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Showing papers by "Javier P. Gisbert published in 2014"


Journal ArticleDOI
TL;DR: Patients with ulcerative colitis have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate.
Abstract: Summary Background Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate. Aim To assess the risk of CRC in UC patients by systematic review and meta-analysis. Methods A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle-Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub-analyses were performed to identify factors associated with an increased risk of developing CRC. Results A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient-years (py) [95% confidence interval (CI), 1.39–1.76]. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population-based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade. Conclusions The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.

202 citations


Reference EntryDOI
TL;DR: Additional endoscopic treatment after epinephrine injection reduces further bleeding, the need for surgery and mortality in patients with bleeding peptic ulcer.
Abstract: Background Endoscopic therapy reduces the rebleeding rate and the need for surgery in patients with bleeding peptic ulcers. Objectives To determine whether a second procedure improves haemostatic efficacy or patient outcomes or both after epinephrine injection in adults with high-risk bleeding ulcers. Search methods For our update in 2014, we searched the following versions of these databases, limited from June 2009 to May 2014: Ovid MEDLINE(R) 1946 to May Week 2 2014; Ovid MEDLINE(R) Daily Update May 22, 2014; Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations May 22, 2014 (Appendix 1); Evidence-Based Medicine (EBM) Reviews—the Cochrane Central Register of Controlled Trials (CENTRAL) April 2014 (Appendix 2); and EMBASE 1980 to Week 20 2014 (Appendix 3). Selection criteria We included randomised controlled trials (RCTs) comparing epinephrine alone versus epinephrine plus a second method. Populations consisted of patients with high-risk bleeding peptic ulcers, that is, patients with haemorrhage from peptic ulcer disease (gastric or duodenal) with major stigmata of bleeding as defined by Forrest classification Ia (spurting haemorrhage), Ib (oozing haemorrhage), IIa (non-bleeding visible vessel) and IIb (adherent clot) (Forrest Ia-Ib-IIa-IIb). Data collection and analysis We used standard methodological procedures as expected by The Cochrane Collaboration. Meta-analysis was undertaken using a random-effects model; risk ratios (RRs) with 95% confidence intervals (CIs) are presented for dichotomous data. Main results Nineteen studies of 2033 initially randomly assigned participants were included, of which 11 used a second injected agent, five used a mechanical method (haemoclips) and three employed thermal methods. The risk of further bleeding after initial haemostasis was lower in the combination therapy groups than in the epinephrine alone group, regardless of which second procedure was applied (RR 0.53, 95% CI 0.35 to 0.81). Adding any second procedure significantly reduced the overall bleeding rate (persistent and recurrent bleeding) (RR 0.57, 95% CI 0.43 to 0.76) and the need for emergency surgery (RR 0.68, 95% CI 0.50 to 0.93). Mortality rates were not significantly different when either method was applied. Rebleeding in the 10 studies that scheduled a reendoscopy showed no difference between epinephrine and combined therapy; without second-look endoscopy, a statistically significant difference was observed between epinephrine and epinephrine and any second endoscopic method, with fewer participants rebleeding in the combined therapy group (nine studies) (RR 0.32, 95% CI 0.21 to 0.48). For ulcers of the Forrest Ia or Ib type (oozing or spurting), the addition of a second therapy significantly reduced the rebleeding rate (RR 0.66, 95% CI 0.49 to 0.88); this difference was not seen for type IIa (visible vessel) or type IIb (adherent clot) ulcers. Few procedure-related adverse effects were reported, and this finding was not statistically significantly different between groups. Few adverse events occurred, and no statistically significant difference was noted between groups. The addition of a second injected method reduced recurrent and persistent rebleeding rates and surgery rates in the combination therapy group, but these findings were not statistically significantly different. Significantly fewer participants died in the combined therapy group (RR 0.50, 95% CI 0.25 to 1.00). Epinephrine and a second mechanical method decreased recurrent and persistent bleeding (RR 0.31, 95% CI 0.18 to 0.54) and the need for emergency surgery (RR 0.20, 95% CI 0.06 to 0.62) but did not affect mortality rates. Epinephrine plus thermal methods decreased the rebleeding rate (RR 0.49, 95% CI 0.30 to 0.78) and the surgery rate (RR 0.20, 95% CI 0.06 to 0.62) but did not affect the mortality rate. Our risk of bias estimates show that risk of bias was low, as, although the type of study did not allow a double-blind trial, rebleeding, surgery and mortality were not dependent on subjective observation. Although some studies had limitations in their design or implementation, most were clear about important quality criteria, including randomisation and allocation concealment, sequence generation and blinding. Authors' conclusions Additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer. The main adverse events include risk of perforation and gastric wall necrosis, the rates of which were low in our included studies and favoured neither epinephrine therapy nor combination therapy. The main conclusion is that combined therapy seems to work better than epinephrine alone. However, we cannot conclude that a particular form of treatment is equal or superior to another.

172 citations


Journal ArticleDOI
TL;DR: Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population and the number of older patients diagnosed with IBD is expected to increase in the coming years.
Abstract: Summary Background Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population. Aim To critically review available data regarding the care of elderly IBD patients. Methods Bibliographic searches (MEDLINE) up to June 2013. Results Approximately 10–15% of cases of IBD are diagnosed in patients aged >60 years, and 10–30% of the IBD population are aged >60 years. In the elderly, IBD is easily confused with other more common diseases, mainly diverticular disease and ischaemic colitis. The clinical features of IBD in older patients are generally similar to those in younger patients. Crohn's disease (CD) in elderly patients is characterised by its predominantly colonic localisation and uncomplicated course. Proctitis and left-sided ulcerative colitis are more common in patients aged >60 years. Infections are associated with age and account for significant mortality in IBD patients. The treatment of IBD in the elderly is generally similar. However, the therapeutic approach in the elderly should be ‘start low-go slow’. The benefit of thiopurines in older CD patients remains debatable. Although the indications for anti-tumour necrosis factors in the elderly are generally similar to those for younger patients, lower response and higher adverse events have been reported in the elderly. Surgery in elderly patients does not generally differ. Ileal pouch-anal anastomosis can be successful, provided the patient retains good anal sphincter function. Conclusions Management of the older IBD patient differs from that of younger patients; therefore, conventional practice algorithms may have to be modified to account for advanced age.

129 citations


Journal ArticleDOI
01 Feb 2014-Gut
TL;DR: Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates, and both therapies showed an acceptable safety profile.
Abstract: Objectives No trial has compared non-bismuth quadruple ‘sequential’ and ‘concomitant’ regimens in settings with increasing clarithromycin rates. The study aims to compare the effectiveness and safety of these therapies for Helicobacter pylori treatment. Design Prospective randomised clinical trial in 11 Spanish hospitals. Patients naive to eradication therapy with non-investigated/functional dyspepsia or peptic ulcer disease were included. Randomised (1:1) to sequential (omeprazole (20 mg/12 h) and amoxicillin (1 g/12 h) for 5 days, followed by 5 days of omeprazole (20 mg/12 h), clarithromycin (500 mg/12 h) and metronidazole (500 mg/12 h)), or concomitant treatment (same drugs taken concomitantly for 10 days). Eradication was confirmed with 13 C-urea breath test or histology 4 weeks after treatment. Adverse events (AEs) and compliance were evaluated with questionnaires and residual medication count. Results 338 consecutive patients were randomised. Mean age was 47 years, 60% were women, 22% smokers and 20% had peptic ulcer. Concomitant and sequential eradication rates were, respectively, 87% vs 81% by intention-to-treat (p=0.15) and 91% vs 86% (p=0.131) per protocol. Respective compliances were 83% vs 82%. Treatment-emergent AEs were reported in 59% of patients (no differences found between treatments). AEs were mostly mild (60%), and average length was 6.1 days, causing discontinuation only in 12 patients. Multivariate analysis: ‘concomitant’ treatment showed an OR of 1.5 towards better eradication rate in a borderline significance CI (95% CI 0.9 to 2.8). Conclusions Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates. Both therapies showed an acceptable safety profile. ClincialTrials.gov NCT01273441.

127 citations



Journal ArticleDOI
TL;DR: A novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates is provided.
Abstract: The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.

62 citations


Journal ArticleDOI
TL;DR: The results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.
Abstract: The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

48 citations


Journal ArticleDOI
TL;DR: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.
Abstract: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI–amoxicillin–levofloxacin still fails in >20 % of patients. To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. Prospective multicenter study of patients in whom 1st treatment with PPI–clarithromycin–amoxicillin and 2nd with PPI–amoxicillin–levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by 13C-urea-breath-test 4–8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60–74 %) and 65 % (58–72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

47 citations


Journal ArticleDOI
TL;DR: A role of TNFRSF1B gene variants in the response to IFX in CD patients is supported, supported by the results of a replicate of the association described in the Japanese population.

44 citations


Journal ArticleDOI
TL;DR: The accuracy of GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended.
Abstract: BACKGROUND It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies. AIM To determine the accuracy of GastroPanel for the diagnosis of CAG. METHODS This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist. RESULTS Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 μg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios. CONCLUSION GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended.

42 citations


Journal ArticleDOI
TL;DR: Young patients vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed better response, and following-up the established surveillance and/or preventive anti-viral therapy seems to be safe in HBV and HCV patients.

Journal ArticleDOI
TL;DR: Angiopoietins have key functions in the angiogenic process, and their abnormal activation might depend on their surrounding inflamed environment, which could be useful for monitoring IBD progression.

Journal ArticleDOI
TL;DR: Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
Abstract: This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.

Journal ArticleDOI
TL;DR: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD, which should be taken into account at establishing predictors of disease course.


Journal ArticleDOI
TL;DR: Familial IBD is associated with diagnostic anticipation in younger individuals and Familial history does not allow predicting any phenotypic feature other than IBD type, and there was no relevant concordance for any of the phenotypesic items assessed in both diseases.

Journal ArticleDOI
TL;DR: Circulating VEGF and Ang1 levels decrease after anti–TNF-alpha therapy and may predict response to treatment and whether these changes are a direct effect of anti– TNF- alpha therapy or a sign of disease improvement remains to be elucidated.
Abstract: BACKGROUND Infliximab and adalimumab effectiveness might be related with changes in angiogenic factors. The aim of the study was to compare the concentrations of angiogenic proteins in patients with inflammatory bowel disease (IBD) and healthy controls and to analyze changes in the levels during infliximab and adalimumab treatment. METHODS A prospective case-control study was conducted in 37 patients with IBD starting treatment with infliximab (16 with Crohn's disease and 6 with ulcerative colitis) or adalimumab (15 with Crohn's disease) and 40 control subjects. Four samples were taken from IBD patients, one before each of the first 3 doses of infliximab/adalimumab and one at week 14. Serum levels of vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 1 (Ang1), angiopoietin 2, and Tie2 were measured using enzyme-linked immunosorbent assay. RESULTS Patients with IBD had higher VEGF levels than control subjects (511.5 ± 255.6 versus 395.5 ± 256.4; P = 0.05). Patients who achieved remission at the third dose of anti-TNF-alpha had lower VEGF levels at baseline (453.5 ± 250.7 versus 667.5 ± 153.9 pg/mL) and before the second (409.7 ± 217 versus 681.3 ± 350.6 pg/mL) and third (400.5 ± 222.8 versus 630.4 ± 243.1 pg/mL) doses compared with those with no remission (P < 0.05). Ang1 levels decreased before each treatment dose in patients who achieved remission (P < 0.05). High baseline VEGF levels predicted for a poor response to anti-TNF-alpha therapy (area under the receiver operating characteristics curve = 0.8), whereas high Ang1 levels were associated with disease remission (area under the receiver operating characteristics curve = 0.7). Concentrations of angiogenic proteins did not correlate with clinical activity scores. CONCLUSIONS Circulating VEGF and Ang1 levels decrease after anti-TNF-alpha therapy and may predict response to treatment. Whether these changes are a direct effect of anti-TNF-alpha therapy or a sign of disease improvement remains to be elucidated.

Journal ArticleDOI
TL;DR: Frequency of listening and enjoyment were significantly correlated and active participation in musical activities, specifically singing, resulted in significantly higher overall performance scores.
Abstract: Objectives To document musical listening and enjoyment in recipients of Advanced Bionics cochlear implants (CIs) and to compare musical perception in those using early coding strategies with subjects using the newer HiRes and HiRes 120 strategies. Methods A questionnaire was completed by 136 adult subjects, including questions on the ability to identify specific musical features. The subjects were in three groups: those using early coding strategies (n = 29), HiRes (n = 59), and HiRes 120 (n = 48), and results were compared with a group of 84 normally hearing (NH) subjects. Results Of the CI users, 79% reported listening to music. The NH group rated listening frequency and enjoyment higher than the CI users. Thirty-five users reported that they sang and this group had significantly higher overall performance. There were no significant differences in overall perception of specific musical features among the strategy groups, though some individual questions showed significantly higher performance in the HiR...

Journal ArticleDOI
TL;DR: Infliximab appears to be safe for the mother with IBD and the newborn, at least in the short-term, and is transferred in breast milk; although its toxicity is unlikely, it cannot be discounted without further long-term data.
Abstract: Introduction: Infliximab has been approved for the treatment of patients with inflammatory bowel diseases (IBD). However, data regarding its safety during pregnancy and breastfeeding are scarce.Areas covered: Relevant papers sourced from bibliographical searches (MEDLINE) up to June 2014 are reviewed. Infliximab, as adalimumab, crosses the placenta from the end of the second trimester. The use of anti-TNF agents after the second trimester leads to intrauterine exposure. Although infliximab during pregnancy in IBD patients seems to be safe in the short-term, there are concerns about the consequences of the early exposition with this drug for the development of the newborn immune system. Accordingly, it has recently been suggested that anti-TNF drugs should be stopped during, at least, the second trimester, when the mother is in remission; this approach seems to be safe for the mother and minimizes fetal exposition to the drug. Infliximab has been detected in breast milk in miniscule amounts. Case reports d...


Journal ArticleDOI
TL;DR: The results confirm that the number of patients with inflammatory bowel disease (IBD) who develop depression is higher than the average in the general population, and higher depression rates in patients with a more aggressive disease phenotype are reported.
Abstract: This is a very interesting well-designed study. The results confirm that the number of patients with inflammatory bowel disease (IBD) who develop depression is higher than the average in the general population. In this study, the authors report, as expected, higher depression rates in patients with a more aggressive disease phenotype. Some studies previously showed a clear association between depression and disease relapse, 2 but in a study performed in patients with Crohn 0 s disease (CD), 24% maintained depressive symptoms in spite of having been in remission for more than 6 months. 3 This means that while physicians think that clinical remission is enough, in fact some patients may need more help in order to make a full recovery. With that in mind, perhaps we should try to include psychological stabilization among the treatment objectives? Some years ago, health-related quality of life (HRQOL) was barely evaluated in clinical trials and studies, but recently, restoring HRQOL in IBD patients

Journal ArticleDOI
TL;DR: Los diagnosticos se recogieron de forma transversal de la historia clinica en el momento of incorporar a cada paciente al estudio, y las variables asociadas a the presencia of EIMI fueron el diagnostico de EC, un tiempo de evolucion of the EII and morelos de ≥ 4 anos frente a Conclusiones.

Journal ArticleDOI
TL;DR: The most effective second-line treatments after the failure of a first-line therapy with PPI, amoxicillin and clarithromycin in H. pylori eradication are the metronidazole-amoxicillin-PPI or a 10 days levofloxacin-am toxicillin- PPI therapy.

Journal ArticleDOI
TL;DR: Although it is agreed anti-viral treatment might favourably impact UC course in some patients with refractory disease and very high viral load, the study shows that for the majority of patients, it does not impact clearly on the course of UC.
Abstract: recent article, and acknowledge the lack of clear definition for clinically significant cytomegalovirus (CMV) reactivation. 2 The European Crohn’s and Colitis Organisation guidelines recommend CMV polymerase chain reaction (PCR) on colonic mucosa to detect CMV reactivation in ulcerative colitis (UC) patients. However, as CMV has been shown to have a tropism for inflamed tissue, and is detected in UC patients up to 20 times more often than in the general population, we raise the concern of the clinical relevance of tissue PCR. Positive CMV PCR on colonic biopsies has been associated with steroid refractoriness suggesting it could represent a marker of severity. However, no controlled data support a positive effect of anti-viral treatment in inflammatory bowel disease patients with CMV reactivation. In our study, among 33 UC patients with positive CMV PCR on colonic biopsies, similar outcomes were observed, with or without anti-viral treatment. We agree that we did not evaluate the impact of antiviral treatment on CMV reactivation in the specific population of UC patients’ refractory to steroid therapy. Different studies have suggested a favourable impact of anti-viral treatment in this setting. 7 Yet we note that some of these patients not given anti-viral treatment still achieved remission. A randomised control trial comparing anti-viral treatment with placebo in steroid-refractory UC patients with CMV reactivation has yet to be conducted. Although we agree anti-viral treatment might favourably impact UC course in some patients with refractory disease and very high viral load, we think our study shows that for the majority of patients, it does not impact clearly on the course of UC. Given the potential serious side effects associated with anti-viral treatment, we think its generalised use should not be recommended and patients who benefit best from it should be more clearly defined.

Journal ArticleDOI
TL;DR: Results from all available prospective adult studies on this issue are fully consistent and will certainly convince the scientific community of the existence of PPI-responsive oesophageal eosinophilia, as shown in consensus guidelines.
Abstract: Vazquez Elizondo et al. report the largest prospective series to date addressing the rate of responsiveness to proton pump inhibitor (PPI) therapy in 60 symptomatic patients with oesophageal eosinophilic infiltration [>15 eosinophils per high power field (HPF)]. PPI therapy led to clinical improvement in 71% of patients, and eosinophil counts <15 per HPF in 56.6%. Using more stringent criteria, complete clinical response coupled with complete histological remission (<5 eosinophils per HPF) was accomplished in 36% of patients. Of note, complete histological remission was significantly higher in patients with a gastro-oesophageal reflux disease (GERD) phenotype (71%), compared with those with an eosinophilic oesophagitis phenotype (35%). These important findings strongly support the need for a PPI trial before giving a diagnosis of eosinophilic oesophagitis, as stated in recent consensus guidelines, 3 given the fact that a substantial proportion of adult patients with suspected eosinophilic oesophagitis can be managed without topical steroids or dietary interventions. Furthermore, the results by Vazquez Elizondo et al. are almost identical to those reported in the first prospective adult series published 2 years ago (75% response in patients with upper gastrointestinal symptoms and 50% response with an eosinophilic oesophagitis phenotype), and in the first systematic review on PPI-responsive oesophageal eosinophilia (at least 33% of PPI responders and 70% response with documented GERD), published some months ago. Initial scepticism on PPI-responsive oesophageal eosinophilia possibly came from the assumption of a rigid distinction between GERD and eosinophilic oesophagitis and mixed data, as discussed by Vazquez Elizondo et al., including retrospective series in children, prospective series in adults and comparative trials. Collectively, results from all available prospective adult studies on this issue 4, 6–8 (Table 1), from Europe and the USA, are fully consistent and will certainly convince the scientific community of the existence of PPI-responsive oesophageal eosinophilia, as shown in consensus guidelines. 3

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TL;DR: The optimized regimen is more effective than the standard one and the incidence of adverse effects is higher with the optimized treatment, but these are mostly mild, and do not negatively impact the compliance.

Journal ArticleDOI
TL;DR: Rats with colitis showed an increase in oxidised serum albumin levels and in the oxidation of colon mucous cells and both decreased after IFX treatment, suggesting that oxidised albumin could be a useful biomarker for monitoring inflammatory bowel disease.
Abstract: Infliximab (IFX) is widely used in ulcerative colitis and in Crohn’s disease treatment. Both diseases are characterised by increased oxidative stress, which may affect albumin oxidation. In order to test this hypothesis, the effect of IFX on colitis induced by dextran sulphate sodium (DSS) in rats was evaluated by measuring the Disease Activity Index, biochemical parameters, serum albumin oxidation and colonic mucosa oxidation. Rats with colitis showed an increase in oxidised serum albumin levels and in the oxidation of colon mucous cells. Both decreased after IFX treatment. This suggests that oxidised albumin could be a useful biomarker for monitoring inflammatory bowel disease.

Journal ArticleDOI
TL;DR: A significant proportion of patients with Crohn's disease suffer from folate deficiency, suggesting that regular screening should be performed.
Abstract: Folate deficiency in patients with Crohn's disease may be due to a combination of factors: poor diet, malabsorption, increased requirements due to inflammation of the mucosa, and the taking of certain drugs as sulfasalazine and methotrexate. A significant proportion of patients with Crohn's disease suffer from folate deficiency, suggesting that regular screening should be performed.

Journal ArticleDOI
TL;DR: Japanese is below Westerners in the ratio of homo-EM as well as RPZ based triple therapy without relation to CYP2C19 genotype, in Japan, and there was negative effect on eradication rates.

Journal ArticleDOI
TL;DR: This work has shown that a variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus and the outcome of IFN therapy for chronic hepatitis C.
Abstract: 1. Galmozzi E, Lampertico P. Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks? Aliment Pharmacol Ther 2014; 39: 548–9. 2. St€attermayer AF, Strassl R, Maieron A, et al. Polymorphism of interferon-k and IL28B – effects on treatment response to interferon/ribavirin in patients with chronic hepatitis C. Aliment Pharmacol Ther 2014; 39: 104–11. 3. Hamming OJ, Terczynska-Dyla E, Vieyres G, et al. Interferon lambda 4 signals via the IFNk receptor to regulate antiviral activity against HCV and coronaviruses. EMBO J 2013; 32: 3055–65. 4. Honda M, Sakai A, Yamashita T, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 2010; 139: 499–509. 5. Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013; 45: 164–71. 6. Abe H, Hayes CN, Ochi H, et al. IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy. J Hepatol 2011; 54: 1094–101.