Modelling a multiplex brain network by local transfer entropy.

This paper deals with the information transfer mechanisms underlying causal relations between brain regions under resting condition. fMRI images of a large set of healthy individuals from the 1000 Functional Connectomes Beijing Zang dataset have been considered and the causal information transfer among brain regions studied using Transfer Entropy concepts. Thus, we explored the influence of a set of states in two given regions at time t (At Bt.) over the state of one of them at a following time step (Bt+1) and could observe a series of time-dependent events corresponding to four kinds of interactions, or causal rules, pointing to (de)activation and turn off mechanisms and sharing some features with positive and negative functional connectivity. The functional architecture emerging from such rules was modelled by a directional multilayer network based upon four interaction matrices and a set of indexes describing the effects of the network structure in several dynamical processes. The statistical significance of the models produced by our approach was checked within the used database of homogeneous subjects and predicts a successful extension, in due course, to detect differences among clinical conditions and cognitive states.

Infection Control Practices and Outcomes of Endoscopy Units in the Lombardy Region of Italy: A Survey From the Italian Society of Digestive Endoscopy During COVID-19 Spread.

GOALS: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. BACKGROUND: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. METHODS: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. RESULTS: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. CONCLUSIONS: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Functional connections between and within brain subnetworks under resting-state.

The focus of this paper is on the functional role of brain regions focusing on their modular architecture and individual variability. Our main assumption is that the more variable anti-correlation patterns reflect random connections, while the more conserved ones play a functional role. Within this framework, we expanded on previous results using a different database and a different methodological approach. Aiming to identify the role of specific functional connections within a global network organization which includes subnetworks, we found that the fronto-parietal module acts as the main source of anti-correlations. In addition, the pre-frontal regions (namely: frontal middle, frontal middle orbital, frontal inferior triangular) and the parietal inferior region are highly conserved and, at the same time, act as highly connected nodes, thus confirming their importance in functional modulation.

Anticorrelations between Active Brain Regions: An Agent-Based Model Simulation Study.

Anticorrelations among brain areas observed in fMRI acquisitions under resting state are not endowed with a well-defined set of characters. Some evidence points to a possible physiological role for them, and simulation models showed that it is appropriate to explore such an issue. A large-scale brain representation was considered, implementing an agent-based brain-inspired model (ABBM) incorporating the SER (susceptible-excited-refractory) cyclic mechanism of state change. The experimental data used for validation included 30 selected functional images of healthy controls from the 1000 Functional Connectomes Classic collection. To study how different fractions of positive and negative connectivities could modulate the model efficiency, the correlation coefficient was systematically used to check the goodness-of-fit of empirical data by simulations under different combinations of parameters. The results show that a small fraction of positive connectivity is necessary to match at best the empirical data. Similarly, a goodness-of-fit improvement was observed upon addition of negative links to an initial pattern of only-positive connections, indicating a significant information intrinsic to negative links. As a general conclusion, anticorrelations showed that it is crucial to improve the performance of our simulation and, since these cannot be assimilated to noise, should be always considered in order to refine any brain functional model.

Negative functional brain networks.

The anticorrelations in fMRI measurements are still not well characterized, but some new evidences point to a possible physiological role. We explored the topology of functional brain networks characterized by negative edgess and their possible alterations in schizophrenia, using functional images of 8 healthy subjects and 8 schizophrenic patients in a resting state condition. In order to minimize the insertion of artifactual negative correlations, the preprocessing of images was carried out by the CompCorr procedure, and the results compared with the Global Signal Regression (GSR) procedure. The degree distribution, the centrality, the efficiency and the rich-club behavior were used to characterize the functional brain network with negative links of healthy controls in comparison with schizophrenic patients. The results show that functional brain networks with both positive and negative values have a truncated power-law degree distribution. Moreover, although functional brain networks characterized by negative values have not small-world topology, they show a specific disassortative configuration: the more connected nodes tend to have fewer connections between them. This feature is lost using the GSR procedure. Finally, the comparison with schizophrenic patients showed a decreased (local and global) efficiency associated to a decreased connectivity among central nodes. As a conclusion, functional brain networks characterized by negative values, despite lacking a well defined topology, show specific features, different from random, and indicate an implication in the alterations associated to schizophrenia.

2-Litre polyethylene glycol-citrate-simethicone plus bisacodyl versus 4-litre polyethylene glycol as preparation for colonoscopy in chronic constipation.

BACKGROUND: Chronic constipation is a risk factor of inadequate bowel preparation for colonoscopy; however, no large clinical trials have been performed in this subgroup of patients. AIMS: To compare bowel cleansing efficacy, tolerability and acceptability of 2-L polyethylene-glycol-citrate-simethicone (PEG-CS) plus 2-day bisacodyl (reinforced regimen) vs. 4-L PEG in patients with chronic constipation undergoing colonoscopy. METHODS: Randomized, observer-blind, parallel group study. Adult outpatients undergoing colonoscopy were randomly allocated to 2-L PEG-CS/bisacodyl or 4-L PEG, taken as split regimens before colonoscopy. Quality of bowel preparation was assessed by the Ottawa Bowel Cleansing Scale (OBCS). The amount of foam/bubble interfering with colonic visualization was also measured. RESULTS: 400 patients were enrolled. There was no significant difference in successful cleansing (OBCS score ≤6): 80.2% in the 2-L PEG-CS/bisacodyl vs. 81.4% in the 4-L PEG group. Significantly more patients taking 2L PEG-CS/bisacodyl showed no or minimal foam/bubbles in all colonic segments (80% vs. 63%; p<0.001). 2-L PEG-CS/bisacodyl was significantly more acceptable for ease of administration (p<0.001), willingness to repeat (p<0.001) and showed better compliance (p=0.002). CONCLUSION: Split 2-L PEG-CS plus bisacodyl was not superior to split 4-L PEG for colonoscopy bowel cleansing in patients with chronic constipation; however, it performed better than the standard regimen in terms of colonic mucosa visualization, patient acceptance and compliance.

Improved 5-year survival of patients with immunochemical faecal blood test-screen-detected colorectal cancer versus non-screening cancers in northern Italy.

BACKGROUND: Colorectal cancer screening may reduce disease-related mortality by early-stage detection of cancers. AIMS: To study the effect of a single immunochemical faecal occult blood test (i-FOBt) screening round on reduction in colorectal cancer-related-mortality among average risk subjects. METHODS: Comparison of 5-year mortality rates in 3 cohorts from a Northern Italian province: (1) colorectal cancers detected at the 1st biennial round of a mass-screening programme targeting 50-69 years old subjects, (2) non-screening cancers symptomatically diagnosed during the same time period, and (3) cancers detected in the pre-screening biennium. Multivariate analyses were performed with the Cox regression model including tumour node metastasis (TNM) stage at diagnosis, anatomical distribution of cancers, age at diagnosis, gender and patient group. Kaplan-Meyer survival estimates and log-rank test for equality of survivor functions were calculated. RESULTS: Stage distribution significantly differed between screening and non-screening colorectal cancers: 73% of screen-detected colorectal cancers were stages I and II versus 43% and 40% of non-screening and pre-screening colorectal cancers. Cumulative 5-year mortality rate was significantly lower in screening compared to non-screening or pre-screening colorectal cancers patients (19% versus 37% and 41%, p < 0.001). CONCLUSIONS: Colorectal cancers were detected at earlier stages in i-FOBT-positive subjects in comparison with non-screening patients; colorectal cancers found at screening had a significantly improved 5-year survival.

Medial frontal gyrus alterations in schizophrenia: relationship with duration of illness and executive dysfunction.

Executive functioning is consistently impaired in schizophrenia, and it has been associated with reduced gray matter volume in prefrontal areas. Abnormalities in prefrontal brain regions have also been related to the illness duration. The aim of the study was to investigate the effect of executive functioning decline and chronicity in prefrontal regions of patients with schizophrenia. Participants comprised 33 schizophrenic patients, 18 with duration of illness (DoI) shorter than 10 years and 15 with duration of illness longer than 10 years. In addition, 24 healthy controls served as a comparison group. Participants performed the Wisconsin Card Sorting Test (WCST) and underwent structural magnetic resonance imaging. Patients with longer DoI showed significant reduction of gray matter volume in the left medial frontal gyrus compared with healthy controls. Moreover, there was a trend for greater gray matter volume decrease in patients with a longer illness duration compared with patients with shorter illness duration. There was no interaction between the volume of the left medial frontal gyrus performance on the WCST. The present study supports the hypothesis that medial frontal gyrus alterations in schizophrenia are sensitive to duration of illness. These alterations were not associated with executive functioning.

Overall acceptability and efficacy of commonly used bowel preparations for colonoscopy in Italian clinical practice. A multicentre prospective study.

BACKGROUND & AIMS: The recent enormous increase in colonoscopy demand prompted this multicentre observational study assessing overall acceptability and efficacy of commonly used bowel preparations in Italian clinical practice. METHODS: Consecutive outpatients undergoing colonoscopy were recruited from 9 major gastroenterological centres in Italy. Each patient evaluated overall acceptability of the bowel cleansing preparation through a 0-100mm Visual Analogue Scale. The Visual Analogue Scale score was dichotomized by a median split: 80-100 (high acceptability) vs. 0-79 (low acceptability). Bowel cleansing was assessed through a validated scale. The influence of potential individual determinants on patients' acceptability and cleansing efficacy of the bowel preparations was determined by multivariate analyses. RESULTS: 599 evaluable patients were enrolled; 57.3% received 4L-PEG preparations, 29.5% 2L-PEG preparations and 13.2% 2-glasses-solutions (Na-phosphate/Mg-citrate/Na-picosulphate-containing preparations). Overall acceptability was significantly higher for 2L-PEG and 2-glasses solutions than 4L-PEG (adjusted odds ratio, 4.72; and adjusted odds ratio 2.07, respectively). Successful bowel cleansing achieved with 4L-PEG (85.9%) was similar to 2L-PEG (85.3%; adjusted odds ratio 0.82) and significantly higher than 2-glasses solutions (69.6%; adjusted odds ratio 0.34 vs. 4L-PEG). Split regimen, lower total preparation volume and colonoscopy reason (periodical control vs. 1st procedure) were significantly associated with high acceptability. Age ≥60 years, dissatisfaction with the preparation taken, and ≤4/week bowel movements were major determinants of a poor bowel cleansing. CONCLUSIONS: 2L-PEG and 4L-PEG preparations provide the most effective bowel cleansing for colonoscopy in clinical practice, with a significantly higher acceptability for 2L-PEG preparations.

[Tardive dyskinesia: diagnosis, assessment and treatment]. / Discinesia tardiva: diagnosi, valutazione e terapia.

Tardive dyskinesia is a potentially fatal side effect of antipsychotics. In the classic form is characterized by involuntary hyperkinetic movements, especially those affecting the mimic and mastication muscles. The main hypothesis considers that the pathophysiological basis of the disorder is an overexpression of D2 receptors in the striatum, in response to dopamine block neuroleptics-mediated, especially the older ones. Because fortunately not all patients undergo this severe adverse effects, many efforts have been conducted in trying to delineate the risk factors so as to try to prevent tardive dyskinesia by administering lower doses of neuroleptics in vulnerable groups. Advanced age, female sex, smoking habits, diabetes mellitus, alcohol abuse are known as risk factors. The instead the role of the type of psychiatric disorder, instead, is still debated. Since there was a direct relationship between cumulative dose of antipsychotic and treatment duration, recent studies are aimed at identifying factors that contribute to increased plasma concentrations of the drug, such as genetic polymorphisms of metabolizer enzymes that encode for enzymatic variants with decreased activity.

Consensus guidelines for the use of bowel preparation prior to colonic diagnostic procedures: colonoscopy and small bowel video capsule endoscopy.

BACKGROUND: Adequate bowel preparation prior to colonic diagnostic procedures is essential to ensure adequate visualisation. SCOPE: This consensus aims to provide guidance as to the appropriate use of bowel preparation for a range of defined clinical circumstances. A consensus group from across Europe was convened and met to discuss appropriate bowel preparation. The use of polyethylene glycol (PEG), sodium picosulphate and sodium phosphate (NaP), together with other agents, prokinetics and simethicone, in colonoscopy and small bowel video capsule endoscopy were considered. A systematic review of the literature was carried out and additional unpublished data was obtained from the members of the consensus group where required. Recommendations were graded according to the level of evidence. FINDINGS: PEG-based regimens are recommended first line for both procedures, since their use is supported by good efficacy and safety data. Sodium-picosulphate-based regimens are recommended second line as their cleansing efficacy appears less than PEG-based regimens. NaP is not recommended for bowel cleansing due to the potential for renal damage and other adverse events. However, the use of NaP is acceptable in patients in whom PEG or sodium picosulphate is ineffective or not tolerated. NaP should not be used in patients with chronic kidney disease, pre-existing electrolyte disturbances, congestive heart failure, cirrhosis or a history of hypertension. The timing of the dose, dietary restrictions, use in special patient groups and recording of the quality of bowel preparation are also considered for patients undergoing colonoscopy. During the development of the guidelines the European Society of Gastrointestinal Endoscopy (ESGE) issued guidance on bowel preparation for colonoscopy. The ESGE guidelines and these consensus guidelines share many recommendations; differences between the guidelines are reviewed. CONCLUSION: The use of bowel preparation should be tailored to the individual patient and their specific clinical circumstances.

Meta-analysis: efficacy of small bowel preparation for small bowel video capsule endoscopy.

OBJECTIVE: It is unclear whether small bowel visibility in video capsule endoscopy (VCE) is enhanced by the use of bowel preparation in addition to pre-procedural fasting. The objective of this study was to clarify this issue by means of a systematic review of the literature and meta-analysis. METHODS: Randomised controlled trials comparing the use of laxative bowel preparation with fasting alone were identified using a literature search. Categorical measures of treatment efficacy were extracted from qualifying studies and pooled using random-effects meta-analyses. Primary analysis compared any bowel preparation with fasting alone; subsidiary analyses assessed diagnostic yield and results for each regimen. RESULTS: Eight studies were identified, using either polyethylene glycol (PEG) or sodium phosphate (NaP) based regimens. No qualifying studies were identified using other laxatives. Study quality was sufficiently high to warrant meta-analysis. Use of any form of bowel preparation yielded significantly better visibility than fasting alone (OR = 2.31; 95% CI = 1.46-3.63; p < 0.0001). Similar results were seen for diagnostic yield (OR = 1.88; 95% CI = 1.24-2.84; p = 0.023). When sub-analysed according to the treatment used, PEG-based regimens showed benefit (OR = 3.11; 95% CI = 1.96-4.94; p < 0.0001), while NaP-based regimens yielded no significant difference from fasting alone (OR = 1.32; 95% CI = 0.59-2.96; p < 0.0001). LIMITATIONS: The study did not consider results from retrospective studies, nor those which did not give a categorical measure of efficacy. The impact of prokinetic and other adjunctive treatments was not considered. The results are only relevant to the most commonly used video capsule, as data for newer alternative devices have not yet been published. CONCLUSION: Based on the results of this analysis, the use of bowel preparation alongside fasting is recommended for VCE. PEG-based regimens offer a clear advantage in these patients, while the currently available evidence base does not support the use of NaP. For VCE, lower volume PEG appears to be as efficacious as higher volumes traditionally used for colonoscopy preparation.

A combination of faecal tests for the detection of colon cancer: a new strategy for an appropriate selection of referrals to colonoscopy? A prospective multicentre Italian study.

INTRODUCTION: Colonoscopy workload for endoscopy services in Western countries is increasing markedly because of the implementation of faecal occult blood-based mass screening programmes against colorectal cancer (CRC). We therefore explored the possibility of using a combination of faecal tests to prioritize the access to colonoscopy with criteria other than symptoms and/or time of referral. AIMS AND METHODS: We tested a combination of faecal tests [immunochemical faecal occult blood test (i-FOBT), M2-PK, calprotectin] as markers for advanced neoplasia in a selected series of patients requiring colonoscopy for the suspicion of CRC. All the tests were performed in a 1-day stool sample of patients aged 50-80 years, without any dietary restriction, before colonoscopy. RESULTS: A total of 280 patients' stool single samples were analysed. Forty-seven patients had CRC and 85 patients had one or more advanced adenoma(s) at colonoscopy/histology. CRCs were associated with a highly significant increase (P<0.001) in faecal tumour M2-PK (mean 24.2 kU/l), which correlated with Dukes' staging. For CRC detection, i-FOBT was the test with the highest specificity and positive predictive value (0.89 and 0.53), whereas M2-PK had the highest sensitivity and negative predictive value (0.87 and 0.96). Calprotectin showed performance similar to M2-PK in terms of sensitivity and negative predictive value (0.93), but had lower specificity (0.39). The best combination of tests to predict the risk of CRC in this series was i-FOBT+M2-PK, as in patients showing positivity to both markers, the risk of cancer was as high as 79%. CONCLUSION: The combination of i-FOBT and M2-PK is a sensitive tool in clinical practice for the appropriate management of waiting lists for colonoscopy, as it allows the classification of patients into different degrees of priority for investigation, according to their foreseeable risk of CRC.

Impact of a population-based colorectal cancer screening program on local health services demand in Italy: a 7-year survey in a northern province.

OBJECTIVES: In 2005, the National Health Service recommended a population-based colorectal cancer (CRC) screening program using biennial fecal occult blood testing (FOBT), followed by total colonoscopy in positive patients. So far, no studies have been performed to evaluate the impact of a mass-screening CRC campaign on the health system services at the community level in Italy. We have therefore assessed the workload generated by the first two biennial rounds of screening program on the activity of hospital services involved in CRC diagnosis in the Lecco province. METHODS: Routine data from all hospital services of our province were collected on activity levels related to CRC diagnosis from January 2003 to December 2009. This time span covered the 2 years prior to, as well as the two biennial rounds of the CRC screening program. In particular, we focused on the volume of outpatient FOBTs and colonoscopies (both diagnostic and interventional) performed among subjects outside the screening program. Joinpoint models were used to test whether an apparent change in trend of examination over time was statistically significant in different age cohorts of the population (<50 years, 50-69 years, and ≥70 years). RESULTS: The volume of "extra-screening" per-patient/FOBTs and colonoscopies increased significantly over the evaluated periods in all ages, until year 2008, when a steady trend was beginning; the AAPCs (average of the annual percent changes) values were 5.7, 3.1, and 8.4 for FOBT and 14.6, 13.4, and 16.7 for colonoscopy in the three age cohorts, respectively. However, the increase in both FOBT and colonoscopy demand was maximal in the cohort ≥70 years, where three statistically significant annual percent changes (APCs) were identified (in 2003-2005, 2005-2006, and 2006-2007 APCs were 12.3, 14.9, and 15.9 for FOBT, and 18.7, 36.8, and 25.4 for colonoscopy, respectively). CONCLUSIONS: After the implementation of a FOBT-based mass-screening program for CRC, careful consideration must be given to the significant increase in the workload of hospital services involved in CRC diagnosis, outside the screening campaign. The extra-work mainly involves gastroenterologists performing colonoscopy, whose activity increased over the 5-year period by 118%, as well as laboratory services, where the demand of FOBTs rose by 40%. This phenomenon, mainly attributable to a profound change in the attitude toward CRC screening by those age cohorts outside the program, covers a time span of two full rounds of screening, whereupon a steady trend for colonoscopy is apparent.

Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study.

OBJECTIVES: Mucosal healing has been proposed as an important sign of the efficacy of medical treatment of inflammatory bowel disease; however, direct evidence in ulcerative colitis (UC) is scarce. We evaluated the usefulness of colonoscopy and bowel ultrasound (US) as indexes of response to short-term therapy and as predictors of subsequent outcome in UC. METHODS: A total of 83 patients with moderate-to-severe UC were recruited; endoscopic and US severity was graded 0-3 at entry according to validated scores. Of the recruited patients, 74, who were clinically responsive to steroids, were followed up with repeated colonoscopy and bowel US at 3, 9, and 15 months from recruitment. Concordance between clinical, endoscopic, and US scores at various visits was determined by kappa statistics. Multiple unconditional logistic regression models were used to assess the predictivity of clinical, endoscopic, and US scores measured at 3 and 9 months on the development of endoscopic UC relapse within 15 months. RESULTS: A variable concordance was found over time between endoscopic and clinical score (weighted kappa between 0.38 and 0.95), with high and consistent concordance between endoscopic and US scores (weighted kappa between 0.76 and 0.90). On logistic regression analysis, moderate-to-severe endoscopic and US scores at 3 months were associated with a high risk of endoscopic activity at 15 months (odds ratio (OR): 5.2; 95% confidence interval (CI): 1.6-17.6 and OR: 9.1; 95% CI: 2.5-33.5, respectively). CONCLUSIONS: Bowel US may be used as a surrogate of colonoscopy in assessing the short-term response of severe forms of UC to therapy. Both US score and endoscopic score after 3 months of steroid therapy predict outcome of disease at 15 months.

Colorectal cancer screening in Europe: differences in approach; similar barriers to overcome.

Worldwide diagnoses of bowel cancer approximate an estimated one million new cases per year, comprising 9% of all cancer cases, and this has continued to increase over the last 25 years. With the association between cancer risk and increasing age, together with the suggestion that by 2015 there will be a 22% increase in the proportion of the population aged over 65 years and a 50% increase in the proportion of people aged over 80 years, there is likely to be a significant increase in the demand on cancer services throughout Europe and the rest of the world. This article discusses the current state of bowel cancer screening within Europe.