Insulin Resistance Impairs Viral Dynamics Independently of Ethinicity or Genotypes.
J Clin Gastroenterol. 2012 Jan 30;
Authors: Eslam M, Aparcero R, Mousa YI, Grande L, Shaker Y, Ali A, Del Campo JA, Khattab MA, Romero-Gomez M
Abstract
BACKGROUND AND AIM:: Data concerning the influence of insulin resistance (IR) and ethnicity on early phases of viral kinetics after initiation of peginterferon plus ribavirin in treatment-naive, chronic hepatitis C (CHC) patients are limited. METHODS:: A total of 263 nondiabetic CHC patients treated with peginterferon plus ribavirin were enrolled for analysis from an Egyptian and Spanish center. IR was evaluated by homeostasis model assessment (HOMA)-IR. Hepatitis C virus (HCV) RNA levels were measured at baseline, 48 hours, 2, 4, and 12 weeks after treatment initiation. Sustained virological response (SVR) was examined 24 weeks after therapy discontinuation. RESULTS:: Baseline HOMA-IR strongly influenced 48 hours viral dynamics. HCV-RNA decay observed at 48 hours after the first injection of peginterferon was significantly lower (0.91±0.51 log) in patients with HOMA ≥2 compared with those with HOMA <2 (1.8±0.95 log, P=0.005) this effect was independent of stage of liver fibrosis, HCV genotype, and ethnicity. These differences remained with several cutoffs such as HOMA >3 or HOMA >4. Multivariate analysis identified baseline insulin levels as the main independent variable affecting the 48-hour response in addition to baseline HCV-RNA. The difference in early viral kinetics between patients with HOMA ≥2 or <2 is associated with a significant difference in the percentage of patients achieving both rapid virological response and SVR. CONCLUSIONS:: IR is a major determinant of the early viral kinetic response to peginterferon plus ribavirin, which has a great impact on subsequent rapid virological response and SVR in CHC patients. This suggests that strategies to improve IR may have a positive effect on SVR and may be early monitored.
PMID: 22298085 [PubMed - as supplied by publisher]
BACKGROUND:: Refractory celiac disease (RCD) is a preneoplastic condition as many patients develop an enteropathy-type T-cell lymphoma, a mature T-cell receptor α-β lymphoma arising in the gut with an ominous outcome. Recently, research focused on a population of intraepithelial intestinal lymphocytes expressing the same lymphoma T-cell receptor variable region (V)γ, as shown by polymerase chain reaction (PCR) analysis and sequencing. Meanwhile, the Biomedicine and Health-2 Concerted Action has made available standardized, highly specific, and sensitive PCR assays not only for Vγ but also for Vβ. GOALS:: We verified whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method. STUDY:: Duodenal biopsies were analyzed from 15 RCD patients, 21 negative controls, and 2 positive controls (enteropathy-type T-cell lymphoma complicating celiac disease). Multiplex clonality analyses were performed according to the Biomedicine and Health-2 protocols. PCR products were cloned and sequenced. RESULTS:: Monoclonal rearrangements were found in 5/15 samples from patients with RCD (both rearrangements in 2 cases, Vβ only in 2, and only 1 solitary Vγ clonality). Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results. CONCLUSIONS:: The combined analysis of both rearrangements allowed recognition of monoclonal populations in otherwise negative patients, with detection rates from 20% (Vγ only) to 33% (Vγ and Vβ), thus raising the likelihood of early identification of RCD patients at high risk of death.
PMID: 22298086 [PubMed - as supplied by publisher]
Second-look Endoscopy for Bleeding Peptic Ulcer Disease: A Decision-effectiveness and Cost-effectiveness Analysis.
J Clin Gastroenterol. 2012 Jan 30;
Authors: Imperiale TF, Kong N
Abstract
BACKGROUND:: Second-look endoscopy after initial therapeutic endoscopy for bleeding peptic ulcer disease may decrease the risk of rebleeding; however, it is not recommended routinely. Understanding conditions under which second-look endoscopy is beneficial might be useful for clinical decision making. METHODS:: Using a decision model, literature-based probabilities, and Medicare reimbursement costs, we compared routine second-look endoscopy with no second-look endoscopy. We measured rebleeding, need for surgery, hospital mortality, and costs, and calculated the cost to avoid each outcome, expressed as the number needed to treat, along with the cost per outcome prevented. RESULTS:: In the base case, routine second-look endoscopy reduced rebleeding from 16% to 10% (needed to treat=16) but had no effect on other outcomes. The cost to prevent 1 case of rebleeding was nearly $13,000. Threshold analysis revealed a rebleeding threshold of 31% to neutralize the cost difference between routine second-look endoscopy and no routine second-look endoscopy. If routine second-look endoscopy was 100% effective in preventing rebleeding, then the rebleeding threshold for cost neutrality would be 17.5%. When rebleeding risks after the index endoscopy and second-look endoscopy were simultaneously considered, the cost per bleed prevented ranged from a cost savings of $165 when the respective risks were 25% and 5%, to a cost of nearly $33,000 when the risks were 20% and 15%. CONCLUSIONS:: The results suggest that routine second-look endoscopy is not indicated after therapeutic endoscopy for bleeding peptic ulcer disease. However, if rebleeding risk is 31% or greater, then routine second-look endoscopy reduces this risk at no additional cost.
PMID: 22298087 [PubMed - as supplied by publisher]
Long-Term Clinical Outcomes and Factors Predictive of Relapse After 5-Aminosalicylate or Sulfasalazine Therapy in Patients With Intestinal Behcet Disease.
J Clin Gastroenterol. 2012 Jan 30;
Authors: Jung YS, Hong SP, Kim TI, Kim WH, Cheon JH
Abstract
BACKGROUND:: Currently, 5-aminosalicylic acid (5-ASA)/sulfasalazine is used to empirically treat patients with intestinal Behcet disease (BD) without clear clinical evidence. In this study, we investigated long-term clinical outcomes and predictors of clinical relapse in patients with intestinal BD receiving 5-ASA/sulfasalazine maintenance therapy. METHODS:: We reviewed the medical records of all the patients with intestinal BD, who received 5-ASA/sulfasalazine therapy in a single tertiary academic medical center between March 1986 and January 2011. The cumulative probabilities of clinical relapse after remission were calculated using the Kaplan-Meier method. Predictors of clinical relapse were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. RESULTS:: Among the 143 patients enrolled, 46 (32.2%) had a clinical relapse while they were being treated with 5-ASA/sulfasalazine therapy. The cumulative relapse rates at 1, 3, 5, and 10 years after remission were 8.1%, 22.6%, 31.2%, and 46.7%, respectively. By multivariate analysis, a younger age (<35 y) at the time of diagnosis, higher C-reactive protein level (≥1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (≥60) at the time of 5-ASA/sulfasalazine initiation were independent predictors of relapse in patients with intestinal BD receiving 5-ASA/sulfasalazine maintenance therapy. CONCLUSIONS:: This study has shown that 5-ASA/sulfasalazine therapy has a positive effect in maintaining remission in patients with intestinal BD. However, a younger age (<35 y), higher C-reactive protein level (≥1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (≥60) were associated with a poor response to 5-ASA/sulfasalazine therapy, making careful observation and intensive treatment necessary in these risk groups.
PMID: 22298088 [PubMed - as supplied by publisher]
Proton Pump Inhibitor Use and Recurrent Clostridium difficile-associated Disease: A Case-control Analysis Matched by Propensity Score.
J Clin Gastroenterol. 2012 Jan 30;
Authors: Kim YG, Graham DY, Jang BI
Abstract
BACKGROUND AND AIM:: Clostridium difficile has been increasingly diagnosed in hospitalized patients. An association between proton pump inhibitors (PPIs) use and Clostridium difficile-associated disease (CDAD) and between recurrent CDAD has been suggested. The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD. METHODS:: This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center, seen from January 2004 to December 2008. C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool. Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score. RESULTS:: Recurrent CDAD developed in 28 (14.1%) of the 198 patients with diarrhea and positive C. difficile stool toxin assays. Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy (concomitant with the treatment or after or both), poor response to therapy with metronidazole or vancomycin, and recent gastrointestinal surgery were risk factors for recurrent CDAD. We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD. Among the matched patients only PPI use was associated with recurrent CDAD (ie, 47.6% vs. 4.8%, P=0.004 for recurrent vs. nonrecurrent CDAD, respectively). CONCLUSIONS:: Among the matched patient groups, only PPI therapy was associated with recurrent CDAD. Prospective studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea.
PMID: 22298089 [PubMed - as supplied by publisher]
Association of Helicobacter pylori dupA With the Failure of Primary Eradication.
J Clin Gastroenterol. 2012 Jan 30;
Authors: Shiota S, Nguyen LT, Murakami K, Kuroda A, Mizukami K, Okimoto T, Kodama M, Fujioka T, Yamaoka Y
Abstract
GOALS:: To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy. BACKGROUND:: Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure. STUDY:: The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses. RESULTS:: Among 142 strains, 44 (31.0%) were dupA positive. There was no association between dupA status and gastroduodenal diseases (P>0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4% vs. 35.7%, P=0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3% vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than dupA-negative H. pylori (P=0.04). In multivariate analysis adjusted for age, sex, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio=3.71; 95% confidence interval,1.07-12.83). CONCLUSIONS:: Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure.
PMID: 22298090 [PubMed - as supplied by publisher]
We report the first published case of agranulocytosis induced by omeprazole and its recurrence with esomeprazole, the S-isomer form of omeprazole. Interestingly, we found an homozygotous mutation of CYP2C19*17, responsible for the metabolism of proton pump inhibitors.
PMID: 22240865 [PubMed - as supplied by publisher]
Analysis of Intersegmental Trough and Proximal Latency of Smooth Muscle Contraction Using High-Resolution Esophageal Manometry.
J Clin Gastroenterol. 2012 Jan 10;
Authors: Kumar N, Porter RF, Chanin JM, Gyawali CP
Abstract
BACKGROUND AND AIMS:: Intersegmental troughs (ISTs) between striated and smooth muscle contraction segments on high-resolution manometry (HRM) have been linked to hypomotility disorders. We investigated the relationship between ISTs, latency of initiation of smooth muscle contraction, and motor patterns in symptomatic patients and normal controls. METHODS:: HRM Clouse plots were analyzed in 199 participants (47.2±1.2 y, 112F/87M), categorized into 110 participants with gastroesophageal reflux disease (GERD), 74 symptomatic participants without GERD, and 15 healthy controls. IST length was measured in centimeters and percentage esophageal length, designated extended when ≥20% esophageal length on >30% swallows. Proximal latency was measured as the time interval between onset of skeletal and smooth muscle contraction segments, and designated prolonged when ≥4s in ≥50% of swallows. RESULTS:: ISTs of any length were noted in 74.6% swallows and in 92.5% of participants, with a similar frequency across the 3 groups. ISTs and proximal latency were both longer in the GERD group, especially when Barrett esophagus was present, compared with non-GERD patients or controls (P≤0.03 across groups); extended IST and prolonged proximal latency followed similar trends. On multivariate logistic regression, extended IST predicted GERD [odds ratio (OR), 2.30; 95% confidence intervals (CI) 1.18-4.47], as did lower esophageal sphincter pressure <5 mm Hg (OR, 3.79-3.96; 95% CI 1.77-8.49), after controlling for age and sex; prolonged proximal latency predicted both GERD (OR, 2.03; 95% CI 1.01-4.12) and Barrett esophagus (OR 1.91, 95% CI 1.24-2.94). CONCLUSIONS:: Measurement of IST and proximal latency add value to HRM analysis, and may be markers of esophageal hypomotility.
PMID: 22240866 [PubMed - as supplied by publisher]
There have been recent concerns about the safety of proton pump inhibitors (PPIs). We focus here on 3 specific concerns-the possible interaction between PPIs and clopidogrel, the postulated link between PPI use and fractures, and the possibility that long-term PPI use might lead to hypomagnesemia. There is evidence for an in vitro interaction between clopidogrel and at least some PPIs. The Food and Drug Administration (FDA) has warned against the use of certain PPIs by patients on clopidogrel. However, a randomized controlled trial that compared clopidogrel alone with the combination of clopidogrel and omeprazole found no increase in adverse cardiovascular outcomes and a reduction in the rate of adverse gastrointestinal outcomes attributable to omeprazole. PPI use may be a weak risk factor for certain fractures, but the quality of evidence is relatively poor and there is a strong possibility of confounding. The mechanism whereby PPI use might increase fracture risk is unknown. Currently, no additional measures concerning calcium supplementation or bone mineral density monitoring are recommended for patients on a PPI. The FDA has suggested monitoring serum magnesium levels in patients on PPI therapy. The mechanism and frequency of PPI-induced hypomagnesemia are unclear. PPI treatment should not be withheld from patients who genuinely require it, but the PPI should be taken in the lowest effective dose and only for as long as clinically indicated. The same is, of course, true for all medicines. The benefits of PPI therapy greatly outweigh the risks.
PMID: 22227731 [PubMed - in process]
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