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Background & Aims Practice guidelines recommend a 1-time screening endoscopy for patients with gastroesophageal reflux disease (GERD) who are at high risk for Barrett’s esophagus or malignancy. However, little is known about the risk of cancer in patients with negative findings from screening endoscopies. Methods We conducted a retrospective cohort study using data from 121 Veterans Health Administration facilities nationwide to determine the incidence rate of esophageal adenocarcinoma (EA) separately, as well as any upper gastrointestinal cancers, in patients with an initial negative screening endoscopy (esophagogastroduodenoscopy [EGD]). We included veteran patients with GERD diagnosed between 2004 and 2009 who had a negative screening EGD within 1 year of diagnosis. We estimated the incidence rate of EA, and any upper gastrointestinal cancer, in patients with GERD who had a negative screening EGD. We examined differences in demographic, clinical, and facility factors among patients with and without cancer. Results We identified 68,610 patients with GERD and a negative screening EGD (mean age, 55.5 y; 90% men; 67.5% white). During a mean follow-up period of 3.2 years, 10 patients developed EA and 29 patients developed any upper gastrointestinal malignancies, including EA. The incidence of subsequent EA in this group was 4.6/100,000 patient-years of follow-up evaluation, whereas the incidence of any upper gastrointestinal cancers was 13.2/100,000 patient-years of follow-up evaluation. Patients with a subsequent cancer were significantly older and had higher comorbidity scores than patients without cancer. Other clinical and facility factors did not differ significantly between these 2 groups. Conclusions The risk of cancer is low, over a mean 3-year period, for patients with GERD who had a negative screening endoscopy. These findings justify recommendations for a 1-time screening endoscopy for patients with GERD. [ABSTRACT FROM AUTHOR]

Background and Aims: It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known. Methods: Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC. Results: The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC ( p = 0.07), while there was a significant increase in ECC across the 4-year time periods ( p < 0.001). Klatskin tumors comprised 6.7 % of CCs with approximately 90 and 45 % misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors. Conclusions: The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs. [ABSTRACT FROM AUTHOR]

Background: Hispanics are the largest and fastest growing ethnic group in the United States (US). Aims: We evaluated the incidence and survival of colorectal cancer (CRC) among this population. Methods: Data from the surveillance, epidemiology, and end results program were used to calculate CRC age-adjusted and age-specific incidence rates in Hispanics during 1993-2007. Temporal trends in CRC incidence were examined using annual percent change (APC) and Poisson regression. The 1- and 5-year survival rates were calculated. Results: The annual age-adjusted incidence rates for CRC in Hispanics of all ages declined from 47.4 per 100,000 in 1993-1997 to 43.8 per 100,000 in 2003-2007, with an APC during 1993-2007 equal to −0.8/year. However, there was a 45 % increase in CRC incidence among Hispanic men and women aged 20-49 years that affected both the right and left colon. The proportions of CRC cases with regional (+37 %) and distant (+18 %) spread increased, now constituting 72 % of cases diagnosed at that age. The Poisson model confirmed the increasing CRC incidence in Hispanics aged 20-49 years during 1993-2007 while adjusting for sex and geographic region. The 1-year survival improved in younger Hispanics from approximately 86 % in 1993-1997 to 91 % in 2003-2007 with no significant improvement in 5-year survival. In Hispanics aged >50 years, no significant improvements in survival were observed. Conclusions: The incidence of CRC in young Hispanic men and women has increased in the US. Most are diagnosed with regional or distant disease. No significant improvement in long-term survival was observed in young Hispanics with CRC. [ABSTRACT FROM AUTHOR]

Background: Practice guidelines recommend surveillance endoscopy every 2 to 3 years among patients with Barrett''s esophagus (BE) to detect early neoplastic lesions. Although surveys report that >95% of gastroenterologists recommend or practice BE surveillance, the extent and patterns of surveillance in clinical practice are unknown. Objective: To identify the extent and determinants of endoscopic surveillance among BE patients. Design: Retrospective cohort study. Setting: A total of 121 Veterans Affairs facilities nationwide. Patients: Veteran patients with BE diagnosed from 2003 to 2009, with follow-up through September 30, 2010. Intervention: Not an interventional study. Main Outcome Measurements: The proportions of patients with BE who received any EGD after the index BE EGD date. In the subgroup of patients with at least 6 years of follow-up, we also calculated proportions for regular (EGD during both 3-year intervals), irregular (EGD in only 1 interval), and no surveillance. We examined differences in demographics and clinical and facility factors among these groups in unadjusted and adjusted analyses. Results: We identified 29,504 patients with BE; 97% were men, 83% white, and their mean age was 61.8 years. During a 3.8-year median follow-up period, 45.4% of patients with BE received at least one EGD. Among the subgroup of 4499 patients with BE who had at least 6 years of follow-up, 23.0% had regular surveillance, and 26.7% had irregular surveillance. There was considerable facility-level variation in percentages with surveillance EGD across the 112 facilities and by geographic region of these facilities. Demographic and clinical factors did not explain these variations. Patients with at least one EGD were significantly more likely to be white; to be aged <65 years, with a low level of comorbidity; to have GERD, obesity, dysphagia, or esophageal strictures; to have more outpatient visits; and to be seen in smaller hospitals (<87 beds) than those without any EGD. Limitations: There might be misclassification of BE and surveillance EGD. Lack of pathology data on dysplasia, which dictates surveillance intervals. Conclusion: Endoscopic surveillance for BE is considerably less commonly practiced in Veterans Affairs facilities than is self-reported by physicians. Although several clinical factors are associated with variations in surveillance, facility-level factors play a large role. The comparative effectiveness of the different practice-based surveillance patterns needs to be examined. [Copyright &y& Elsevier]

Background & Aims: Little information is available about what factors determine serum levels of alpha fetoprotein (AFP) (eg, demographic, virologic, or clinical features) among individuals who do not develop hepatocellular carcinoma (HCC). This information might improve AFP-based algorithms for HCC detection. Methods: We examined data from patients in the national Veterans'' Affairs Hepatitis C Virus (HCV) Clinical Case Registry who received at least 1 AFP test (258,275 AFP tests in 76,357 patients; 1.9% developed HCC). We constructed hierarchical multivariate models of AFP levels. Potential predictors of AFP values included patients'' sex, race, cirrhosis status, Model for End-Stage Liver Disease (MELD) score, HCV genotype, level of alanine aminotransferase (ALT) within 30 days before the AFP test, time to diagnosis of HCC, and time elapsed from the HCV index date. Results: Significant determinants for increased levels of AFP included presence of cirrhosis, higher MELD scores, and increased levels of ALT. AFP levels were also affected by the interaction between ALT levels and the presence and time to development of HCC. Among patients who did not have HCC, the AFP level increased with the level of ALT; the AFP values in the presence of ALT 37–56 U/L, ALT 57–92 U/L, or ALT >92 U/L were 16%, 35%, and 68% higher, respectively, than AFP values at ALT 0–36 U/L. However, patients who developed HCC within 30 days of receiving the AFP test had a lower rate of increase in AFP with each higher category of ALT level, with increases of 31%, 39%, and 37% for the same respective ALT categories. Conclusions: In patients with chronic HCV infection, AFP and ALT values correlate; however, among patients with HCC, levels of AFP increase disproportionately to or unaccompanied by increases in levels of ALT. The prognostic and diagnostic value of AFP levels might be increased by adjusting for ALT values. [Copyright &y& Elsevier]

Background & Aims: Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC. Methods: In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment. Results: The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively. Conclusions: Serum AFP level at the time of diagnosis with HCV-related HCC is an independent predictor of mortality. [Copyright &y& Elsevier]

The article details a study which investigated the relation between adiponectin, an adipocytokine with anti-inflammatory and antiatherogenic effects, and major depressive disorder (MDD) in premenopausal women. According to the study, adiponectin concentration has a relation with the severity of depression and the total duration of the disease. The study concludes that daily reduction of adiponectin production may result to high risk of diabetes mellitus in premenopausal women with MDD.

Objective: To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes.Research Design and Methods: Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal.Results: Individuals in the placebo group (n = 30) lost 56 +/- 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-alpha lost 29 +/- 54 and 48 +/- 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups.Conclusions: Ingested hrIFN-alpha was safe at the doses used. Patients in the 5,000-unit hrIFN-alpha treatment group maintained more beta-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-alpha. Further studies of low-dose ingested hrIFN-alpha in new-onset type 1 diabetes are needed to confirm this effect. [ABSTRACT FROM AUTHOR]

The application of standing surface acoustic wave (SSAW) tweezers based on backpropagation superposition to achieve precise behavior manipulation of microscale cells and even nanoscale bacteria has been widely studied and industrialized. However, the structure requires multiple transducer components or full channel resonance. It is very challenging to design a simple structure for nano-control by complex acoustic field. In this study, a reflector-interdigital transducer (R-IDT) acoustofluidic device based on unilateral coherence enhancement is proposed to achieve SSAW definition features of periodic particle capture positions. The SAW device based on a unilateral transducer can not only generate leaky-SAW in water-filled microchannel, but also have a contribution of spherical waves in the vibration area of the substrate-liquid interface due to the Huygens-Fresnel diffractive principle. Both of them form a robust time-averaged spatial periodicity in the pressure potential gradient, accurately predicting the lateral spacing of these positions through acoustic patterning methods. Furthermore, a reflector based on Bragg-reflection is used to suppress backward transmitted SAW and enhance forward conducted SAW beams. By using a finite element model, R-IDT structure's amplitude enhances 60.78% compared to single IDT structure. The particle manipulation range of the diffractive acoustic field greatly improves, verified by experimental polystyrene microspheres. Besides, biocompatibility is conformed through red blood cells and Bacillus subtilis. We investigate the overall shift of periodic pressure field that can still occur when the phase changes. This work provides a simpler and low-cost solution for the application of acoustic tweezer in biological cell culture and filtering. [ABSTRACT FROM AUTHOR]

With the existing pressure sensors, it is difficult to achieve the unification of wide pressure response range and high sensitivity. Furthermore, the preparation of pressure sensors with excellent performance for sleep health monitoring has become a research difficulty. In this paper, based on material and microstructure synergistic enhancement mechanism, a hybrid pressure sensor (HPS) integrating triboelectric pressure sensor (TPS) and piezoelectric pressure sensor (PPS) is proposed. For the TPS, a simple, low-cost, and structurally controllable microstructure preparation method is proposed in order to investigate the effect of carbon nano-onions (CNOs) and hierarchical composite microstructures on the electrical properties of CNOs@Ecoflex. The PPS is used to broaden the pressure response range and reduce the pressure detection limit of HPS. It has been experimentally demonstrated that the HPS has a high sensitivity of 2.46 V/104 Pa (50–600 kPa) and a wide response range of up to 1200 kPa. Moreover, the HPS has a low detection limit (10 kPa), a high stability (over 100,000 cycles), and a fast response time. The sleep monitoring system constructed based on HPS shows remarkable performance in breathing state recognition and sleeping posture supervisory control, which will exhibit enormous potential in areas such as sleep health monitoring and potential disease prediction. [ABSTRACT FROM AUTHOR]

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States. However, few data are available on recent trends in the incidence and prevalence of NAFLD in the U.S. Methods We analyzed the national Veterans Administration databases from 2003 to 2011 and calculated the age-adjusted prevalence and incidence of NAFLD for the overall sample of patients and by demographic subgroups. We used a previously validated algorithm to define NAFLD, which was based on persistent increases in levels of liver enzymes in the absence of positive results from tests for hepatitis C or hepatitis B or evidence of excessive alcohol use. Results Of the 9,784,541 patients with at least 1 visit to the Veterans Administration between 2003 and 2011, 1,330,600 patients (13.6%) had NAFLD. The annual incidence rates of NAFLD remained stable (from 2.2% to 3.2%) during the study duration. The prevalence of NAFLD increased from 6.3% in 2003 (95% confidence interval, 6.26%–6.3%) to 17.6% in 2011 (95% confidence interval, 17.58%–17.65%), a 2.8-fold increase. The incidence and prevalence increased at significantly greater rates in patients younger than 45 years vs older patients. Conclusions In a U.S. population, the annual incidence of NAFLD ranges from 2% to 3%. The prevalence of NAFLD more than doubled from 2003 through 2011; it is likely to continue to increase because of a steady overall incidence coupled with a rising incidence in younger individuals. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. population. Methods We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. Results A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4–8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1–7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. Conclusions Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis. [ABSTRACT FROM AUTHOR]

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. Methods We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients’ full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients. Results NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%–12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%–68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%–80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%–3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors. Conclusions NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC. [ABSTRACT FROM AUTHOR]