Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Transglutaminase-3 Enzyme: A Putative Actor in Human Hair Shaft Scaffolding?

The family of transglutaminases (TGase) is known to be involved in terminal differentiation processes in the epidermis. These enzymes contribute also to the physical resistance and the preservation of the hair follicle structure. Our particular interest in hair fiber keratinization led us to focus on the TGase 3, exclusively expressed in the hair shaft. To date its function is still to be elucidated, thus we have developed a multidisciplinary approach in order to define the localization, activity, and substrates of TGase 3. The hair fiber is characterized by the expression of specific proteins essentially consisting of keratin intermediate filaments and keratin-associated proteins (KAPs), which are essential for the formation of a rigid hair shaft through their extensive disulfide cross-links. Gel electrophoresis combined with mass spectrometry experiments revealed an unexpected protein migration pattern, suggesting the existence of covalent interactions other than disulfide bonds. Western blot and amino-acid analysis revealed the presence of γ-glutamyl-ε-lysine isopeptide linkages that could constitute this second covalent network. Our hypothesis is that TGase 3-driven specific isopeptide bonds between intermediate filaments and KAPs participate to the progressive scaffolding of the hair shaft

Relationship between rectal sensitivity, symptoms intensity and quality of life in patients with irritable bowel syndrome.: rectal sensitivity, IBS severity and QoL

International audienceBACKGROUND: Relationships between pain threshold during rectal distension and both symptoms intensity and alteration in quality of life (QoL) in irritable bowel syndrome (IBS) patients have been poorly evaluated. AIM: To evaluate relationships between rectal sensitivity, IBS symptom intensity and QoL in a multicentre prospective study. METHODS: Rectal threshold for moderate pain was measured during rectal distension in IBS patients (Rome II), while IBS symptoms intensity was assessed by a validated questionnaire and QoL by the Functional Digestive Disorder Quality of Life questionnaire. RESULTS: Sixty-eight patients (44.2 +/- 12.7 years, 48 women) were included. The mean rectal distending volume for moderate pain was 127 +/- 35 mL while 45 patients (66%) had rectal hypersensitivity (pain threshold <140 mL). Rectal threshold was not significantly related either to overall IBS intensity score (r = -0.66, P = 0.62) or to its different components, or to FDDQL score (r = 0.30, P = 0.14). Among FDDQL domains, only anxiety (r = 0.30, P = 0.01) and coping (r = 0.31, P = 0.009) were significantly related with pain threshold. CONCLUSIONS: In this study, two-thirds of IBS patients exhibited rectal hypersensitivity. No significant correlation was found between rectal threshold and either symptom intensity or alteration in QoL

SmartPulse, a machine learning approach for calibration-free dynamic RF shimming: preliminary study in a clinical environment

International audiencePurpose: A calibration-free pulse design method is introduced to alleviate B$_1$$^+$ artifacts in clinical routine with parallel transmission at high field, dealing with significant inter-subject variability, found for instance in the abdomen.Theory and Methods: From a dual-transmit 3T scanner, a database of B$_1$$^+$ and off resonance abdominal maps from 50 subjects was first divided into three clusters based on mutual affinity between their respective tailored kT-points pulses. For each cluster, a kT-points pulse was computed, minimizing normalized root-mean-square flip angle (FA) deviations simultaneously for all subjects comprised in it. Using 30 additional subjects’ field distributions, a machine learning classifier was trained on this 80-labelled-subject database to recognize the best pulse from the three ones available, relying only on patient features accessible from the preliminary localizer sequence present in all protocols. This so-called SmartPulse process was experimentally tested on an additional 53-subject set and compared with other pulse types: vendor’s hard calibration-free dual excitation, tailored static RF shimming, universal and tailored kT-points pulses.Results: SmartPulse outperformed both calibration-free approaches. Tailored static RF shimming yielded similar FA homogeneity for most patients but broke down for some while SmartPulse remained robust. Although FA homogeneity was systematically better with tailored kT-points, the difference was barely noticeable on in-vivo images.Conclusion: The proposed method paves the way towards an efficient trade-off between tailored and universal pulse design approaches for large inter-subject variability. With no need for on-line field mapping or pulse design, it can fit seamlessly into a clinical protocol

Expectations of IBS patients concerning disease and healthcare providers: Results of a prospective survey among members of a French patients’ association

International audienceBackground and aimsIBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients’ organization.Patients and methodsFrom January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP.Results222/330 (67%) responded (women: 68.5%, 46.5 ± 17.7 years, disease duration: 8.8 ± 0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS > 300 in 53% and HAD score > 19 in 45%). QoL impairment was correlated with disease severity and HAD score (r = −0.707 and r = −0.484, P < 0.001 respectively), but not with IBS subtype. Expectations for IBS were “improved health”, “better information on causes and treatments” (94%) and “better disease recognition” (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients’ organization.ConclusionsFrench IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients’ organization

Randomised clinical trial: oesophageal radiofrequency energy delivery versus sham for PPI-refractory heartburn

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Endoscopic radiofrequency ablation or surveillance in patients with Barrett’s oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial

International audienceObjective Due to an annual progression rate of Barrett’s oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design. Design A prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity. Results 125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (p<0.001). At the same time, the prevalence LGD was 34.3% (95% CI 18.6 to 50.0) in the RFA group vs 58.1% (95% CI 40.7 to 75.4) in the surveillance group (OR=0.38 (95% CI 0.14 to 1.02), p=0.05). Neoplastic progression was found in 12.5% (RFA) vs 26.2% (surveillance; p=0.15). The complication rate was maximal after the first RFA treatment (16.9%). Conclusion RFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD. Trial registration number NCT01360541

Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.

International audienceBACKGROUND: Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication. METHODS: In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and ClinicalTrials.gov (NCT00542152). FINDINGS: 115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI -7 to 19; p=0*52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events. INTERPRETATION: Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience. FUNDING: Association François Aupetit, Société Nationale Française de Gastroentérologie, and the International Organization for the study of Inflammatory Bowel Disease