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Background. Crohn’s disease (CD) activity index (CDAI) is still widely used for monitoring clinical activity in CD patients, but is of little value as indicator of persistent inflammation in symptomless patients. Fecal calprotectin levels ≥150 μg/g are strongly indicative of endoscopically and/or histologically active disease. Our aim was to study, in a large cohort of CD patients, the relationship between CDAI and fecal calprotectin levels. Methods. CDAI and fecal calprotectin levels were evaluated in consecutive patients from a CD outpatient clinic. Results. We enrolled 193 CD patients, of whom 38% with CDAI 120, we found a high diagnostic accuracy of 72%, with 88% specificity and 50% sensitivity (positive predictive value: 76%, negative predictive value: 71%) to identify a calprotectin value ≥150 μg/g. Conclusion. CDAI scores between 100 and 150 display an acceptable ability to quantify the risk of persistent inflammation as expressed by the high calprotectin level.

Fisiopatologia della litiasi biliare

Fisiopatologia, quadri clinici e trattamento della calcolosi della via biliare principale

Fisiopatologia e quadri clinici delle complicanze della litiasi biliare

Extrahepatic cholangiocarcinomas (E-CCAs), are hepatobiliary cancers with features of cholangiocyte differentiations, originating from extrahepatic biliary tree at the bifurcation of the hepatic ducts and also in the distal duct. E-CCAs represent the most common type of cholangiocarcinomas (CCAs) and are characterized by poor overall survival. The principal risk factors for E-CCAs are strictly related to geographic location. Jaundice is the most common physical sign at disease presentation. Other common more non-specific symptoms include hepatomegaly, right upper qudrant mass, weight loss, vomiting, nausea, diarrhoea, malaise and fatigue. Unlike intrahepatic CCA, an incidental asymptomatic presentation occurs in a small percentage of cases. This chapter evaluates the principal clinical features of E-CCAs, briefly discussing its specific risk factors.

Background: Among patients with limited ulcerative colitis (UC), 30% ultimately extend to pancolitis and are at increased risk of adverse clinical outcomes. Risk of endoscopic extension has been found to correlate with clinical features such as early age of onset. Aims: We sought to determine whether histologic features correlate with disease extension. Methods: The study population consisted of 40 patients with UC from two large academic centers diagnosed between 2006 and 2017. Eligible cases had a diagnosis of endoscopically limited UC (Montreal E1 or E2) at baseline and ≥ 2 subsequent endoscopic examinations with biopsies. Severity of inflammation was scored using both the Mount Sinai Activity Index and Nancy Histological Index. Results: Patients were divided into two cohorts: those who progressed to pancolitis (Montreal E3) were defined as “Extenders” (n = 21), whereas “Non-extenders” (n = 19) were cases without progression in the follow-up period. The median follow-up time was 58.4months. The histologic scores in the endoscopically involved mucosa of the index biopsies were not associated with subsequent extension of disease, overall. However, among extender cohort, the index histology scores correlated with biopsy scores at extension (r = 0.455, P = 0.044) and index severity was associated with a shorter time to extension (r = − 0.611, P = 0.003). Furthermore, female patients had a shorter time to extension (P = 0.013). Conclusions: Histological severity of limited UC is not an independent predictor of extension in UC. However, among patients who subsequently extend, severe inflammation at baseline correlates with shorter progression time and severe inflammation when extension occurs. Patients with limited UC but severe histologic inflammation may warrant more frequent endoscopic surveillance.

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Background. Competitive sport has the potential for high levels of stress and anxiety that may affect performance and increase the risk of injuries. While benefits of pre-training assumption of N-3 polyunsaturated fatty acids are well known, poor data are available on Schisandra chinensis. Schisandra chinensis is a medicinal plant in use in Chinese medicine which increases physical working capacity and affords a stress protective effect. Objectives. We tested, in an open pilot study, the effect on competition related stress, anxiety and self-confidence of a novel formulation containing: PUFAs, Schisandra chinensis extract and vitamin D3. Methods. A novel formulation containing N-3 polyunsaturated fatty acids (PUFAs), Schisandra chinensis extract and vitamin D3, five ml per day was administered to one group of fifteen elite sport athletes (basketball players). Competitive State Anxiety Inventory-2 (CSAI-2) tests were administered at baseline and after 3 months. Results. All subjects completed the 3 months period of the study, all declaring a consumption >75% of daily recommended dose. No adverse event were registered. After intervention, the median cognitive state anxiety score remained mild (score 16) even if with an overall statistically significative decrease (p=0.005); same results were registered after intervention for the somatic state anxiety score (score 16) with an overall statistically significative decrease (p=0.008) and for the self-confidence score (score 22, range 15-30) with an overall statistically significative increase (p=0.008). Conclusion. The results showed the positive effect of the treatment on the control of stress and anxiety and the improvement of self-confidence in a large majority of the subject enrolled. However, further studies are needed to confirm our findings.

Background. Inflammatory bowel diseases (IBD) are associated with stress, poor quality of life, and attachment insecurity. Mentalization is the human ability to perceive and reason about feelings and psychological dispositions of one’s self and others. The chronic disorders are believed to affect patients’ mentalizing abilities and to determine a shift towards attachment insecurity in patients affected. In this study, the attachment dimensions and mentalization were assessed in IBD patients and healthy controls. Further knowledge about the interplay among IBD, mentalization, and attachment might shed more light into the psychopathological mechanisms leading to insecurity and vulnerability to stress in IBD. Methods. A group of 96 IBD patients and 102 healthy controls completed the attachment style questionnaire (ASQ), the reflective functioning questionnaire (RFQ), and the Eyes test, a performance-based measure of mentalization. Results. Compared to controls, IBD patients have shown more pronounced attachment anxiety and lower scores in the Eyes test. Disease activity was negatively correlated with the Eyes test scores. Conclusion. These findings have suggested a plausible impact of IBD on mentalization abilities and have provided new insights into the interplay between IBD, deficits in mentalization, and attachment insecurity. IBD patients are highly vulnerable to disease-related stress that may promote impairments in mentalization. Low mentalization might play a central role in the development of attachment insecurity and emotional disturbances in IBD. The present study’s results might open new scenarios for psychodynamic approaches to the treatment of the emotional disturbances in IBD based on attachment and mentalization theory.

Background: Simkania negevensis is an obligate intracellular Gram-negative bacterium (family Simkaniaceae, order Chlamydiales) that has been isolated from domestic and mains water supplies, is able to infect human macrophages, and can induce an inflammatory response in the host. Methods: From June to December 2016, in a single-center observational study, colonic Crohn’s disease patients and controls (subjects undergoing screening for colorectal cancer) underwent blood tests to identify serum-specific immunoglobulinG (IgG) and immunoglobulinA (IgA) to S.negevensis and a colonoscopy with biopsies for detection of S.negevensis DNA by polymerase chain reaction (PCR). Results: Forty-three Crohn’s disease patients and 18 controls were enrolled. Crohn’s disease patients had higher prevalence of IgA antibodies to S.negevensis compared with controls (20.9% versus 0%, p = 0.04). Simkaniaceae negevensis DNA was detected in 34.9% and 5.6% of intestinal biopsies in Crohn’s disease patients and controls, respectively (p = 0.02). All Crohn’s disease patients with PCR-positive biopsies for S.negevensis were IgG seropositive, with specific IgA in 60% of them (p < 0.001). Immunosuppressive therapies, extraintestinal manifestations, or disease activity did not influence the presence of S.negevensis in the Crohn’s disease population. Conclusions: We identified S.negevensis in Crohn’s disease patients by demonstrating the presence of S.negevensis mucosal DNA and seropositivity to the bacterium. These results could support the presence of an acute or persistent S.negevensis infection and suggest a possible role in the pathogenesis of Crohn’s disease.

Background Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes of intestinal inflammation and is thought to be related to an autoimmune reaction to genetic and environmental factors. Although evidence indicates that a polyphenolic-rich diet plays an important role in modulating aspects of chronic inflammation, few studies have focused on the effect of ellagitannin (ET)-rich food consumption on long-term remission maintenance in IBD patients with a high risk of clinical relapse. Therefore, we hypothesize that supplementation with a pomegranate juice, a naturally rich source of ETs, could significantly modulate the markers of mucosal and systemic inflammation relative to a control group receiving a placebo. Methods/design This double-blind, randomized controlled trial includes patients with IBD involving the colorectum who have been in stable therapy for at least the three previous months and have a high risk of clinical relapse. Participants are randomly allocated to one of two groups: active supplementation (125 mL of cv. Wonderful pomegranate juice) or placebo (125 mL) taken twice daily for 12 weeks. The primary outcome is changes in the fecal neutrophil-derived protein calprotectin, a surrogate marker of mucosal improvement, between the two groups from baseline to 12 weeks later. The secondary outcomes include transcriptomic changes in peripheral blood mononuclear cells and intestinal biopsies and changes in circulating inflammatory markers and trimethylamine-N-oxide levels. Pomegranate ET-derived metabolites are identified and quantified in plasma and urine samples. Discussion The results will provide information on the possible reduction of fecal calprotectin levels following the consumption of pomegranate juice. The findings will also show the in vivo metabolism of pomegranate ETs. Finally, the effect of 12-week pomegranate juice consumption on local and systemic inflammatory markers will be elucidated, which will likely provide additional insights into the maintenance of remission in IBD patients. Trial registration ClinicalTrials.gov, NCT03000101. Registered on 21 December 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3321-8) contains supplementary material, which is available to authorized users.

Summary Background Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non-invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies. Aim To review non-invasive diagnostic parameters and tools for NAFLD diagnosis and to formulate a diagnostic and prognostic algorithm for a better classification of patients. Methods A literature search was carried out on MEDLINE, EMBASE, Web of Science and Scopus for articles and abstracts in English. The search terms used included ‘NAFLD’, ‘non invasive method and NAFLD’, ‘transient elastography’ and ‘liver fibrosis’. The articles cited were selected based on their relevancy to the objective of the review. Results Ultrasonography still represents the first-line diagnostic tool for simple liver steatosis; its sensitivity could be enhanced by the complex biochemical score SteatoTest. Serum cytokeratin-18 is a promising and accurate non-invasive parameter (AUROCs: 0.83; 0.91) for the diagnosis of non-alcoholic steatohepatitis (NASH). The staging of liver fibrosis still represents the most important prognostic problem: the most accurate estimating methods are FibroMeter, FIB-4, NAFLD fibrosis score (AUROCs: 0.94; 0.86; 0.82) and transient elastography (AUROC: 0.84–1.00). Conclusions Different non-invasive parameters are available for the accurate diagnosis and prognostic stratification of non-alcoholic fatty liver disease which, if employed in a sequential algorithm, may lead to a reduced use of invasive methods, i.e. liver biopsy.

The role of general practitioners (GPs) and family paediatricians (FPs) in nutrition education and counselling for the general population is crucial. However, time constraints, insufficient knowledge and lack of suitable educational instruments have so far prevented family doctors from having an active role in this respect. In this paper the project “Osservatorio Nutrizionale Grana Padano (ON-GP)”, launched in 2005, an innovative and powerful tool for nutritional education and epidemiological monitoring by GPs and FPs, is described. GPs and FPs agreed to participate on a voluntary basis and were from all Italian regions. So far, since 2005, over 17,250 subjects (6306 children and 10,944 adults) have been surveyed by 346 GPs and 207 paediatricians. In addition to the possibility of free use of the software for clinical and educational purposes, GPs and FPs are also invited to take part in epidemiological research in order to build a nationwide database. The results of the survey are disseminated on an annual basis to family doctors and as a press release to the media, together with messages of nutrition education targeted to the general population. The success of the project so far — beyond all expectations — has prompted the planning of further improvements.

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Background & Aims The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests. Methods We measured SS and LS in 100 consecutive patients with hepatitis C virus–induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS–spleen diameter to platelet ratio score and platelet count to spleen diameter. Results SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values ( R 2 = 0.85). The results were internally validated using bootstrap analysis. Conclusions Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus–induced cirrhosis.

The gut flora carries out important functions for human health, although most of them are still unknown, and an alteration of any of them, due to a condition of dysbiosis, can lead to relevant pathological implications. Commensal bacteria in the gut are essential for the preservation of the integrity of the mucosal barrier function and an alteration in the anatomic functional integrity of this barrier has been implicated in the pathophysiologic process of different diseases. The gut microflora plays a role in modulating the intestinal immune system; in fact, it is essential for the maturation of gut-associated lymphatic tissue, the secretion of IgA and the production of antimicrobial peptides. The enteric flora represents a potent bioreactor which controls several metabolic functions, even if most of them are still unknown. The main metabolic functions are represented by the fermentation of indigestible food substances into simple sugars, absorbable nutrients, and short-chain fatty acids. Furthermore, the gut microbiota exerts important trophic and developmental functions on the intestinal mucosa. This overview focuses briefly on the physiological role of the gut microbiota in maintaining a healthy state and the potential role played by disturbances of both the function and composition of the gut microbiota in determining important pathological conditions, such as irritable bowel syndrome, inflammatory bowel disease, metabolic syndrome, obesity, and cancer.

Background and Aims: The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population-based cohort study. Methods: A total of 11 229 subjects (6610 men, 4619 women, age-range: 29–69 years, mean age: 48 years) were studied. At ultrasonography, GS were present in 856 subjects (338 men, 455 women) (7.1%). GS were followed by means of a questionnaire inquiring about the characteristics of specific biliary symptoms. Results: At enrolment, 580 (73.1%) patients were asymptomatic, 94 (11.8%) had mild symptoms and 119 (15.1%) had severe symptoms. GS patients were followed up for a mean period of 8.7 years; 63 subjects (7.3%) were lost to follow up. At the end of the follow up, of the asymptomatic subjects, 453 (78.1%) remained asymptomatic; 61 (10.5%) developed mild symptoms and 66 (11.4%) developed severe symptoms. In subjects with mild symptoms, the symptoms disappeared in 55 (58.5%), became severe in 23 (24.5%), remained stable in 16 (17%); in subjects with severe symptoms, the symptoms disappeared in 62 (52.1%), became mild in 20 (16.8%) and remained stable in 37 (31.1%). A total of 189 cholecystectomies were performed: 41.3% on asymptomatic patients, 17.4% on patients with mild symptoms and 41.3% on patients with severe symptoms. Conclusions: This study indicates that: (i) asymptomatic and symptomatic GS patients have a benign natural history; (ii) the majority of GS patients with severe or mild symptoms will no longer experience biliary pain; and (iii) a significant proportion of cholecystectomies are performed in asymptomatic patients. Expectant management still represents a valid therapeutic approach in the majority of patients.