The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for the unresectable and metastatic disease is dismal and unchanged for nearly three decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e., activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report, we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We show that Pax3:Fkhr expression increases during late preneoplasia but tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole-genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared with other pediatric cancers.
Objectives: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies.
Methods:We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. Results: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) −35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD −39.95; 95% CI −132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD −91.35; 95% CI −139.42 to −43.27; n = 2 studies). Conclusion: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.
Abstract:We investigated the clinical response of chronic heart failure patients with β 2 -adrenergic receptor Gln 27 → Glu polymorphism treated for 6 months with carvedilol, a α / β -antagonist with antioxidant properties. The 6-min. walk test, the left ventricular ejection fraction, heart rate, plasma norepinephrine and malondialdehyde, a stress oxidative marker, concentrations were evaluated at baseline and after treatment for 6 months with carvedilol in 33 stable chronic heart failure patients with the Gln 27 → Glu β 2 -adrenergic receptor polymorphism. Carvedilol significantly increased the left ventricular ejection fraction, while decreasing the heart rate and malondialdehyde plasma concentrations in chronic heart failure patients with the Glu 27 β 2 -adrenergic receptor allele. There were however, no significant changes in patients with the Gln 27 β 2 -adrenergic receptor variant.
Background: The development of balloon assisted enteroscopy (BAE) has revolutionized diagnostic and therapeutic modalities for small-bowel disorders. Although the role of emergent esophagogastroduodenoscopy and colonoscopy for upper and lower gastrointestinal bleeding is well defined, there is scarce data with regard to emergent BAE for gastrointestinal bleeding.
Study: We performed a retrospective cohort study including 110 hospitalized patients with obscure gastrointestinal bleeding who underwent single balloon enteroscopy (SBE) between January 2010 and August 2013. Patients were divided into two groups based on procedures performed emergently (within 24 hours) versus non-emergently (greater than 24 hours). Data on patient demographics, hemodynamic characteristics, type of obscure bleed, lesions identified, location of lesions, endoscopic intervention performed, need for further surgical or radiological intervention, diagnostic and therapeutic yield, and adverse events were compared between groups. Independent samples t test and Fisher’s exact test were used to assess the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and 95 % confidence intervals (CI), and for binary as odds ratio and 95 %CI.
Results: Although patients in the group where enteroscopy was performed within 24 hours had a significantly higher incidence of radiological intervention (10.0 % vs. 0.0 %, P = 0.019), the diagnostic and therapeutic yields between the two groups were not significantly different. Additionally, there were no statistically significant differences between the groups for overt and occult bleeding, transfusion requirements, type and location of lesions, endoscopic intervention performed, or adverse events. Hospital stay was shorter in the patients who had SBE within 24 hours of admission (6.2 vs. 11.3 days, P < 0.001).
Conclusions: Although the diagnostic and therapeutic yields of SBE were not significantly different between patients having the procedure within 24 hours and those having it later, the early SBE group required more interventional radiology procedures. While endoscopists may not necessarily have to perform emergent assessment within 24 hours in patients with obscure gastrointestinal bleeding (OGIB) for greater diagnostic or therapeutic yield, early intervention may allow for earlier stabilization and thus shorter hospital stays. Prospective studies further evaluating these findings are indicated.
Background and study aims Carbon dioxide (CO2) insufflation has
been suggested to be an ideal alternative to room air insufflation to reduce
trapped air within the bowel lumen after balloon assisted enteroscopy (BAE). We
performed a systematic review and meta-analysis to assess the safety and
efficacy of utilizing CO2 insufflation as compared to room air during
Patients and methods The primary outcome is mean change in visual analog
scale (VAS; 10 cm) at 1, 3, and 6 hours to assess pain. Secondary outcomes
include insertion depth (anterograde or retrograde), adverse events, total
enteroscopy rate, diagnostic yield, mean anesthetic dosage, and PaCO2
at procedure completion. We searched MEDLINE and the Cochrane Central Register
of Controlled Trials (CENTRAL) from inception until May 2015. Multiple
independent extractions were performed, the process was executed as per the
standards of the Cochrane collaboration.
Results Four randomized controlled trials (RCTs) were included in the
meta-analysis. VAS at 6 hours favored CO2 over room air (MD 0.13;
95 % CI 0.01, 0.25; p = 0.03). Anterograde insertion depth (cm) was improved in
the CO2 group (MD, 58.2; 95 % CI 17.17, 99.23; p = 0.005), with an
improvement in total enteroscopy rate in the CO2 group (RR 1.91; 95 %
CI 1.20, 3.06; p = 0.007). Mean dose of propofol (mg) favored CO2
compared to air (MD, – 70.53; 95 % CI – 115.07, – 25.98; P = 0.002).
There were no differences in adverse events in either group.
Conclusions Despite the ability of CO2 to improve insertion
depth and decrease amount of anesthesia required, further randomized control
trials are needed to determine the agent of choice for insufflation in balloon
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