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Journal Cover Journal of Town and City Management
   [11 followers]  Follow    
   Full-text available via subscription Subscription journal
     ISSN (Print) 1756-9538 - ISSN (Online) 1756-9591
     Published by Henry Stewart Publications Homepage  [18 journals]
  • The Consequences of Cirrhosis in America
    • PubDate: 2014-11-16
  • Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and
           Epithelial Barrier Disruption
    • Abstract: Background Gut inflammation is prevalent in chronic kidney disease (CKD) and likely contributes to systemic inflammation via disruption of the epithelial tight junction with subsequent endotoxin and bacterial translocation. Aims To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator. Methods CKD was induced via 5/6 nephrectomy in Sprague–Dawley rats, and dh404 (2 mg/kg/day) was used to study the effects of systemic Nrf2 activation. The experimental groups included sham, CKD and CKD+ dh404 rats. Blood and colon tissues were analyzed after a 10-week study period. Results Colon from CKD rats showed histological evidence of colitis, depletion of epithelial tight junction proteins, significant reduction of Nrf2 and its measured target gene products (NQO1, catalase, and CuZn SOD), activation of NFkB, and upregulation of pro-inflammatory molecules (COX-2, MCP-1, iNOS, and gp91phox). Treatment with dh404 attenuated colonic inflammation, restored Nrf2 activity and levels of NQO1, catalase and CuZn SOD, decreased NFkB and lowered expression of COX-2, MCP-1, iNOS, and gp91phox. This was associated with restoration of colonic epithelial tight junction proteins (occludin and claudin-1). Conclusions CKD rats exhibited colitis, disruption of colonic epithelial tight junction, activation of inflammatory mediators, and impairment of Nrf2 pathway. Treatment with an Nrf2 activator restored Nrf2 activity, attenuated colonic inflammation, and restored epithelial tight junction proteins.
      PubDate: 2014-11-16
  • Trend of Improving Prognosis of Hepatocellular Carcinoma in Clinical
           Practice: An Italian In-Field Experience
    • Abstract: Background Recent data suggest that outcome of hepatocarcinoma is improving. Aims In order to explore whether survival is also increasing in clinical practice, we compared two multicenter independent in-field cohorts of cirrhotics with newly diagnosed HCCs. Methods Cohort 1 (C1) consisted of 327 patients enrolled between January and December 1998, and cohort 2 (C2) included 826 patients enrolled between September 2008 and November 2012. Patients were stratified according to Child-Pugh score, MELD score, and HCC staged according to TNM, BCLC systems. Results At baseline, C2 patients were significantly older, with more frequent comorbidities and better liver function. In C2, HCC was more frequently detected under regular ultrasound surveillance (P < 0.001), BCLC early stages were more frequent, and rates of smaller and uni/paucinodular tumors were significantly higher. Treatment of any type was more frequently offered to C2 patients (P < 0.001). Proportion of patients treated by TACE increased, and radiofrequency ablation was the most used ablative treatment. Survival rate was significantly higher in C2 being C1 and C2 survival at 1–3 years 72–25 and 75–44 %, respectively. Child-Pugh score A, BCLC stage A, single nodule, size ≤3 cm, belonging to cohort C2 and treatment per se independently predicted survival. Conclusions This in-field study showed a trend on improved HCC outcomes over time, which seems to be mainly due to a better presentation thanks to the wider application of surveillance and increased propensity to treat patients. These encouraging data should support further efforts to implement such approach to HCC in everyday clinical practice.
      PubDate: 2014-11-16
  • Management and Disease Outcome of Type I Gastric Neuroendocrine Tumors:
           The Mount Sinai Experience
    • Abstract: Background and Aim The incidence of gastric neuroendocrine tumors (NETs) has increased tenfold since the 1970s. Our aim was to describe the clinicopathologic profile, management, and outcomes of type I gastric NETs at The Mount Sinai Hospital. Methods From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56 patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to 2012. We generated a comprehensive dataset encompassing demographic, clinical, endoscopic, and pathologic factors. Survival information was determined from medical records and the Social Security Death Index. Tumor–node–metastasis staging was conducted, and tumors were graded based on mitotic counts and Ki67 index. Results Median NET size was 3.0 mm; 55.8 % displayed multifocal disease. Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %, respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade. Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 % underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical resection. 5- and 10-year disease-specific survival was 100 %. Conclusions Most patients received annual endoscopic surveillance, with a minority undergoing surgical resection, though outcomes remained excellent independent of therapeutic approach. We identified a very low but real rate of loco-regional spread, despite the generally indolent behavior of type I gastric NETs. Several patients demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of regular endoscopic management not only for gastric NETs, but also for dysplasia and adenocarcinoma.
      PubDate: 2014-11-16
  • Fat and Fiber: How the Controlled Attenuation Parameter Complements
           Noninvasive Assessment of Liver Fibrosis
    • PubDate: 2014-11-16
  • Clinical Utility of Wireless Motility Capsule in Patients with Suspected
           Multiregional Gastrointestinal Dysmotility
    • Abstract: Background Patients with gastrointestinal (GI) dysmotility often experience overlapping upper and lower GI symptoms suggestive of multiregional involvement. Wireless motility capsule (WMC) provides a full GI tract transit profile and may be able to detect and diagnose multiregional dysmotility. Aim To determine the clinical utility and diagnostic yield of WMC in patients with upper and lower GI symptoms suggestive of multiregional GI dysmotility. Methods Retrospective chart review of all patients who had undergone WMC testing for suspected multiregional GI dysmotility from January 2009 to December 2012 at our institution was performed. Information regarding demographics, symptoms, medication use, prior diagnostic studies, and results of WMC testing was collected. Results A total of 161 patients were included in the analysis. Mean age was 43 ± 15 years, and 83 % were female. WMC was abnormal in 109 (67.7 %) subjects. Of these, 17 (15.6 %) patients had isolated delayed gastric emptying, 13 (11.9 %) patients had isolated delayed small bowel transit, and 25 (22.9 %) patients had isolated delayed large bowel transit. Multiregional dysmotility was diagnosed in 54 (49.5 %) patients. There was no significant difference in past medical or past surgical history between patients with isolated regional versus multiregional involvement. The presence or absence of various patient-reported symptoms by history did not predict an abnormal WMC study. Conclusions Patients’ symptoms are poor predictors of GI dysmotility and its anatomical extent. WMC can be a useful diagnostic test in these patients as it provides a comprehensive evaluation of the motility profile of the entire GI tract and provides objective evidence of multiregional involvement.
      PubDate: 2014-11-16
  • Good Vibrations: Successful Endoscopic Electrohydraulic Lithotripsy for
           Bouveret’s Syndrome
    • PubDate: 2014-11-09
  • Hepatic Decompensation Likely Attributable to Simeprevir in Patients with
           Advanced Cirrhosis
    • Abstract: Background Hyperbilirubinemia is a common side effect of protease inhibitors used to treat chronic hepatitis C (HCV), and most patients do not experience without clinically overt hepatotoxicity. The safety of second-wave protease inhibitors, including simeprevir, has not been well studied in patients with advanced cirrhosis. Materials & Methods We report two cases of suspected drug-induced liver injury leading to hepatic decompensation in patients with advanced HCV cirrhosis treated with the combination of simeprevir and sofosbuvir on a compassionate basis. Both patients developed marked hyperbilirubinemia out of proportion to their aminotransferases, despite clearance of hepatitis C RNA. RUCAM scoring was probable and possible, respectively. While other factors may have contributed to the liver injury, including infection and concurrent administration of other medications, we believe that the potentially deleterious hepatic effects of simeprevir on transporters or other key functional components were the main reason for their decompensation. Conclusions Protease inhibitors should be used with caution, if at all, in patients with cirrhosis, especially in those with the most advanced disease. We await newer, safer, direct-acting antiviral therapies for such patients, especially those on our transplant list.
      PubDate: 2014-11-06
  • Reply “Endoscopic Therapy with 2-Octyl-Cyanoacrylate for the
           Treatment of Gastric Varices”: Optimizing the Cyanoacrylate
           Injection in the Treatment of Gastric Varices
    • PubDate: 2014-11-05
  • Utility of Evaluating HCV in an Uninsured Population
    • Abstract: Objectives Although effective HCV treatment is available, it can be difficult to access for uninsured, urban patients. Our aim was to assess the utility of evaluation and outcomes in the uninsured with HCV when access to health care and treatment with triple therapy is provided. Methods We performed a retrospective review of consecutive patients referred for HCV from 2011 to June 2013 to an indigent HCV clinic. The primary outcomes were assessment of disease severity by noninvasive means and initiation of therapy. Results We identified 350 patients: mean age 50.6, 84 % with no insurance, 62 % men, 58 % black, 91 % HCV treatment naïve. Of these, 148 underwent liver biopsy and 68 % had F0–F1 and 10 % had F3–F4 fibrosis. FIB-4 and APRI were highly correlated (r = 0.9; p < .0001) and correctly classified patients by fibrosis strata (F0–F1, F2, and F3–F4; p = .0004). When combined, a FIB-4 ≤1.5 and APRI ≤0.5 correctly classified the absence of advanced disease in 97 % (p < .0001). Of those evaluated, 39 (11 %) went on to HCV treatment. Of those not in a clinical trial, 51 % completed treatment with SVR in 61 % with genotype 1 and 75 % in genotypenon-1. Of those not treated (n = 309), the most common reasons were mild disease (16 %), lost to follow-up (23 %), ongoing alcohol or substance abuse (24 %), and uncontrolled depression (10 %). Conclusion Noninvasive assessment can accurately exclude advanced fibrosis. Despite access to care, the utility of evaluating to initiate HCV treatment is low suggesting that eliminating the barrier to health care may not increase HCV treatment.
      PubDate: 2014-11-05
  • Roles of Toll-Like Receptor 4, IκB Kinase, and the Proteasome in the
           Intestinal Alterations Caused by Sepsis
    • Abstract: Background Lipopolysaccharide decreases intestinal contractility and induces the production of cytokines, which play an important role in the pathogenesis of sepsis. Aim The objective of the present study was to examine the role of Toll-like receptor 4, IκB kinase, and the proteasome in the intestinal alterations induced by lipopolysaccharide. Methods Sepsis was induced in rabbits by intravenous injection of lipopolysaccharide. Contractility studies of rabbit duodenum were performed in an organ bath. Expressions of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, IκB kinase-α, IκB kinase-β, IκB kinase-γ, and the proteasome mRNA were determined by RT-PCR on rabbit duodenum. Results Neomycin and polymyxin B (Toll-like receptor 4 inhibitors), IKK NBD peptide (IκB kinase complex inhibitor), and MG-132 (proteasome inhibitor) blocked partially the effects of lipopolysaccharide on the acetylcholine-, prostaglandin E2-, substance P-, and KCl-induced contractions in the longitudinal and circular smooth muscle of rabbit duodenum. Lipopolysaccharide increased the mRNA expression of interleukin-6 and interleukin-8 in duodenal tissue, and this effect was partly reversed by neomycin, polymyxin B, IKK NBD peptide, and MG-132. IκB kinase-α, IκB kinase-β, IκB kinase-γ, and the proteasome mRNA expressions was not affected by lipopolysaccharide treatment. Conclusions Toll-like receptor 4, the IκB kinase complex, and the proteasome could be therapeutic targets in the treatment of sepsis symptoms in the intestine.
      PubDate: 2014-11-05
  • Persisting Early Hypotension: Is This Why Necrosis Gets Infected in Acute
    • PubDate: 2014-11-05
  • Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term
           Outcomes of Patients with Hepatocellular Carcinoma
    • Abstract: Background Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC. Methods We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting. Results/Conclusion High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.
      PubDate: 2014-11-05
  • Acute Liver Failure: A Potential Complication of Antithyroid Medication
    • PubDate: 2014-11-04
  • Predictors of Poor Adherence of US Gastroenterologists with Colonoscopy
           Screening and Surveillance Guidelines
    • Abstract: Background The US Multi-Society Task Force on Colorectal Cancer published guidelines for colonoscopy screening and surveillance in 2008 and affirmed them in 2012. Characteristics associated with guideline adherence among US gastroenterologists have not been assessed. Aim Assess awareness and adherence of US gastroenterologists with national guidelines for colonoscopy screening and surveillance and predictors of adherence to guidelines. Methods A Web-based survey was administered to gastroenterologists in various practice settings across the USA. Results A total of 306 gastroenterologists completed the survey; 86 % reported awareness of the guidelines. Low-volume colonoscopists (<20/month) were less likely to be aware of the guidelines (OR 0.26, p = 0.03) compared to high-volume colonoscopists (>100/month). Those completing training before 1990 were less likely to report following guidelines (OR 0.37, p = 0.01). Adherence with guidelines was then assessed via clinical scenarios. Compared to physicians finishing training in 1991–2010, less adherence was seen in those finishing before 1990 (OR 0.75, p < 0.001) or currently in training (OR 0.72, p = 0.004). Compared to the Western USA, less adherence was seen in the Midwest (OR 0.69, p = 0.001), Northeast (OR 0.63, p < 0.001), and South (OR 0.59, p < 0.001). Lower adherence was seen among non-academic physicians (OR 0.72, p = 0.001) and low-volume colonoscopists (OR 0.52, p < 0.001). Conclusions There is poor adherence with colonoscopy screening and surveillance guidelines among US gastroenterologists. Poor adherence was associated with being in training or finishing training before 1990, practicing in the South, non-academic settings, and low colonoscopy volume. These findings can target interventions for quality improvement in colorectal cancer screening and surveillance.
      PubDate: 2014-11-04
  • Effects of Age at Disease Onset and at Treatment on Serology in
           Inflammatory Bowel Diseases
    • PubDate: 2014-11-04
  • Distal Duodenum Versus Duodenal Bulb: Intraepithelial Lymphocytes Have
           Something to Say in Celiac Disease Diagnosis
    • Abstract: Background and Aim After clinical screening and the serological test, many patients still require a duodenal biopsy for celiac disease diagnosis. Mild histological lesions, unspecific findings and patchiness are frequent outcomes of this mandatory diagnostic tool, thus complicating clinical decisions. Methods We analyzed the lymphoid components [number of total intraepithelial lymphocytes (IELs), TcR-γδ and CD3−IELs] of the duodenal epithelium by flow cytometry in samples obtained from bulb and distal duodenum during upper gastrointestinal endoscopies performed for diagnostic purposes. Results IEL counts and IEL subset distribution (IEL lymphogram) remain invariant along duodenal mucosa revealing a specific profile (immunophenotype) that characterizes either a healthy mucosa or a celiac mucosa. The celiac immunophenotype persists regardless of the biopsy’s anatomical location or the corresponding histological findings. Conclusions We propose the IEL lymphogram by flow cytometry as an immunological parameter to discern celiac condition from healthy mucosa. This obviates not only misinterpretation of minor histological changes, but also patchiness and the concerns about the location and number of biopsies.
      PubDate: 2014-11-04
  • Effect of Gum Chewing on the Volume and pH of Gastric Contents: A
           Prospective Randomized Study
    • Abstract: Background Insufficient fasting prior to endoscopic procedures performed under sedation may result in potential aspiration of gastric contents. Fasting as per ASA guidelines is recommended prior to these procedures. However, the effect of chewing gum on fasting status has been a subject of debate and often leads to procedural delays. Objective Evaluation of the effect of chewing gum on the gastric volume and pH. Methods In this randomized controlled prospective observer blinded trail, ASA I–III patients aged more than 18 years scheduled for esophagogastroduodenoscopy (EGD) or a combined EGD and colonoscopy under conscious sedation were studied. Patients randomized to the chewing gum group (Group-C) were allowed to chew gum until just before the start of their procedure; the remaining patients were included into Group-NC. After sedation and endoscope insertion, stomach contents were aspirated under vision of a gastroenterologist (blinded to groups). Results Volume and pH of gastric contents aspirated from 67 patients (34 in Group-C and 33 in Group-NC) were analyzed. The demographic parameters of the groups were comparable. Gastric volume (median-interquartile range) was statistically higher in Group-C (13 ml (7.75–40.75) vs Group-NC 6 ml (1.00–14.00) (P < 0.001)]. The mean pH in both groups was comparable: 2.84 ± 2.11 in Group-C and 3.79 ± 2.53 in Group-NC (P = 0.141). Conclusion Although our results show gastric volume in patients chewing gum was statistically higher, clinical relevance of such a small difference is questionable. Thus patients who chewed gum inadvertently prior to procedure should not be denied or delayed administration of sedative and anesthetic medications.
      PubDate: 2014-11-02
  • BPTF Associated with EMT Indicates Negative Prognosis in Patients with
           Hepatocellular Carcinoma
    • Abstract: Background/Aims Epithelial-mesenchymal transition (EMT) plays an important role in hepatocellular carcinoma (HCC) dissemination. Bromodomain PHD-finger transcription factor (BPTF) could regulate embrogenesis and stem cell differentiation, and it may be involved in tumor progression and EMT. In this study, we aimed to determine BPTF, E-cadherin and vimentin expression in tumor tissues and the clinical significance in relation to HCC. Methods The BPTF, vimentin and E-cadherin expression of 106 HCC tissue samples was examined by immunohistochemical staining. Results BPTF and vimentin showed high expression and E-cadherin showed low expression in HCC. BPTF is associated with the tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). Vimentin is positively correlated with tumor size, tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). E-cadherin is negatively correlated with tumor number, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). Survival analysis has shown that high expression of BPTF and vimentin indicates poorer overall and disease-free survival (P < 0.05). Multivariate analysis shows that BPTF is an independent marker for survival prediction (P = 0.015). Additionally, high BPTF expression is correlated with high vimentin expression and low E-cadherin expression (P < 0.05). Conclusion High BPTF expression may be an independent marker for survival prediction in HCC patients and is probably involved in EMT.
      PubDate: 2014-11-02
  • Is It Safer to Postpone Endoscopic Large Balloon Dilatation After ES in
           the Setting of Acute Cholangitis Due to Large Bile Duct Stones'
    • PubDate: 2014-11-01
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