The spectrum of small-bowel lesions of AL-type amyloidosis at capsule endoscopy

n/

Maximizing the general success of cecal intubation during propofol sedation in a multi-endoscopist academic centre

<p>Abstract</p> <p>Background</p> <p>Achieving the target of 95% colonoscopy completion rate at centres conducting colorectal screening programs is an important issue. Large centres and teaching hospitals employing endoscopists with different levels of training and expertise risk achieving worse results. Deep sedation with propofol in routine colonoscopy could maximize the results of cecal intubation.</p> <p>Methods</p> <p>The present study on the experience of a single centre focused on estimating the overall completion rate of colonoscopies performed under routine propofol sedation at a large teaching hospital with many operators involved, and on assessing the factors that influence the success rate of the procedure and how to improve this performance, analyzing the aspects relating to using of deep sedation. Twenty-one endoscopists, classified by their level of specialization in colonoscopic practice, performed 1381 colonoscopies under deep sedation. All actions needed for the anaesthesiologist to restore adequate oxygenation or hemodynamics, even for transient changes, were recorded.</p> <p>Results</p> <p>The "crude" overall completion rate was 93.3%. This finding shows that with routine deep sedation, the colonoscopy completion rate nears, but still does not reach, the target performance for colonoscopic screening programs, at centers where colonoscopists of difference experience are employed in such programs.</p> <p>Factors interfering with cecal intubation were: inadequate colon cleansing, endoscopists' expertise in colonoscopic practice, patients' body weight under 60 kg or age over 71 years, and the need for active intervention by the anaesthesiologist. The most favourable situation - a patient less than 71 years old with a body weight over 60 kg, an adequate bowel preparation, a "highly experienced specialist" performing the test, and no need for active anaesthesiological intervention during the procedure - coincided with a 98.8% probability of the colonoscopy being completed.</p> <p>Conclusions</p> <p>With routine deep sedation, the colonoscopy completion rate nears the target performance for colonoscopic screening programs, at centers where colonoscopists of difference experience are employed in such programs. Organizing the daily workload to prevent negative factors affecting the success rate from occurring in combination may enable up to 85% of incomplete procedures to be converted into successful colonoscopies.</p

Primary uncleansed 2D versus primary electronically cleansed 3D in limited bowel preparation CT-colonography. Is there a difference for novices and experienced readers?

The purpose of this study was to compare a primary uncleansed 2D and a primary electronically cleansed 3D reading strategy in CTC in limited prepped patients. Seventy-two patients received a low-fibre diet with oral iodine before CT-colonography. Six novices and two experienced observers reviewed both cleansed and uncleansed examinations in randomized order. Mean per-polyp sensitivity was compared between the methods by using generalized estimating equations. Mean per-patient sensitivity, and specificity were compared using the McNemar test. Results were stratified for experience (experienced observers versus novice observers). Mean per-polyp sensitivity for polyps 6 mm or larger was significantly higher for novices using cleansed 3D (65%; 95%CI 57–73%) compared with uncleansed 2D (51%; 95%CI 44–59%). For experienced observers there was no significant difference. Mean per-patient sensitivity for polyps 6 mm or larger was significantly higher for novices as well: respectively 75% (95%CI 70–80%) versus 64% (95%CI 59–70%). For experienced observers there was no statistically significant difference. Specificity for both novices and experienced observers was not significantly different. For novices primary electronically cleansed 3D is better for polyp detection than primary uncleansed 2D

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (08,11 and14) account for most of the DRB1 association signal. Consistent with previous studies, DRB108 (P=1.59 710-11) was the strongest predisposing allele, whereas DRB111 (P=1.42 710-10) was protective. Additionally, DRB114 and the DPB1 association (DPB103:01; P=9.18 710-7) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC

Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients

The terroridiom principle between spoken and written discourse

This paper focuses on phraseology used within the domain of politics, both in written and spoken discourse. We concentrate on the lemma terror and on the recurrent sequences in which it is embedded, reflecting how native speakers, both American and British, tend to use it in preferred environments making routinized blocks of language. The data come from two corpora: the spoken corpus includes the speeches of George W. Bush and Tony Blair, and the written corpus is made up of articles from The Wall Street Journal and The Economist. Since text is nothing but phraseology of one kind or another (Sinclair 2005), our attempt here is to uncover which of the two varieties lends itself more willingly to creating phrases that are handled like single units. The two pieces of software used to retrieve n-grams and concgrams are WordSmith Tools (Scott 2004), and ConcGram (Greaves 2005)