Artificial Intelligence in the Diagnosis of Upper Gastrointestinal Diseases.

Artificial intelligence (AI) has enormous potential to support clinical routine workflows and therefore is gaining increasing popularity among medical professionals. In the field of gastroenterology, investigations on AI and computer-aided diagnosis (CAD) systems have mainly focused on the lower gastrointestinal (GI) tract. However, numerous CAD tools have been tested also in upper GI disorders showing encouraging results. The main application of AI in the upper GI tract is endoscopy; however, the need to analyze increasing loads of numerical and categorical data in short times has pushed researchers to investigate applications of AI systems in other upper GI settings, including gastroesophageal reflux disease, eosinophilic esophagitis, and motility disorders. AI and CAD systems will be increasingly incorporated into daily clinical practice in the coming years, thus at least basic notions will be soon required among physicians. For noninsiders, the working principles and potential of AI may be as fascinating as obscure. Accordingly, we reviewed systematic reviews, meta-analyses, randomized controlled trials, and original research articles regarding the performance of AI in the diagnosis of both malignant and benign esophageal and gastric diseases, also discussing essential characteristics of AI.

A "tailored" interventional and surgical management for moderate to critical acute pancreatitis in late phase: a cohort study.

PURPOSE: Several interventional procedures are available to treat moderate-to-critical acute pancreatitis (AP) in its late phase. The ongoing debate on these options, together with the scarcity of reported quality of life (QoL) information in the Literature, prompted us to conduct a review of our experience. METHODS: All the patients treated at our referral Center for moderate-to-critical AP according to Determinant-Based Classification (DBC) were retrospectively reviewed. Patients treated conservatively or operated within 4 weeks were excluded. The included patients were managed following a "tailored" interventional-surgical approach, which did not exclude the possibility to skip one or more steps of the classic "step-up" approach, based on the patient's clinical course, and divided into four groups, according to the first procedure performed: percutaneous drainage (PD), endoscopic approach (END), internal derivation (INT), and necrosectomy (NE). In-hospital and mid-term follow-up variables were analyzed. RESULTS: The study sample consisted in 47 patients: 11 patients were treated by PD, 11 by END, 13 by INT, and 12 by NE. A significant distribution of the DBC severity (p = 0.029) was registered among the four groups. Moreover, the NE group had statistically significant reduced SF-36 scores in the domain of social functioning at 3 months (p = 0.011), at 1 year (p = 0.002), and at 2 years (p = 0.001); role limitations due to physical health at 6 months (p = 0.027); and role limitations due to emotional problems at 1 year (p = 0.020). CONCLUSIONS: In the "late phase" of moderate to critical AP requiring an invasive management, PD, END, INT, and NE are all effective options, depending on patents' status and necrosis location. A "tailored" interventional-surgical management could be pursued, but up-front more invasive approaches are at higher risk of worse QoL. TRIAL REGISTRATION: The manuscript was registered at clinicaltrials.gov in 04/2021 and identified with NCT04870268.

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.

Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis: Comprehensive Appraisal With Off- and On PPI Impedance-pH Monitoring.

OBJECTIVES: Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. METHODS: Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). RESULTS: Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. DISCUSSION: Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

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.

Gastroesophageal reflux symptoms among Italian university students: epidemiology and dietary correlates using automatically recorded transactions.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. METHODS: A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. RESULTS: We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. DISCUSSION: The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. CONCLUSIONS: To our knowledge, this is the first study evaluating the prevalence of typical GERD-related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system.

Clinical outcomes with long-term sorafenib treatment of patients with hepatocellular carcinoma: a multicenter real-life study.

AIM: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients. METHODS: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months. RESULTS: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival. CONCLUSION: Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications.

Analyses of the Post-reflux Swallow-induced Peristaltic Wave Index and Nocturnal Baseline Impedance Parameters Increase the Diagnostic Yield of Impedance-pH Monitoring of Patients With Reflux Disease.

BACKGROUND & AIMS: Analyses of impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been proposed to increase the accuracy of diagnosis of reflux disease. We assessed whether these improve the diagnostic yield of impedance pH monitoring of reflux disease. METHODS: We performed a prospective study of consecutive patients with proton pump inhibitor-responsive heartburn who underwent 24-hour impedance pH monitoring at hospitals in Italy from January 2011 through December 2013. Reviewers blindly analyzed off-therapy impedance pH tracings from 289 patients with proton pump inhibitor-responsive heartburn, 68 with erosive reflux disease and 221 with non-erosive reflux disease (NERD), along with 50 healthy individuals (controls). The PSPW index, the MNBI, the esophageal acid exposure time, the number of total refluxes, and the bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). RESULTS: In receiver operating characteristic analysis, the area under curve of the PSPW index (0.977; 95% confidence interval, 0.961-0.993) was significantly greater than that of the other impedance pH parameters in identifying patients with reflux disease (P < .001). The PSPW index and the MNBI identified patients with erosive reflux disease with the highest level of sensitivity (100% and 91%, respectively), as well as the 118 pH-positive (99% and 86%) and 103 pH-negative (77% and 56%) cases of NERD. The PSPW index and the MNBI identified pH-negative NERD with the highest level of sensitivity; values were 82% and 52% for the 65 SAP-positive and/or SI-positive cases and 68% and 63% for the 38 SAP-negative and SI-negative cases. Diagnoses of NERD were confirmed by pH-only criteria, including those that were positive on the basis of the SAP or SI, for 165 of 221 cases (75%) and by impedance pH criteria for 216 of 221 cases (98%) (P = .001). CONCLUSIONS: The PSPW index and the MNBI increase the diagnostic yield of impedance pH monitoring of patients with reflux disease. Analysis of impedance pH data by calculating the PSPW index and the MNBI can increase the accuracy of diagnosis of patients with reflux disease, compared with pH-only data.

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.

Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11,326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

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.

Symptom patterns can distinguish diverticular disease from irritable bowel syndrome.

BACKGROUND: Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS. MATERIALS AND METHODS: Patients with DD or IBS, matched for age and gender (1/1) were consecutively recruited. Data on demographic parameters, voluptuary habits, inheritance of disease and symptoms were collected. Moreover, the association between pain > 24 h, and clinical parameters were evaluated. RESULTS: Ninety patients with DD and 90 patients with IBS (DD: F/M: 46/44; age: 50.9 years; IBS: 46/44; 50.4) were selected from an overall population of 1275 patients. Only nine patients with DD (10%) fulfilled the criteria for IBS diagnosis. Abdominal pain > 24 h was more prevalent in SDD than in patients with IBS (20 vs. 6 patients; P < 0.01). Furthermore, compared with IBS, patients with DD showed more episodes of pain > 24 h requiring medical attention (80% vs. 33%; P < 0.01). CONCLUSIONS: Abdominal pain lasting for more than 24 h discriminates patients with DD compared with those with IBS. Identifying this symptom could be an appropriate strategy to define the diagnosis and management.

Neuroendocrine markers and psychological features in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: The key role of the brain-gut axis in the pathophysiology of irritable bowel syndrome (IBS) has been recognized. The aim of this study was to assess the possible association between IBS, neuroendocrine markers, and psychological features. METHODS: One hundred and twenty-five consecutive IBS patients and 105 healthy subjects were enrolled. Plasma serotonin, plasma and urinary cortisol, and plasma neuropeptide Y levels were evaluated. All patients were given a questionnaire to assess IBS symptom severity. In 66 patients, a psychodiagnostic assessment was carried out. RESULTS: A high incidence of specific psychological features, including state anxiety (69.69 %), trait anxiety (54.54 %), obsessions and compulsions (28.78 %), was observed in IBS patients. A positive correlation between neuropeptide Y and state anxiety (r = 0.287, p = 0.024) and simulation/social ingenuity (r = 0.269, p = 0.039) was found in these patients. In diarrhea-predominant IBS, plasma cortisol was linearly related to plasma serotonin (r = 0.5663, p < 0.001). CONCLUSIONS: In IBS patients, a significant correlation was found between specific psychological features and neuroendocrine markers, especially plasma cortisol and neuropeptide Y; in diarrhea-predominant IBS, a correlation between plasma cortisol and serotonin was found, although it needs to be confirmed in more extensive cohorts.

Accuracy of b-GGT fraction for the diagnosis of non-alcoholic fatty liver disease.

BACKGROUND: Serum gamma-glutamyltransferase (GGT) activity is a sensitive but non-specific marker of non-alcoholic fatty liver disease (NAFLD). Recently, four GGT fractions (big-, medium-, small-, free-GGT) were described in humans. AIM: We aimed to investigate whether a specific GGT fraction pattern is associated with NAFLD. METHODS: Gamma-glutamyltransferase fractions were determined in patients with NAFLD (n = 90), and compared with those in control subjects (n = 70), and chronic hepatitis C (CHC, n = 45) age and gender matched. RESULTS: Total GGT was elevated in NAFLD as compared to controls (median, 25°-75° percentile: 39.4, 20.0-82.0 U/L vs. 18.4, 13.2-24.9 U/L respectively, P < 0.001). All fractions were higher in NAFLD than in controls (P < 0.001). The b-GGT showed the highest diagnostic accuracy for NAFLD diagnosis [area under ROC curve (ROC-AUC): 0.85; cut-off 2.6 U/L, sensitivity 74%, specificity 81%]. Also subjects with CHC showed increased GGT (41.5, 21.9-84.5 U/L, P < 0.001 vs. controls, P = n.s. vs. NAFLD), as well as m-, s-, and f-GGT, while b-GGT did not show any significant increase (P = n.s. vs. HS, P < 0.001 vs. NAFLD). In subjects with CHC, s-GGT showed the best diagnostic value (ROC-AUC: 0.853; cut-off 14.1 U/L, sensitivity 73%, specificity 90%). Serum GGT did not show any value in the differential diagnosis between NAFLD and CHC (ROC-AUC 0.507, P = n.s.), while b-GGT/s-GGT ratio showed the highest diagnostic accuracy for distinguishing NAFLD and CHC (ROC-AUC: 0.93; cut-off value 0.16, sensitivity 82%, specificity 90%). CONCLUSIONS: b-GGT increases in NAFLD, but not in CHC. GGT fraction analysis might help in improving the sensitivity and specificity of the diagnosis of NAFLD and other liver dysfunctions.

Clinical features of symptomatic uncomplicated diverticular disease: a multicenter Italian survey.

PURPOSE: Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease. METHODS: This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria. RESULTS: A total of 598 patients (50 % female, age 69 years), 71 % with newly diagnosed symptomatic uncomplicated diverticular disease and 29 % with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78 % of the patients. Recurrent short-lived abdominal pain (<24 h) was present in 70 % (relieved by evacuation in 73 %), prolonged abdominal pain (>24 h) in 27 %, and recurrent abdominal bloating in 61 % of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13 % of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7 % of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain. CONCLUSIONS: Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.

Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis.

OBJECTIVE: No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients. DESIGN: Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+). RESULTS: Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients. CONCLUSION: Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.

Eosinophilic esophagitis: novel concepts regarding pathogenesis and clinical manifestations.

Eosinophilic esophagitis is a chronic disease whose incidence and prevalence are increasing, based on a genetic-driven interaction between environment and immune system. Several gene loci involved in the development of the disease have been identified. A two-step mechanism has been hypothesized: a thymic stromal lymphopoietin-induced allergic sensitization followed by upregulation of CAPN14-related esophageal-specific pathways. Environment seems to have a larger effect than genetic variants. Factors that could play a role are allergens, drugs, colonizing bacteria and possibly Helicobacter Pylori infection. Acting on these modifiable risk factors may be a tool to prevent the disease. EoE is characterized by a typical eosinophilic infiltrate limited to the esophageal epithelium, supported by a Th2-mediated immune response, found in other atopic conditions. The key of the pathogenesis is the disfunction of the epithelial barrier which allow the interaction between allergens and inflammatory cells. Eosinophilic-predominant inflammation leads to the typical wall remodeling, histologically characterized by epithelial and smooth muscle hyperplasia, lamina propria fibrosis and neo-angiogenesis. These alterations find their clinical expression in the pattern of symptoms: dysphagia, food impaction, chest pain, heartburn.

Therapeutic drug monitoring in Crohn's disease patients treated with anti-TNF: a comparison of two techniques.

BACKGROUND: Therapeutic drug monitoring is a useful clinical decision aid in managing patients with inflammatory bowel disease treated with anti-tumor necrosis factor (anti-TNF). Various techniques are available to evaluate drug trough levels, and among these a point-of-care (POC) method has been proposed to overcome the limitations inherent to other methodologies. In this study we aimed to evaluate the capability of POC to discriminate between relapse and remission disease phases, and to assess the concordance of the POC and homogeneous mobility shift assay (HMSA) results. METHODS: Drug trough level of 46 Crohn's disease patients treated with either adalimumab or infliximab were evaluated with both a POC technique and an HMSA at various time points (week-16 and -48) during anti-TNF treatment. RESULTS: Median adalimumab trough level of patients in remission were significantly higher as compared to relapsing patients using both HMSA (week 16, P = 0.0001; week48, P = 0.001) and POC (week 16, P = 0.0003; week 48, P = 0.0012), and similar results were observed with infliximab trough level at week 16 (HMSA, P = 0.019; POC, P = 0.0072). Overall, we observed a good correlation between the techniques for both infliximab (r = 0.76; P < 0.0001) and adalimumab (r = 0.75; P < 0.0001), with no difference in discriminatory accuracy between assays (infliximab: HMSA versus POC c-index, 0.921 versus 0.895, P =0.149; adalimumab: HMSA versus POC c-index, 0.817 versus 0.850, P = 0.197). CONCLUSION: Both POC and HMSA assays are able to reliably differentiate relapse and remission phases in Crohn's disease patients treated with anti-TNF. These techniques showed good concordance and we feel that their preferential use should be based on local accessibility, physicians' experience and preference, and the need for timeliness availability of results.