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Living a Big Data era in Biomedicine, there is an unmet need to systematically assess experimental observations in the context of available information. This assessment would offer a means for an unbiased validation of the results and provide an initial estimate of the potential novelty of the findings. Here we present BQsupports, a web-based tool built upon the Bioteque biomedical descriptors that systematically analyzes and quantifies the current support to a given set of observations. The tool relies on over 1,000 distinct types of biomedical descriptors, covering over 11 different biological and chemical entities, including genes, cell lines, diseases and small molecules. By exploring hundreds of descriptors, BQsupports provide support scores for each observation across a wide variety of biomedical contexts. These scores are then aggregated to summarize the biomedical support of the assessed dataset as a whole. Finally, the BQsupports also suggests predictive features of the given dataset, which can be exploited in downstream machine learning applications.

Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Background The role of vaccination on Covid-19 severity in neurological patients is still unknown. We aim at describing clinical characteristics and outcomes of breakthrough and unvaccinated Covid-19 patients hospitalized for neurological disorders. Methods Two hundred thirty-two Covid-19 patients were admitted to a neuro-Covid Unit form March 2021 to February 2022. Out of the total sample, 74 (32%) were full vaccinated. The prevalence, clinical characteristics and final outcomes of neurological syndromes were compared between vaccinated and unvaccinated cases. Results Breakthrough vaccinated cases were older (years 72.4+16.3 vs 67.0+18.9 years, p=0.029), showed higher pre-admission comorbidity score and Clinical Frailty scale score (4.46+1.6 vs 3.75+2.0, p=0.008) with no differences in terms of disease progression or mortality rate (16.2% vs 15.2%), compared to full-dose vaccinated patients. Cox-regression analysis showed age and NEWS2 score as the variables with a significant relation to mortality between the two groups, independently from pre-morbid conditions and inflammatory response. Conclusion This study on breakthrough COVID-19 infection could help identify vulnerable neurological patients with higher risk of poor outcomes.

ObjectiveTo investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH).MethodsWe performed a case–control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1–Q4).ResultsWe analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively).ConclusionsOur findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by progressive degeneration of motor neurons (MNs). Most cases are sporadic, whereas 10% are familial. The pathological mechanisms underlying the disease are partially understood, but it is increasingly being recognized that alterations in RNA metabolism and deregulation of microRNA (miRNA) expression occur in ALS. In this study, we performed miRNA expression profile analysis of iPSC-derived MNs and related exosomes from familial patients and healthy subjects. We identified dysregulation of miR-34a, miR-335 and miR-625-3p expression in both MNs and exosomes. These miRNAs regulate genes and pathways which correlate with disease pathogenesis, suggesting that studying miRNAs deregulation can contribute to deeply investigate the molecular mechanisms underlying the disease. We also assayed the expression profile of these miRNAs in the cerebrospinal fluid (CSF) of familial (fALS) and sporadic patients (sALS) and we identified a significant dysregulation of miR-34a-3p and miR-625-3p levels in ALS compared to controls. Taken together, all these findings suggest that miRNA analysis simultaneously performed in different human biological samples could represent a promising molecular tool to understand the etiopathogenesis of ALS and to develop new potential miRNA-based strategies in this new propitious therapeutic era. ispartof: CELLULAR AND MOLECULAR LIFE SCIENCES vol:79 issue:3 ispartof: location:Switzerland status: published

Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.

Objective The aim of this study is to evaluate the differences in clinical presentations and the impact of healthcare organization on outcomes of neurological COVID-19 patients admitted during the first and second pandemic waves. Methods In this single-center cohort study, we included all patients with SARS-CoV-2 infection admitted to a Neuro-COVID Unit. Demographic, clinical, and laboratory data were compared between patients admitted during the first and second waves of the COVID-19 pandemic. Results Two hundred twenty-three patients were included, of whom 112 and 111 were hospitalized during the first and second pandemic waves, respectively. Patients admitted during the second wave were younger and exhibited pulmonary COVID-19 severity, resulting in less oxygen support (n = 41, 36.9% vs n = 79, 70.5%, p p = 0.004). The different healthcare strategies and early steroid treatment emerged as significant predictors of mortality independently from age, pre-morbid conditions and COVID-19 severity in Cox regression analyses. Conclusions Differences in healthcare strategies during the second phase of the COVID-19 pandemic probably explain the differences in clinical outcomes independently of disease severity, underlying the importance of standardized early management of neurological patients with SARS-CoV-2 infection.

ObjectiveTo explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients.MethodsIn a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method.ResultsOf the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th–75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798).ConclusionsDiscontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.

Background and purpose Whether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined.Methods In the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored.Results In all, 1738 patients (1017 [58.5%] men, mean age 67.9 +/- 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3-fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58-5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07-3.16) and in patients aged

Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. Results Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17–5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. Conclusions Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD–). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13–2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06–18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26–0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58–7.31] and 2.07 [95% CI, 1.06–4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.

ObjectiveAim of this study was to analyse the impact of COVID-19 on clinical and laboratory findings and outcome of neurological patients consecutively admitted to the emergency department (ED) of a tertiary hub center.MethodsAll adult patients consecutively admitted to the ED for neurological manifestations from February 20th through April 30th 2020 at Spedali Civili of Brescia entered the study. Demographic, clinical, and laboratory data were extracted from medical records and compared between patients with and without COVID-19.ResultsOut of 505 consecutively patients evaluated at ED with neurological symptoms, 147 (29.1%) tested positive for SARS-CoV-2. These patients displayed at triage higher values of CRP, AST, ALT, and fibrinogen but not lymphopenia (pConclusionsCOVID-19 impacts on clinical presentation of neurological disorders, with higher frequency of stroke, encephalitis and delirium, and was strongly associated with increased hospitalisation, mortality and disability.

Cervical artery dissection (CeAD) is the most common cause of ischemic stroke in young and middle-aged adults. Over the last decade, a relation between CeAD and fibromuscular dysplasia (FMD), an idiopathic, segmental, non-atherosclerotic and non-inflammatory arterial disease, has been suggested based on a number of epidemiologic observations, while preliminary data support the idea that the two conditions may share common biologic mechanisms. In this article, we review the literature on the relation between CeAD and FMD, focus on the potential pathogenetic mechanisms common to the two conditions, summarize clinical features, management and outcome, and provide support to the hypothesis that the coexistence of the two diseases in one individual might be conceptualized as a distinct non-atherosclerotic non-inflammatory arteriopathy.

ObjectiveTo report the clinical and laboratory characteristics, as well as treatment and clinical outcomes of patients admitted for neurological diseases with COVID-19 in a Neuro-COVID unit compared to patients without COVID-19.MethodsIn this retrospective, single centre cohort study, we included all adult inpatients with confirmed COVID-19, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records.Results173 patients were included in this study, of whom 56 resulted positive for COVID-19 and 117 resulted negative for COVID-19. Patients with COVID-19 were older, had a different distribution regarding admission diagnoses, including cerebrovascular disorders, and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (all pIn-hospital mortality rates and incident delirium were significantly higher in the COVID-19 group (all pppMultivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio 4.47, 95% CI 1.21-16.5; p=0.025), lower platelet count (0.98, 0.97-0.99; p=0.005) and higher lactate dehydrogenase (1.01, 1.00-1.03; p=0.009) on admission.ConclusionsCOVID-19 patients admitted with neurological disease, including stroke, have a significantly higher in-hospital mortality, incident delirium and higher disability than patients without COVID-19.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently under investigations. The hypothesis that CADASIL is an appropriate model to explore the pathogenesis of sporadic cerebral small vessel disease is also reviewed.

ObjectiveTo report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19).MethodsIn this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period.ResultsOne hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0–83.8 years vs 70.1 years, IQR 52.9–78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7–1.1 vs 0.5, IQR 0.4–0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0–6.0 vs 2.0, IQR 1.0–3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21–16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97–0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00–1.03, p = 0.009) on admission.ConclusionsPatients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

Celiac disease is the most common autoimmune enteropathy in Western countries, and is usually associated with a good response to the gluten free diet and an excellent prognosis. However, a minority of patients develop complications of the disease, such as refractory celiac disease, ulcerative jejunoileitis and neoplastic complications such as adenocarcinoma of the small bowel and enteropathy associated T cell lymphoma. Neoplastic complications described in association with celiac disease have a high mortality rate, due to their aggressive behavior and to the usual advanced stage at the time of diagnosis. In recent years, the detection of small bowel lesions has dramatically improved thank to the availability of highly performing radiologic and endoscopic techniques. The diagnostic delay of malignant complications in patients with celiac disease may be improved by establishing a pragmatic flowchart for the identification and follow up of "at risk" patients. We performed a comprehensive review of the articles published on this issue in order to promote a roadmap to be applied when facing with celiac patients with suspected small bowel complications.

BACKGROUND Indications to double-balloon enteroscopy (DBE) are not standardized in celiac disease (CD). GOALS To evaluate the clinical usefulness of DBE in complicated CD. STUDY DBE findings in celiac patients with suspected small bowel (SB) complications were retrospectively evaluated in 2 tertiary referral centers (Milan and Sheffield). Demographic data of the studied cohort were compared with a database of 1000 noncomplicated CD patients. RESULTS Twenty-four CD cases (12 males, P=0.01 vs. controls) were reviewed. Mean age at CD diagnosis (y±SD) was 37±20 versus 27±18 and at SB evaluation 47±15 versus 38±13 (P

To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses.From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined.Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P.001 for both), without significant improvement in sensitivity or AUC.Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity.

Background and Aims Enteroscopy (wireless or wired) is the reference standard for small-bowel (SB) diseases, and it has been applied to detect SB malignancies in complicated celiac disease (CD) with heterogeneous results. The aim of this meta-analysis was to obtain a diagnostic yield (DY) by pooling the data of studies that investigated the use of enteroscopy to detect SB adverse events in CD. Methods We performed an online search for studies estimating the DY of wireless and wired enteroscopy in predicting the presence of SB premalignant and/or malignant lesions. The DerSimonian and Laird random-effects method was used to pool the arcsine-transformed proportions of patients with the events. Three meta-analyses were performed considering the following events: the presence of a malignancy, premalignant damage (ulcerative jejunoileitis [UJ]), or the presence of a malignancy or UJ. A subgroup analysis was performed after extracting (if possible) patients with refractory CD (RCD). Results Of the 529 titles initially resulting from the search, 10 studies on capsule enteroscopy (CE) and 3 on double-balloon or push enteroscopy met the inclusion criteria. Overall, 439 and 76 patients were enrolled in these studies using CE and enteroscopy, respectively. Twelve tumors and 47 UJs were found by CE versus 8 tumors and 13 UJs detected by wired enteroscopy. For malignancies the CE yield was 1.9% (95% CI, .5%-3.8%) and wired enteroscopy yield 8.7% (95% CI, 0%-21.2%); similarly, for UJ the DYs were 8.4% (95% CI, 2.1%-17.7%) and 16.7% (95% CI, 8.7%-26.3%); for either UJ or neoplasia the DYs were 13.0% (95% CI, 5.6%-22.5%) and 27.7% (95% CI, 14.8%-42.6%). For RCD the DYs of all enteroscopic techniques were 1.8% (95% CI, 0%-7.7%) for neoplasia, 22.3% (95% CI, 8.2%-39.7%) for UJ, and 27.5% (95% CI, 13.1%-44.2%) for either. Conclusions Enteroscopy is a powerful and efficient diagnostic tool for the detection of SB malignancies in complicated CD.

CD (coeliac disease) is a frequent autoimmune disorder of the small bowel, which is characterized by an immunological reaction against gluten and transglutaminase in genetically predisposed subjects. However, the molecular determinants underpinning CD pathogenesis are yet to be fully elucidated and little data are available about the involvement of miRNAs (microRNAs) in CD. In the present study, the duodenal mucosa miRNA expression was profiled in adult untreated CD presenting with a classic phenotype or iron-deficiency anaemia, treated patients with or without duodenal normalization, and non-CD subjects as controls. Deregulation of seven miRNAs (miR-31-5p, miR-192-3p, miR-194-5p, miR-551a, miR-551b-5p, miR-638 and miR-1290) was determined in a larger series of CD patients with different clinical phenotypes compared with non-CD subjects. These seven microRNAs were then analysed in duodenal fibroblasts obtained from CD patients and incubated with gliadin peptides (13- and 33-mer). The miRNA cluster miR-192/194, involved in matrix remodelling, was deregulated in CD according to the different clinical presentations, and miR-192-3p levels were modulated by gliadin peptides in vitro. In conclusion, the analysis of miRNAs deserves further consideration for its potential use in the treatment and management of CD. © 2014 Biochemical Society.

Background A subset of celiac patients shows a high risk for small bowel malignancies. Aims To select celiac patients considered at risk and evaluate the diagnostic yield of enteroscopy in this context. Methods Celiac patients were enrolled from a tertiary referral centre during the period June 2011–June 2013, based on the following criteria: (i) patients diagnosed when aged 50+ and with poor response to gluten-free dieting; (ii) low dietary compliance; (iii) alarm symptoms. The patients underwent small bowel capsule endoscopy and/or double-balloon enteroscopy. Control populations were represented by the 165 non-celiac patients undergoing capsule endoscopy for obscure gastrointestinal bleeding, and the 815,362-strong population of the Italian province of Varese as a registered cohort. Results Fifty-three patients (19% males, mean age 43.6 ± 17.4 years) were evaluated. Two jejunal adenocarcinomas and one ileal neuro-endocrine tumour were diagnosed by enteroscopy (the diagnostic yield for malignancies in the selected population being 5.7%). In the non-celiac controls the detection rate of small bowel tumours by capsule endoscopy was 0.6% ( P = 0.04). When compared to the registered population, the relative risk for intestinal malignancy was 1282 (95% CI, 407–4033; P Conclusions Capsule endoscopy and double-balloon enteroscopy can be considered for early disease management of a subset of celiac patients.

Introduction The indications for and efficacy of device-assisted enteroscopy is not standardised in coeliac disease (CD). We present the largest study to date to evaluate the clinical role of double-balloon enteroscopy (DBE) in complicated CD. Methods DBE findings in CD patients with suspected small bowel complications were retrospectively evaluated in two tertiary referral centres (Milan and Sheffield). Demographic data of the studied cohort were compared with a database of 1000 non complicated CD patients. Results Findings from 14 oral and seven anal DBE in 19 CD cases (11 males p = 0.003 vs control database) were reviewed. Mean age at CD diagnosis (37 ± 19 vs. 27 ± 18) and at small bowel evaluation (49 ± 15 vs. 38 ± 13) was significantly higher in the DBE group compared to controls (p Conclusion This is the largest international DBE outcomes study in CD patients. Even minor mucosal lesions seen at DBE may be associated with significant pathology. Evaluation of non-responsive/refractory symptoms by DBE was associated with older patients (p Disclosure of Interest None Declared.

Background TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not completely understood and no data are available regarding the potential tumorigenic properties of the multiple isoforms generated by alternative splicing (AS). Methods We evaluated TMEM16A AS pattern, isoforms distribution and Splicing Coordination (SC), in normal tissues and breast cancers, through a semi-quantitative PCR-assay that amplifies transcripts across three AS exons, 6b, 13 and 15. Results In breast cancer, we did not observe an association either to AS of individual exons or to specific TMEM16A isoforms, and induced expression of the most common isoforms present in tumors in the HEK293 Flp-In Tet-ON system had no effect on cellular proliferation and migration. The analysis of splicing coordination, a mechanism that regulates AS of distant exons, showed a preferential association of exon 6b and 15 in several normal tissues and tumors: isoforms that predominantly include exon 6b tend to exclude exon 15 and vice versa. Interestingly, we found an increase in SC in breast tumors compared to matched normal tissues. Conclusions As the different TMEM16A isoforms do not affect proliferation or migration and do not associate with tumors, our results suggest that the resulting channel activities are not directly involved in cell growth and motility. Conversely, the observed increase in SC in breast tumors suggests that the maintenance of the regulatory mechanism that coordinates distant alternative spliced exons in multiple genes other than TMEM16A is necessary for cancer cell viability.