS AND METHODS: This was a institutional review board-approved retrospective analysis involving a single academic institution. Eighty patients with a gastro-enteric anastomosis with confirmed marginal ulcer on endoscopy or surgery and multidetector (MD)CT performed within a month reviewed by two fellowship-trained abdominal radiologists to assess for the presence or absence of predetermined imaging characteristics categorised under signs of inflammation, signs of penetration, signs of perforation, and signs of obstruction. Inter-rater reliability was assessed using the Cohen kappa test. RESULTS: Findings of perforation had moderate to substantial agreement, including the presence of extraluminal air, extraluminal fluid, and leakage of oral contrast medium (kappa 0.83 [0.61, 1.05], 0.57 [0.35, 0.79] and 0.75 [0.18, 1.31], respectively) although these were present relatively infrequently (23-26%, 30-43%, 3-4%, respectively). Additional imaging characteristics with moderate agreement were the presence of perienteric fat stranding, a dilated stomach proximal to the anastomosis, and penetration into adjacent organ (kappa 0.45 [0.23, 0.69], 0.47 [0.26, 0.69], and 0.47 [0.25, 0.69], respectively) which were variably present (80-88%, 11-16%, 5%, respectively). Wall thickening and contour abnormalities, although frequently present (61-90% and 60-80%, respectively) had only slight to fair agreement (kappa 0.09 [-0.14, 0.30] and 0.29 [0.07, 0.51]). CONCLUSION: Signs of perforation have high inter-reader agreement but occur relatively infrequently. Fat stranding, wall thickening, and contour abnormalities are much more common; however, only fat stranding had moderate agreement.

The relationship between pretreatment dietary composition and weight loss during a randomised trial of different diet approaches.

BACKGROUND: Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake. METHODS: Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet (n = 71) or orlistat medication therapy plus a low-fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition. RESULTS: Participant's mean age was 53 years, baseline body mass index was 39.3 kg m(-2) and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition. CONCLUSIONS: Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.

Recruitment and Retention for a Weight Loss Maintenance Trial Involving Weight Loss Prior to Randomization.

OBJECTIVE: A weight loss maintenance trial involving weight loss prior to randomization is challenging to implement due to the potential for dropout and insufficient weight loss. We examined rates and correlates of non-initiation, dropout, and insufficient weight loss during a weight loss maintenance trial. METHODS: The MAINTAIN trial involved a 16-week weight loss program followed by randomization among participants losing at least 4 kg. Psychosocial measures were administered during a screening visit. Weight was obtained at the first group session and 16 weeks later to determine eligibility for randomization. RESULTS: Of 573 patients who screened as eligible, 69 failed to initiate the weight loss program. In adjusted analyses, failure to initiate was associated with lower age, lack of a support person, and less encouragement for making dietary changes. Among participants who initiated, 200 dropped out, 82 lost insufficient weight, and 222 lost sufficient weight for randomization. Compared to losing sufficient weight, dropping out was associated with younger age and tobacco use, whereas losing insufficient weight was associated with non-White race and controlled motivation for physical activity. CONCLUSIONS: Studies should be conducted to evaluate strategies to maximize recruitment and retention of subgroups that are less likely to initiate and be retained in weight loss maintenance trials.

The MDM2 small-molecule inhibitor RG7388 leads to potent tumor inhibition in p53 wild-type neuroblastoma.

Neuroblastoma is an aggressive pediatric malignancy which is >98% p53 wild-type at diagnosis. As a primary repressor of p53 activity and part of a p53-activated negative feedback loop, targeting of mouse double minute 2 homolog (MDM2) is an attractive therapeutic approach to reactivation of p53. Since development of the first selective MDM2 inhibitor, Nutlin-3a, newer compounds have been developed for increased potency and improved bioavailability. Herein, we sought to determine the efficacy and specificity of a second-generation MDM2 inhibitor, RG7388, in neuroblastoma cell lines and xenografts and examine its effect on the p53-independent pathway of hypoxia-inducible factor-1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF). Cell viability and apoptosis studies were performed on the neuroblastoma cell lines, NGP, SH-SY5Y, LAN-5, LAN-5 si-p53 (p53 silenced), and SK-N-AS (p53 null). RG7388 potently decreased cell proliferation and activated p53-dependent apoptosis. Tumor-bearing mice treated with RG7388 demonstrated significant tumor inhibition by 59% in NGP (P = 0.003), 67% in SH-SY5Y (P = 0.006), and 75% in LAN-5 (P = 0.0019) p53 wild-type xenograft tumors, but no inhibitory effect on LAN-5 si-p53 or SK-N-AS p53-silenced/null xenograft tumors. Moreover, RG7388 was found to inhibit the p53-independent pathway of HIF-1α/VEGF with decreased gene expression and alteration of angiogenesis. Our study supports the further evaluation of RG7388 as a novel treatment option in p53 wild-type neuroblastoma at diagnosis and relapse.

Effects of a brief mindfulness intervention on negative affect and urge to drink among college student drinkers.

Several theories have proposed that negative affect (NA) plays a large role in the maintenance of substance use behaviors - a phenomenon supported in laboratory-based and clinical studies. It has been demonstrated that mindfulness meditation can improve the regulation of NA, suggesting that mindfulness may be very beneficial in treating problematic substance use behavior. The current study tested whether a brief mindfulness meditation would lower levels of NA, increase willingness to experience NA, lower urges to drink, and increase time to next alcoholic drink in a sample of at-risk college student drinkers (N = 207). Participants were randomized to one of three brief interventions (mindfulness, relaxation, or control) followed by an affect manipulation (negative or neutral stimuli). Affect and urge were measured prior to intervention (Time 1 [T1]), after intervention but prior to affect manipulation (Time 2 [T2]), and immediately after the affect manipulation (Time 3 [T3]). Levels of mindfulness and relaxation were assessed from T1-T3. The additional measures of willingness to continue watching NA images and time to next alcoholic drink were examined at T3. Results indicated that the mindfulness intervention increased state mindfulness and relaxation, and decreased NA immediately following the mindfulness intervention. However, the mindfulness intervention did not influence responses to NA induction on any of the outcome variables at T3. One potential explanation is that the mindfulness intervention was not robust enough to maintain the initial gains made immediately following the intervention.

Idiopathic long QT syndrome: association of ventricular tachycardia with alternating left and right bundle branch block.

A case of sporadic long QT syndrome with ventricular tachycardia characteristic of torsades de pointes is presented. The ECG revealed sinus rhythm with marked prolongation (less than 140%) of QT interval and alternating periods of left and right bundle branch block. The onset of ventricular tachycardia was associated with alternating left and right bundle branch block and the disappearance of bundle branch block coincided with the resolution of ventricular tachycardia. This observation suggests the possibility that heterogeneous repolarization of the bundle branch system contributed to ventricular tachycardia either alone or in combination with dispersion of refractoriness of the ventricular myocardium.