Sonography of the small bowel after oral administration of fluid: an assessment of the diagnostic value of the technique.

PURPOSE: This study was performed to assess the feasibility and possible advantages of bowel sonography after fluid filling of intestinal loops compared with conventional sonography. MATERIALS AND METHODS: Forty-five consecutive patients with known or suspected coeliac disease (35 females, ten males; age range 11-65 years) prospectively underwent sonography before and after ingestion of 750 ml of an aqueous solution of polyethylene glycol. Results before and after fluid distension were compared to assess whether luminal filling improved small-bowel visualisation. RESULTS: Luminal filling improved visualisation of intestinal features (luminal diameter, mucosal folds, parietal layers) in 77.6% of cases (marked, moderate or mild improvement in 2, 16 and 17 patients; 4.4%, 35.5% and 37.7%), respectively, and showed no change or worsening in 20% and 2.2% nine and one patient), respectively. Baseline examination showed abnormal features in 13/25 celiac patients (dilated fluid-filled loops, increased peristalsis, transient intussusception, mesenteric lymph nodes, intraperitoneal fluid). Reexamination after luminal filling showed additional abnormalities in six of the previous 13 and in three further coeliac patients. There were no false positive signs due to fluid administration. CONCLUSIONS: Luminal filling can improve visualisation of bowel walls and fold pattern and may be helpful in selected cases.

The prevalence of celiac disease and the appropriateness of the diagnosis in family medicine setting could be lower than expected.

OBJECTIVE: To assess the prevalence of celiac disease (CD) and the appropriateness of this diagnosis in the family medicine setting in Italy. PATIENTS AND METHODS: The electronic databases of 16 general practitioners working in Rome (Italy) were analyzed. The prevalence of CD according to the Italian pathology identification code issued by the Italian National Health System was assessed. In addition, patients registered as having celiac disease without being assigned a pathology identification code were interviewed. RESULTS: Overall, a population of 22,064 patients was analyzed. 91 patients had a diagnosis of CD (0.41%), 60 of whom had a pathology identification code (0.27%), and 31 did not (0.14%). 29 of these patients were interviewed, 16 (17.58% of the CD recorded patients) of whom reported being on a gluten-free or gluten restricted diet, with reported improvement in their clinical symptoms. Half of them further stated that they would not agree to resume a restriction free diet in order to make a definitive CD diagnosis, due to the risk of symptom recurrence. CONCLUSIONS: In a family medicine setting, the prevalence of CD seems to be lower than expected, and one third of patients diagnosed with CD do not fulfill all diagnostic criteria. Any effort to improve the diagnostic work-up for CD should also be made in this setting.

COVID-19 in celiac disease: a multicentric retrospective cohort study.

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

New biological agents for the treatment of the "high risk" IBD patients.

BACKGROUND: Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNFalpha agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and others. Their role in IBD therapy will be discussed in regard of the association of chronic inflammation and cancer in the gut. The risk of colorectal cancer is increased in ulcerative colitis (UC) and, to some extent, in Crohn's disease (CD). This association is well known from many years. However, the mechanisms linking chronic inflammation and carcinogenesis are beginning to be elucidated only recently. RESULTS AND CONCLUSIONS: Experimental data indicate that several cytokines could play a role in promoting tumour development. In this perspective, the anti cytokine agents could be not only powerful tools in treating inflammation but also efficacious in preventing the onset of inflammation associated colorectal cancer.

Diagnostic value of endoscopic markers for celiac disease in adults: a multicentre prospective Italian study.

AIM: Some endoscopic features of duodenal mucosa are marker of mucosal injury, the most common cause being celiac disease (CD). The aim of this study was to prospectively assess the diagnostic value of the endoscopic markers for the diagnosis of CD in the adult population undergoing routine upper endoscopy. METHODS: This was a prospective multicenter study conducted at 37 Italian endoscopic centers. A total of 509 consecutive patients submitted to routine upper endoscopy who presented one or more of following endoscopic markers were included: 1) mucosal mosaic pattern in the bulb and/or descending duodenum (DD); 2) nodularity in the bulb and/or DD; 3) scalloping of Kerkring's folds; 4) reduction in the number or absence of folds in the DD. 4 biopsies samples were taken from descending duodenum. In patients with histological findings consistent with CD, according to Oberhuber classification, sierologic test (EMA, tTGA) were performed for confirm the diagnosis. RESULTS: At endoscopy, 249 patients showed an isolated marker; 260 subjects showed a coexistence of more than one marker; 369 patients (72.5%) presented mucosal lesions at histological examination and in 347 of these patients the diagnosis of CD was confirmed by serologic markers (94.0%). For 10 patients the diagnosis remained uncertain because of negative sierology and exclusion of other other cause of mucosal lesions. The diagnosis of CD was made in 61.3% patients who showed the mosaic pattern, in 65.7% of patients with nodular mucosa, in 64.4% of patients with scalloping of folds, in 40.2% of patients with reduction of folds, and in 61.5% of patients with loss of folds and in 83.6% of patients who showed the coexistence of more than one marker. The endoscopic markers overall had a PPV of 68% for the diagnosis of CD; the markers that singularly have demonstrated a higher correlation with CD are: mosaic mucosa of DD (PPV 65.0%), nodular mucosa of the bulb and DD (PPV 75.5%), and scalloping of folds (PPV 64.4%). CONCLUSION: The study confirms the important role of endoscopy in the diagnostic process of CD not only for the bioptic sampling in patients with clinical suspicion of CD, but especially for the opportunity to evaluate alterations of the duodenal mucosa suggestive of CD in the general population and, consequently, to identify those patients who should undergo a duodenal biopsy.

Contrast-enhanced ultrasonography with SonoVue after infliximab therapy in Crohn's disease.

The introduction of biological treatments like monoclonal anti TNF-a antibodies (infliximab), is changing the clinical history of Crohn's disease (CD). The effects of these therapies are monitored emplying clinical indexes of active disease, laboratory parameters, endoscopy and histology, and also with imaging techniques. A new ultrasound contrast agent, SonoVue (Bracco SpA, Milano, Italy), is opening new perspectives in the study of microvasculature of several organs. Aim of this study is to evaluate by SonoVue enhanced ultrasonography (US) the occurrence of modifications in bowel wall microvasculature of CD patients and to correlate them with parameters of disease activity and to follow up the findings during infliximab therapy. After performing a basal color-doppler ultrasonography, the study of the affected bowel loop is performed after i.v. injection of SonoVue and the enhancement is evaluated on a qualitative basis. We report on the preliminary results obtained in twenty patients, eight of which have been treated with three infusions of infliximab (induction cycle) and evaluated at baseline and after the treatment. While at baseline we describe a positive correlation of SonoVue enhancement of the affected bowel loop with CRP, alpha1-glycoprotein and white blood cell number, after infliximab treatment in 6/8 cases a definite improvement was detected. Ultrasonographic evaluation of the changes of bowel wall enhancement after i.v. SonoVue during infliximab therapy might represent an useful, not invasive and relatively low cost imaging modality for the clinical monitoring of activity of small bowel Crohn's disease.

Early atherosclerosis in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Arterial and venous system may be involved. Moreover, mesenteric microvascular thrombosis has been hypothesised as a contributing factor in the pathogenesis of IBD. Early atherosclerosis is a clinical feature common to several inflammatory and immunological diseases in which atherothrombotic complication represents one of the most important cause of mortality and morbidity. We investigate the prevalence and the entity of the early stages of vascular disease in a population of IBD patients without the classical cardiovascular risk factors, by measuring the intima-media thickness (IMT) of the common carotid artery. We found that IBD patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid IMT and that homocysteine levels and age were independently associated with the increased arterial wall thickness.

Increased carotid intima-media thickness in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease. AIM: To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima-media thickness of the common carotid artery. METHODS: Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima-media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed. RESULTS: Common carotid artery intima-media thickness was significantly higher in inflammatory bowel disease patients (0.63 +/- 0.15 mm) compared with controls (0.53 +/- 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima-media thickness with homocysteine levels and age. CONCLUSIONS: Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima-media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Increased levels of NF-kappaB inhibitors (IkappaBalpha and IkappaBgamma) in the intestinal mucosa of Crohn's disease patients during infliximab treatment.

The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.

BACKGROUND: Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti-TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. AIM: To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti-TNF alpha and to analyse its clinical correlates. METHODS: A retrospective cohort study on all IBD patients who started anti-TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time-dependent predictors were updated at each available time point. RESULTS: Four hundred and two patients were included. Participants contributed a total of 839 person-years of follow-up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person-years. Cox-regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36-4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12-0.92; P = 0.03). CONCLUSIONS: Paradoxical psoriasis is a relevant side effect of anti-TNF alpha therapy, with an incidence rate of five per 100 person-years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti-TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.