Intestinal histomorphological and molecular alterations in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Changes in gut microbiota composition, enteric inflammation, impairments of the intestinal epithelial barrier and neuroplastic changes in the enteric nervous system have been reported in Parkinson's disease (PD) patients and could contribute to the onset of both neurological and gastrointestinal symptoms. However, their mutual interplay has rarely been investigated. This study evaluated, in an integrated manner, changes in faecal microbiota composition, morphofunctional alterations of colonic mucosal barrier and changes of inflammatory markers in blood and stools of PD patients. METHODS: Nineteen PD patients and nineteen asymptomatic subjects were enrolled. Blood lipopolysaccharide binding protein (LBP, marker of altered intestinal permeability) and interleukin-1ß (IL-1ß) levels, as well as stool IL-1ß and tumour necrosis factor (TNF) levels, were evaluated. Gut microbiota analysis was performed. Epithelial mucins, collagen fibres, claudin-1 and S100-positive glial cells as markers of an impairment of the intestinal barrier, mucosal remodelling and enteric glial activation were evaluated on colonic mucosal specimens collected during colonoscopy. RESULTS: Faecal microbiota analysis revealed a significant difference in the α-diversity in PD patients compared to controls, while no differences were found in the ß-diversity. Compared to controls, PD patients showed significant chenags in plasma LBP levels, as well as faecal TNF and IL-1ß levels. The histological analysis showed a decrease in epithelial neutral mucins and claudin-1 expression and an increased expression of acidic mucins, collagen fibres and S100-positive glial cells. CONCLUSIONS: Parkinson's disease patients are characterized by enteric inflammation and increased intestinal epithelial barrier permeability, as well as colonic mucosal barrier remodelling, associated with changes in gut microbiota composition.

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation.

Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.

Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients.

AIMS: Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission. METHODS: We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression. RESULTS: Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission. CONCLUSION: In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.

Corticosteroid Treatment at Diagnosis: An Analysis of Relapses, Disease Extension, and Colectomy Rate in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis is a chronic relapsing disease usually treated with mesalamine. The need of steroid therapy at diagnosis is generally considered as a poor prognostic factor. AIMS: The aim of our study was to assess whether patients treated with corticosteroids at diagnosis have more clinical relapses, disease progression, or an increased risk of colectomy during a 5-year follow-up. METHODS: We retrospectively evaluated patients who had received diagnosis of ulcerative colitis with a 5-year follow-up. Relapse was defined as a worsening of symptoms requiring an increase in medical treatment. Progression of disease was defined as a proximal extension of mucosal involvement, comparing the colonoscopy performed 5 years after diagnosis with the first one. The need of corticosteroid treatment at diagnosis was correlated to number of relapses, disease progression, and colectomy rate. RESULTS: We included 230 patients, 116 of them (50%) treated with steroids at diagnosis. Multivariate analysis demonstrated that there is a strong correlation between corticosteroid use and number of relapses (p < 0.01), as well as with disease progression (p < 0.05). Seventeen patients (7.4%) underwent colectomy, but the correlation with steroids was not statistically significant. CONCLUSIONS: These data provide evidence that the need of corticosteroids at diagnosis is associated with a worse clinical outcome.

The complex interplay between gastrointestinal and psychiatric symptoms in irritable bowel syndrome: A longitudinal assessment.

AIMS: The aims of this study were to better define the relationship between irritable bowel syndrome (IBS) and psychiatric disorders and to examine the efficacy of paroxetine in the treatment of IBS patients. METHODS: One hundred fifty subjects with diagnosis of IBS (Roma III criteria) and relative sub-classification (constipated, diarrhea, and mixed) were assessed for psychopathological features and gastrointestinal symptoms using IBS Symptom Severity Score and were consecutively enrolled. Fifty patients assumed paroxetine for 16 weeks and were longitudinally evaluated. RESULTS: The entire sample had a moderate/severe gastrointestinal symptomatology (IBS-SSS 285.1 ± 98.6). The IBS subtypes were diarrhea (47.3%), constipated (32%), and mixed (20.7%). Panic disorder was found in 17.4% and major depressive episode in 14.7%. More than 50% of the patients showed "psychopathological features." This group showed more severe gastrointestinal symptoms and worse quality of life than the group without any psychiatric comorbidity (44%). Psychiatric patients also showed a significant impairment of physical state, subjective feeling of well-being, and leisure activities when compared with no psychiatric patients. When the IBS-SSS > 300 group was subgrouped in psychiatric (67.2%) and no psychiatric (32.8%), we found significant differences in all clinician-administered and self-reported scales with more severe psychopathological features in psychiatric group (P < 0.01). Among the patients treated with paroxetine, 34 (68%) completed the longitudinal evaluation showing a significant improvement of both psychiatric and gastrointestinal symptoms. CONCLUSIONS: This study confirms a high presence of psychiatric comorbidities, emphasizing the need for psychiatric screening in all patients with IBS; moreover, the longitudinal evaluation of patients treated with paroxetine showed a significant improvement of both psychiatric and gastrointestinal symptoms.

Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome.

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

OBJECTIVES: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. METHODS: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. RESULTS: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). CONCLUSIONS: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

BACKGROUND & AIMS: Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS: In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS: FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS: Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Specific probiotics and prebiotics to improve the quality of life of patients with chronic irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder with an important impact on patients' quality of life. Although several data indicate that psychological symptoms are frequently reported by patients with IBS, few therapies have been evaluated regarding these issues. METHODS: A retrospective observational study was conducted to evaluate the effectiveness of a probiotic-based dietary supplement (Colicron®) in a group of patients with diarrhea-predominant IBS (IBS-D). We included patients treated with Colicron® (1 cps/day for 8 weeks). Primary endpoint was the gastrointestinal symptoms' remission evaluated by Visual Analogue Scale (VAS); secondary endpoint was the impact of the treatment on physical and mental health evaluated by Hospital Anxiety and Depression Score (HADS) and Short Form Health Survey 36 (SF-36). VAS was assessed at week 4 (T4), week 8 (T8) and week 12 (T12), whereas HADS and SF-36 were performed even at the start of the Colicron® treatment (T0). RESULTS: An improvement of VAS Score was observed at T8 (P<0.001) and T12 (P<0.05) compared to T4. Lower HADS-A (anxiety subdomain) score was obtained at each time point versus T0 (P<0.01), and higher scores of all SF-36 domains were observed during the treatment (0.05

Expression of Circulating let-7e and miR-126 May Predict Clinical Remission in Patients With Crohn's Disease Treated With Anti-TNF-α Biologics.

BACKGROUND: The identification of new biomarkers predictive of response to antitumor necrosis factor alpha (anti-TNF-α) monoclonal antibodies remains an unmet medical need in Crohn's disease (CD) because a high percentage of patients show no clinical improvement after treatment or can lose response over time. MicroRNAs (miRNAs) can regulate inflammatory and immunological responses and were found to play a role in CD. METHODS: Baseline serum samples from 37 CD patients previously treated with infliximab or adalimumab, as per clinical practice, were obtained from the serum library at the Gastroenterology Unit of the University Hospital of Pisa, Italy. Patients were categorized as responders or nonresponders based on the following treatment outcomes: clinical remission at weeks 14 and 54 and endoscopic remission at week 54. The expression levels of a panel of selected miRNAs were analyzed by real-time polymerase chain reaction. Comparisons of miRNA expression between responders and nonresponders and statistical analyses were performed by MedCalc and GraphPad Prism software. Receiver operating characteristic curve analyses were calculated to evaluate the predictive performance of potential biomarkers. RESULTS: Patients in clinical remission at week 14 had a lower let-7e expression, whereas those in clinical remission at week 54 had lower levels of circulating miR-126 than nonresponders. The receiver operating characteristic curve analysis identified optimal cutoff values with assay sensitivity and specificity of 92.9% and 61.1%, for let-7e, and 62.5% and 83.3%, for miR-126, respectively. CONCLUSION: These results provide evidence that expression levels of circulating let-7e and miR-126 at baseline may predict clinical remission in CD patients treated with anti-TNF-α biologics.

We found that the baseline expression of 2 microRNAs (Let-7e and miR126) involved in inflammation and immune system regulation may predict short- and long-term clinical remission in CD patients treated with anti-TNF-α biologics, supporting clinicians in therapeutic decision-making.

Therapeutic Drug Monitoring as a Tool for the Clinical Outcome Prediction in Vedolizumab-Treated Patients: An Italian Pilot Study.

Over the years, vedolizumab (VDZ) has emerged as a more effective target therapy for inflammatory bowel disease. The aim of this work was to analyze a cohort of inflammatory bowel disease patients, evaluating the association between VDZ serum concentrations at 6 months from starting therapy and their clinical and biochemical indexes within one year of treatment, correlating drug levels with response and clinical remission. Forty patients treated with VDZ were enrolled. Drug concentrations were quantified through ELISA methods. VDZ levels correlated with hemoglobin levels at twelve months of therapy (p = 0.03) and with clinical remission at twelve months of therapy (p = 0.03); patients who reached clinical remission showed higher VDZ concentrations. A VDZ cut-off value of 43.1 µg/mL was suggested, predicting clinical remission at twelve months of therapy. A statistically significant association between VDZ levels at T6 and calprotectin <250 µg/g at T12 was found (p = 0.04). Furthermore, the optimal threshold value of VDZ levels at T6 associated with calprotectin <250 µg/g at T12 was identified: through levels higher than 45.2 µg/mL, we were able to predict remission one year after therapy. In the final regression multivariate model, no factor was retained as a predictor of clinical remission at one year of treatment. In conclusion, this is the first pilot study reporting a possible VDZ serum cut-off value able to predict not only the clinical remission at twelve months of therapy but also the calprotectin level, which is very important, as it is a surrogate marker of mucosal healing.

Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn's Disease: A Prospective Pilot Study.

BACKGROUND: No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST. METHODS: We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing. RESULTS: Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001). CONCLUSIONS: This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions.

This prospective pilot study showed that the assessment of IL-23 levels at baseline could predict clinical and endoscopic outcomes to ustekinumab therapy in Crohn's disease. Testing this biomarker before starting a biological therapy could be useful for a personalized choice.

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Management of inflammatory bowel disease in the elderly: A review.

The burden of Inflammatory Bowel Disease (IBD) is increasing worldwide, with a particular increase in the prevalence in the elderly population, due to the ageing of young-onset IBD as well as to the increasing incidence in elderly patients. Elderly IBD patients present specific challenges to the treating physician, as they have comorbidities, lower functional reserves, and higher risk of treatment-related complications. The diagnosis of IBD in the elderly may be difficult due to a more subtle disease presentation and to a wide range of differential diagnosis. Moreover, as these patients are often excluded from clinical trials, there is a lack of high-quality evidence to inform on the most appropriate management. Despite an increasing prevalence, the management of IBD in the elderly is still hindered by frequent misconceptions by physicians treating these patients. Due to a erroneous notion of a milder disease course and fear of adverse events, elderly IBD-patients are managed with frequent and continuous use of steroids and undertreated with effective medical therapies. In this review, we describe the principles of management of IBD in the elderly, which is a topic of increasing importance to IBD clinics, that will have to progressively adapt to care for an ageing population.

Potential missed diagnoses of Crohn's disease in tertiary care: impact on drug utilization and healthcare facilities use.

BACKGROUND: A missed diagnosis of Crohn's disease (CD) can delay treatment initiation with consequences on disease course. AIMS: To measure the possible impact of missed diagnoses on drug utilization and access to healthcare facilities in a real-world cohort of CD patients. METHODS: This retrospective observational study has been conducted on the regional administrative databases of Tuscany (Italy). We included patients with a first record of CD diagnosis between 06/11/2011 and 06/30/2016. Possible missed diagnosis (exposure) was defined by hospital presentation for gastrointestinal symptoms consistent with CD diagnosis that occurred in the 7-60 months preceding CD diagnosis. We compared exposed and non-exposed patients by assessing time-free from biologic drugs and from Emergency Department (ED) or hospital access. Hazard ratio (HR) was calculated using Cox models. RESULTS: Among 3342 CD patients, 584 (17.5%) had a possible missed diagnosis. A risk of being treated with biologic drugs [adjusted HR (aHR): 2.17, 95% CI: 1.75-2.71] and of access to ED or hospitalization (aHR: 1.59, 95% CI: 1.44-1.75) was observed in patients with a possible missed diagnosis as compared to those without. CONCLUSION: Tertiary care caregivers should be trained in the identification of early CD symptoms, to timely identify CD diagnosis and optimize pharmacological treatment and disease management.

Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review.

BACKGROUND: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.

Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn's Disease.

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

Treatment and Management of Chronic Inflammatory Bowel Diseases: Optimizing Present and Future Therapeutic Choices.

Inflammatory bowel diseases (IBD) are chronic relapsing diseases of the gastrointestinal tract of unknown origin, resulting from an aberrant immune response to microbial and gut-specific antigens in genetically susceptible patients [...].

Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicentre Case Series.

BACKGROUND: Hereditary colorectal cancer syndromes [HCCS] are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer [CRC]. Coexisting inflammatory bowel disease [IBD], including ulcerative colitis [UC] and Crohn's disease [CD], with HCCS is exceedingly rare and presumably increases the risk of early-onset CRC. METHODS: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS: This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified [IBD-U]) and concomitant HCCS. Among these 26 patients([median age 33 years, interquartile range [IQR] 20-44], 15 [57.7%] were males, 24 [92.3%] Caucasians, and two [7.7%] of Arab origin. HCCS was diagnosed before the IBD diagnosis in 11 patients [42.3%], after diagnosis of IBD in 11 patients [42.3%], and concurrently in four patients [15.4%]. Sixteen patients had Lynch syndrome, seven had familial adenomatous polyposis [FAP], two had MYH-associated polyposis [MAP], and one had attenuated FAP [AFAP]. The most frequent genetic mutations were those of APC [n = 7] and MLH1 [n = 7]. Overall, CRC developed in 38.5% of patients [n = 10]: in four patients [40%] after IBD diagnosis, in four [40%] patients before IBD diagnosis, and in two patients the two conditions were diagnosed simultaneously. Eighteen [69.2%] patients underwent colectomy or abdominal surgery: nine patients due to CRC diagnosis, five patients preventively due to the underlying HCCS, three due to the underlying HCCS and concomitant active IBD disease, and one patient because of active IBD disease. One patient died due to CRC. CONCLUSIONS: To date, this is the largest case series of patients with IBD and HCCS. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort, despite the endoscopic surveillance. The optimal medical approach still needs to be addressed.