These studies were conducted to investigate the role of dermal exposure to perfluorooctanoic acid (PFOA), a known immunosuppressant, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. PFOA has had widespread use as a carpet and fabric protectant. BALB/c mice were exposed dermally, on the dorsal surface of each ear, to concentrations of PFOA ranging from 0.01 to 1.5% (applied dose 0.25-50 mg/kg) for 4 days. In hypersensitivity studies, mice were also ip injected with 7.5 microg OVA and 2 mg alum on days 1 and 10 and in some studies challenged with 250 microg OVA by pharyngeal aspiration on days 17 and 26. Following exposure to PFOA, an increase in liver weights and a decrease in thymus and spleen weights and cellularities were observed. Similar immunomodulatory trends were demonstrated in mice coadministered PFOA and OVA. Compared to the OVA alone-exposed animals, an increase in total IgE was demonstrated when mice were coexposed to OVA and concentrations of PFOA ranging from 0.75 to 1.5%, while the OVA-specific IgE response peaked with 0.75% PFOA coexposure (p < or = 0.05). OVA-specific airway hyperreactivity was increased in the 1.0% PFOA coexposed group (p < or = 0.05), with an increased pleiotropic cell response characterized by eosinophilia and mucin production, in animals coexposed to concentrations of PFOA up to 1.0%, as compared to the OVA alone-exposed animals. In a murine model, PFOA was demonstrated to be immunotoxic following dermal exposure, with an enhancement of the hypersensitivity response to OVA, suggesting that PFOA exposure may augment the IgE response to environmental allergens.

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Objectives:The decision tree underlying current practice guidelines for post polypectomy surveillance relies on risk stratification based on predictive attributes gleaned from adenomas removed on screening colonoscopy examination. Our primary aim was to estimate the magnitude of association between baseline adenoma attributes and the risk of adenoma recurrence and invasive colorectal adenocarcinoma (CRC). Our secondary aims were to estimate the adenoma detection rate (ADR) of surveillance compared with screening colonoscopies and describe time trends in preventive colonoscopy utilization.Methods:We used prospective analyses of retrospectively collected clinical data from electronic health records. A cohort of primary care patients eligible for colorectal cancer screening was assembled encompassing 110,452 subjects, of which 3,300 had adenomas removed on screening examination. Of those patients who had a follow-up surveillance colonoscopy (defined as a patient with a documented adenoma on prior colonoscopy) recorded during the study period, 537 had a recurrent adenoma.Results:Of those recurrent adenomas, 354 had a high-risk attributes. High-risk attributes were described at >3 adenomas, at least one adenoma >10 mm in size, high-grade dysplasia, or villous features. The risk of developing invasive CRC among post polypectomy patients was significantly higher if the baseline adenomas displayed any of the following attributes: more numerous than 3 (4.3-fold higher risk, 95% confidence interval (CI) low, high 1.4, 12.9), larger than 10 mm in size (5.2-fold higher risk, 95% CI low, high 1.8, 15.1), high-grade dysplasia (13.2-fold risk, 95% CI low, high 2.8, 62.1), or villous features (7.4-fold higher risk, 95% CI low, high 2.5, 21.5). These attributes combined added a net value of 22.8% to the probability of correctly predicting CRC. There was a threefold increase in surveillance utilization relative to screening from 2005 to 2011. The ADR of surveillance (34.1%) was 1.5-fold higher than that of screening (23.1%).Conclusions:These results emphasize the need to mitigate excessive risk by performing timely surveillance colonoscopies in patients with baseline adenomas displaying high-risk attributes as recommended in practice guidelines.

Background/Aims: Triple therapy [adding protease inhibitors to standard of care (SOC)] dramatically increases treatment response in selected patients with hepatitis C virus (HCV). Interleukin 28B (IL28Β) genotyping helps predict responsiveness in these patients; however, the economic implications of IL28Β genotyping in HCV genotype 2 or 3 infected patients are unknown. Short- and long-term costs and outcomes of SOC therapy were calculated and used to determine the cost-effectiveness thresholds for using triple therapy in HCV genotype 2 or 3 infected patients. Methods: Costs and outcomes were calculated by conducting cohort simulations on decision trees modeling SOC and triple therapy. Quality-adjusted life expectancies and long-term costs were predicted through Markov modeling. Results: For triple therapy to be cost-effective, sustained virologic response (SVR) rates must improve (depending on age) by 7.91-11.11 and 9.06-12.8% for HCV genotype 2 and 3 cohorts, respectively. When triple therapy is guided by 2 IL28Β variants, a 2.63-3.72% improvement in SVR is needed for cost-effectiveness, and when guided by only one variant, a 1.4-8.91% improvement is needed. Conclusions: Markov modeling revealed that modest increases in SVR rates from IL28Β-guided triple therapy can lead to both lower costs and better health outcomes than SOC therapy in the long run.

Making a tissue diagnosis of pancreatic adenocarcinoma is best accomplished by EUS and fine-needle aspiration (FNA) of the lesion. Typically, a dark, or “hypoechoic” mass will be seen, which presents an obvious target for FNA. For small lesions, computerized tomography (CT) may be negative, but the lesion is still almost always seen on EUS imaging. Rarely, a pancreatic mass will appear isoechoic on EUS imaging. We report three “invisible” pancreatic masses identified only by a cutoff in the pancreatic duct (PD) and/or common bile duct (CBD). No mass, isoechoic or otherwise, was seen. EUS-FNA was performed in the area of ductal narrowing, with a positive identification of adenocarcinoma in these cases.