Measuring disease activity in Crohn's disease

In the last few years the management of Crohn's disease (CD) has changed due to the introduction of new therapeutic agents that provide more alternative options in patients with severe diseases, introducing new concepts regarding treatment timing. At the moment, the absence of good predictors of disease outcome and a subclinical marker available to predict relapse during clinical remission are major problems in the management of CD. In recent decades, the evaluation of several variables has been proposed to address this issue, including disease behavior, clinical-endoscopic activity and intestinal damage. In particular, definition of mucosal restitution or healing after therapy has been proposed as a surrogate of efficacy and new goal of the therapy. Regarding this concept, several criticisms have been raised, such as the need to better define the role of mucosal healing in a transmural disease. In order to address this issue, new alternative techniques providing both extraluminal and luminal intestinal damage have been proposed, including ultrasonography, computed tomography and magnetic resonance imaging. © 2012 Springer Science+Business Media, LLC

Tumor infiltrating regulatory t cells in sporadic and colitis-associated colorectal cancer: The red little riding hood and the wolf

Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity

Severity of postoperative recurrence in Crohn's disease: Correlation between endoscopic and sonographic findings

Background: Crohn's disease (CD) recurrence is currently assessed by ileocolonoscopy. Small intestine contrast ultrasonography (SICUS) visualizes the small bowel lesions in CD, although its role after curative resection is undefined. We aimed to investigate the accuracy of SICUS in assessing CD recurrence after ileocolonic resection when using ileocolonoscopy as a gold standard. The correlation between the bowel wall thickness (BWT) measured by SICUS and the endoscopic score of recurrence was also assessed. Methods: The analysis included 72 CD patients with ileocolonic resection requiring ileocolonoscopy, undergoing SICUS within 6 months. Recurrence was assessed by ileocolonoscopy using the Rutgeerts' score. SICUS was performed after PEG ingestion and findings compatible with recurrence included: increased BWT (>3 mm), bowel dilation (>25 mm) or stricture (<10 mm). Results: Ileocolonoscopy detected recurrence in 67/72 (93%) patients. SICUS detected findings compatible with recurrence in 62/72 (86%) patients (5 false negative (FN), 4 false positive (FP), 1 true negative (TN), 62 true positive (TP)), showing a 92.5% sensitivity, 20% specificity, and 87.5% accuracy for detecting CD recurrence. The BWT detected by SICUS was correlated with the Rutgeerts' score (P = 0.0001; r = 0.67). The median BWT, the extent of the ileal lesions, and the prestenotic dilation were higher in patients with an endoscopic degree of recurrence ≥3 versus ≤2 (P < 0.001) and the lumen diameter was lower in patients with a Rutgeerts' score ≥3 versus ≤2 (P < 0.0001). Conclusions: Although SICUS and ileocolonoscopy provide different views of the small bowel, SICUS shows a significant correlation with the endoscopic findings. SICUS may represent an alternative noninvasive technique for assessing CD recurrence after ileocolonic resection. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc

Fractal Markets Hypothesis and the Global Financial Crisis: Scaling, Investment Horizons and Liquidity

We investigate whether fractal markets hypothesis and its focus on liquidity and invest- ment horizons give reasonable predictions about dynamics of the financial markets during the turbulences such as the Global Financial Crisis of late 2000s. Compared to the mainstream efficient markets hypothesis, fractal markets hypothesis considers financial markets as com- plex systems consisting of many heterogenous agents, which are distinguishable mainly with respect to their investment horizon. In the paper, several novel measures of trading activity at different investment horizons are introduced through scaling of variance of the underlying processes. On the three most liquid US indices - DJI, NASDAQ and S&P500 - we show that predictions of fractal markets hypothesis actually fit the observed behavior quite well.Comment: 11 pages, 3 figure

Investor behavior around targeted liquidity announcements

This is the author accepted manuscript.We exploit announcements related to targeted longer-term financing operations (TLTROs) as exogenous shocks in investor perceptions to test recent theories on bank funding liquidity (Liu 2015, Ahnert et al. 2019). We find that banks with high derivative holdings and more exposed to sovereign credit risk respond better to the announcements, consistent with the view that lower funding costs benefit banks with higher asset encumbrance and located in more vulnerable Eurozone countries. The TLTRO announcements also elicit reductions in short positions on bank stocks relative to stocks of non-financial corporations without impairing their market liquidity. Robustness tests rule out that our results are driven by confounding events and anticipation effects. Placebo tests confirm that the TLTRO announcements are driving the estimated price reactions and changes in short positions

Non-invasive techniques for assessing postoperative recurrence in Crohn's disease

Postoperative recurrence after ileo-colonic resection is a feature of Crohn's Disease (CD), almost 73% of patients show endoscopic recurrence at 1 year and 90% at 3 years. After surgical resection for CD, symptoms may be related to the surgical resection itself. Moreover, the development of an early severe endoscopic recurrence within 1 year represents a risk factor for early clinical recurrence. On the basis of these observations, the early detection and assessment of asymptomatic endoscopic recurrence may allow a timely and appropriate treatment of CD patients after ileo-colonic resection. At this purpose, conventional colonoscopy with ileoscopy currently represents the gold standard for assessing CD recurrence, graded according to the Rutgeerts' score. Lesions compatible with CD recurrence can be also detected by conventional radiology, including small bowel follow through and enema, both associated with a high radiation exposure. Due to the ineluctable course of CD after resection, and to the need of a proper follow up for assessing CD recurrence, several alternative, non invasive techniques have been searched in order to assess the post-operative recurrence, including: faecal alpha 1-antitrypsin clearance, faecal calprotectin, 99Tc-HMPAO scintigraphy, virtual colonoscopy, ultrasonography and, more recently, wireless capsule endoscopy (WCE) and Small Intestine Contrast Ultrasonography (SICUS). Among these, current evidences suggest that in experienced hands, ultrasound examination by SICUS represents a non-invasive technique useful for assessing recurrence in CD patients under regular follow up after surgery. The same findings are suggested for WCE, although the impact risk related to the recurrence or to the surgical anastomosis itself limits the use of this non-invasive technique for assessing CD recurrence after surgery. © 2008 Editrice Gastroenterologica Italiana S.r.l

Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis: Relationship with colonic metaplasia

Aim: To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. Methods: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn's disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identified by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated. Results: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. Conclusion: Present findings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA

Wireless capsule endoscopy and proximal small bowel lesions in Crohn's disease

AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detected proximal SB lesions in 16/32 (50%) patients (14 aphthoid ulcers, 2 deep ulcers, one stricture), which appeared not to be related to clinical parameters [epigastric pain, age, smoking, non-steroidal anti-inflammatory drugs (NSAIDs), IDA]. Among patients with proximal SB lesions, 6 (37%) were smokers, 3 (19%) NSAID users, 3 (19%) had epigastric pain and 4 (25%) had IDA. SICUS detected proximal SB lesions in 3/32 patients (19%) also showing lesions with WCE. No correlations were observed between proximal SB lesions assessed by WCE or by SICUS (χ2 = 1.5, P = 0.2). CONCLUSION: The use of WCE allows the detection of previously unknown upper SB lesions in a high proportion of patients with a previous diagnosis of CD involving the distal ileum. © 2010 Baishideng