Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

The kiwi fruit peptide kissper displays anti-inflammatory and anti-oxidant effects in in-vitro and ex-vivo human intestinal models.

Literature reports describe kiwi fruit as a food with significant effects on human health, including anti-oxidant and anti-inflammatory activity. Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells. The objective of this study was to investigate the kissper influence on intestinal inflammation using cultured cells and ex-vivo tissues from healthy subjects and Crohn's disease (CD) patients. The anti-oxidant and anti-inflammatory properties of kissper were tested on Caco-2 cells and on the colonic mucosa from 23 patients with CD, by challenging with the lipopolysaccharide from Escherichia coli (EC-LPS) and monitoring the appropriate markers by Western blot and immunofluorescence. EC-LPS challenge determined an increase in the intracellular concentration of calcium and reactive oxygen species (ROS). The peptide kissper was highly effective in preventing the increase of LPS-induced ROS levels in both the Caco-2 cells and CD colonic mucosa. Moreover, it controls the calcium increase, p65-nuclear factor (NF)-kB induction and transglutaminase 2 (TG2) activation inflammatory response in Caco-2 cells and CD colonic mucosa. Kissper efficiently counteracts the oxidative stress and inflammatory response in valuable model systems consisting of intestinal cells and CD colonic mucosa. This study reports the first evidence supporting a possible correlation between some beneficial effects of kiwi fruit and a specific protein molecule rather than generic nutrients.

Colonic gas transit in patients with bloating: the effect of an electromechanical stimulator of the abdominal wall.

BACKGROUND: The aim of our study was to evaluate gas retention, abdominal symptoms and changes in girth circumference in females with bloating using an active or sham abdominal wall mechanical stimulation. METHODS: In 14 female patients, complaining of bloating (11 with irritable bowel syndrome and 3 with functional bloating according to the Rome III criteria) a gas mixture was continuously infused into the colon for 1 h (accommodation period). Abdominal perception and girth were measured. At the beginning of the 30-min period of free rectal gas evacuation (clearance period), an electromechanical device was positioned on the abdominal wall of all patients. The patients were randomly assigned to an active or a sham stimulation protocol group. Gas retention, perception and abdominal distension were measured at the end of the clearance period. RESULTS: All patients tolerated the volume (1,440 ml) of gas infused into the colon. Abdominal perception and girth measurements was similar in both groups during the accommodation period. At the end of the clearance, the perception score and the girth changes in the active and sham stimulation groups were similar (2.8 ± 2.0 vs. 1.4 ± 1.2, p = 0.2 and 4.9 ± 4.5 vs. 2.8 ± 2.3 mm, p = 0.3 active vs. sham, respectively). Furthermore, the mechanical stimulation of the abdominal wall did not significantly reduce gas retention (495 ± 101 ml vs. 566 ± 55, active vs. sham, p = 0.1). CONCLUSIONS: An external mechanical massage of the abdominal wall did not improve intestinal gas transit, abdominal perception and abdominal distension in our female patients complaining of functional bloating.

[Morpho-functional evaluation of the small intestine patients with Crohn disease. Enema of the small intestine versus post-heparin plasma diamine oxidase]. / Valutazione morfo-funzionale dell'intestino tenue nei portatori di morbo di Crohn. Clisma del tenue versus DAO plasmatica post-eparinica.

Our study was directed not only towards the diagnosis of small bowel Crohn's disease, but especially to a quantitative analysis, for a correct therapeutical approach. This experimental trial is based on the relationship between radiological evidence, measured during small bowel enema, and the seriousness of the morphological and functional damage to the intestinal mucosal membrane, evaluated with a post-heparin diamine-oxidase activity test. With this method we studied 35 selected patients; 16 of them were affected by the disease with an exclusive localization in the small bowel and 5 have been considered separately, because 3 patients had already been operated and the other 2 showed different localizations. In our results, the two parameters were not constantly related to each other. In other words the enema's morphological data sometimes do not accord with the mucosal membrane integrity index expressed by the enzyme. Anyway the importance of this study is the attempt of making an objective comparison between an anatomic situation and its functional consequence. These aspects have a great significance in Crohn's disease.