Efficacy of Prucalopride in bowel cleansing before colonoscopy. Results of a pilot study

Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing is considered a big issue, because it is often poorly tolerated for many reasons (like inability to swallow large volume of liquids or unlikable taste); this can cause a suboptimal preparation that may lead to miss a neoplastic lesion. There is relatively little data about how to improve preparation tolerability. The purpose of our pilot study was to analyze the effect of prucalopride (Resolor®), a highly selective serotonin 5HT4 receptor agonist used for chronic constipation for its ability to stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy, followed by half volume of polyethylene glycol solution. We found that this can be a good and safe method to achieve an adequate and better-tolerated colon cleansing

Tertiary stent-in-stent for obstructing colorectal cancer. A case report and literature review

BACKGROUNDSelf-expandable metal stents (SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer (CRC). Among possible complications of SEMS positioning, re-obstruction is the most frequent. Its management is controversial, potentially involving secondary stent-in-stent placement, which has been poorly investigated. Moreover, the issue of secondary stent-in-stent re-obstruction and of more-than-two colonic stenting has never been assessed. We describe a case of tertiary SEMS-in-SEMS placement, and also discuss our practice based on available literature.CASE SUMMARYA 66-year-old male with occluding and metastatic CRC was initially treated by positioning of a SEMS, which had to be revised 6 mo later when a symptomatic intra-stent tumor ingrowth was treated by a SEMS-in-SEMS. We hereby describe an additional episode of intestinal occlusion due to recurrence of intra-stent tumor ingrowth. This patient, despite several negative prognostic factors (splenic flexure location of the tumor, carcinomatosis with ascites, subsequent chemotherapy that included bevacizumab and two previously positioned stents (1 SEMS and 1 SEMS-in-SEMS)) underwent successful management through the placement of a tertiary SEMS-in-SEMS, with immediate clinical benefit and no procedure-related adverse events after 150 d of post-procedural follow-up. This endoscopic management has permitted 27 mo of partial control of a metastatic disease without the need for chemotherapy discontinuation and, ultimately, a good quality of life until death.CONCLUSIONTertiary SEMS-in-SEMS is technically feasible, and appears to be a safe and effective option in the case of recurrent SEMS obstruction

Improving basic skills in celiac-like disease diagnosis. A case report

Background: The diagnosis of Coeliac disease (CD) requires a combination of sign/symptoms, positivity of specific antibodies and duodenal histological evidence of villous atrophy. Duodenal villous atrophy, despite representing the CD landmark, is not specific since it is found in many gastrointestinal disorders. Giardiasis is one of the most common human intestinal protozoan infestations in industrialized countries whose histological duodenal mucosa damage could mimic that of CD. The present report shows how a wise clinical and laboratory assessment led us shortly to a correct diagnosis. Case presentation: A 42-year-old outpatient woman without previous significant gastrointestinal diseases, was referred with dyspeptic symptoms, fatigue and mild diarrhea from 4 months. Her first investigations including immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (anti-tTG) and stool parasitological and cultural analysis were negative. An esophagogastroduodenoscopy (EGDS) showed no mucosal alteration. But histology demonstrated a Helicobacter Pylori (HP) pan-gastritis while duodenal mucosa showed villous atrophy consistent with a diagnosis of CD Marsh type 3b. While on gluten-free diet (GFD) the patient didn't experience any improvement of symptoms. Duodenal biopsies were then reviewed showing the presence of trophozoites of Giardia on the luminal surface of the duodenal wall and at the same time, a second stool examination revealed the presence of trophozoites and cysts of Giardia. Treated with metronidazole, 500 mg twice daily for 6 days the patient reduced diarrhea after few days. After about 2 months of GFD she was invited to discontinue it. At the same time stool examination was repeated with negative results. She subsequently performed eradication for Hp with triple therapy (Pylera®). Around 6 months later, the patient did not complain any gastrointestinal symptoms. Serological tests were normal and at a follow-up EGDS, duodenal mucosa had normal histology with normal finger-like villi and absence of Giardia trophozoites. Conclusion: This case report shows how CD diagnosis can sometimes be manifold. Intestinal villous atrophy alone may not automatically establish a diagnosis of CD. In the present case the clinical scenario could be fully explained by giardiasis. Indeed, different diagnostic tools and a multi-step approaches have been used to determine the final correct diagnosis

Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy

Simple Summary Pancreatic cancer is still burdened with a severe prognosis, despite advances in the diagnosis and surgical management of this disease. The gut microbiome is gaining increasing interest in the development and management in this setting. The intent of our review is to provide a comprehensive review for researchers and clinicians in the field to fully understand the role of the gut microbiome in the history of pancreatic cancer. We analyzed current literature from pre-cancerous conditions to cancer characteristics and how this may alter the therapeutic approach. Evidence and concerns can guide future research in this area. Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis

Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years. lessons learned and clinical impact

Background and study aims Outcomes of endoscopic assessment and management of large colorectal (CR) non-pedunculated lesions (LNPLs) are still under evaluation, especially in Western settings. We analyzed the clinical impact of changes in LNPL management over the last decade in a European center.Patients and methods All consecutive LNPLs >= 20mm endoscopically assessed (2008-2019) were retrospectively included. Lesion, patient, and resection characteristics were compared among clinically relevant subgroups. Multivariate logistic regression (for predictors of submucosal invasion [SMI] and recurrence), Kaplan-Meier curves and ROC curves (for temporal cut-offs in trends analyses) were used.Results A total of 395 LNPLs were included (30mm [range 20-40]; SMI=9.6%; primary endoscopic resection [ER]=88.4%). Pseudo-depression and JNET classification independently predicted SMI beyond single morphologies/location. After complete ER, involvement of ileocecal valve/dentate line, piece-meal resection and high-grade dysplasia independently predicted recurrence. Rates of 5-year recurrence-free, surgery-free and cancer-free survival were 77.5%, 98.6% and 100%, respectively, with 93.8% recurrences endoscopically managed and no death attributable to ER or CR cancer (versus 3.4% primary surgery mortality). ROC curves identified the period >= 2015 (following Endoscopic Submucosal Dissection [ESD] introduction and education on pre-resective lesion assessment) as associated with improved lesions' characterization, increased en-bloc resection of SMI lesions (87.5% vs 37.5%; p=0.0455), reduced primary surgery (7.5% vs 16.7%; p=0.0072), surgical referral of benign lesions (5.1% vs 14.8%; p=0.0019), and recurrences.Conclusions ESD introduction and educational interventions allowed ER of more complex lesions, offset by increased complementary surgery for complications or intrinsic histological risk. Nevertheless, overall, they have reduced surgery demand and increased appropriateness and safety of LNPL management in our center

Safety and efficacy of treatment with vitamin K antagonists in patients managed in a network of anticoagulation services or as routine general care

This is a retrospective, record-linkage study aimed at comparing the effectiveness and safety of two management models of vitamin K antagonists: a Network model (NAS), in which anticoagulation clinics and general practitioners (GP) share the same management software and database, and an individual General Practitioners model. Main outcomes were thromboembolic events (TE), major bleeding (MB) and all-cause mortality. Crude incidence rate and sub-distribution hazard ratio were calculated. Fine and Grey models were used to calculate SHR in multi-variable analysis. 9,418 patients in the NAS and 5,508 in the Routine General Care (RGC) cohort were included. Patients in the NAS cohort had a lower incidence of TE and mortality in respect to the RGC (sHR 0.76%, 95% CI 0.64-0.90 and 0.82%, 95% CI 0.75-0.89, respectively). More patients in the NAS than in the RGC cohort attained a Time in Therapeutic Range >60% (62.2% vs 35.7%, p<0.001). No statistically significant difference was found in MB incidence. This study shows that the NAS model for vitamin K antagonist oral anticoagulants management significantly improves the TTR and reduces the incidence of TE and mortality, without affecting the MB rate

Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6

Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV

Implications of a High-Mass Diphoton Resonance for Heavy Quark Searches

Heavy vector-like quarks coupled to a scalar $S$ will induce a coupling of this scalar to gluons and possibly (if electrically charged) photons. The decay of the heavy quark into $Sq$, with $q$ being a Standard Model quark, provides, if kinematically allowed, new channels for heavy quark searches. Inspired by naturalness considerations, we consider the case of a vector-like partner of the top quark. For illustration, we show that a singlet partner can be searched for at the 13$\,$TeV LHC through its decay into a scalar resonance in the $2\gamma+\ell + X$ final states, especially if the diphoton branching ratio of the scalar $S$ is further enhanced by the contribution of non coloured particles. We then show that conventional heavy quark searches are also sensitive to this new decay mode, when $S$ decays hadronically, by slightly tightening the current selection cuts. Finally, we comment about the possibility of disentangling, by scrutinising appropriate kinematic distributions, heavy quark decays to $St$ from other standard decay modes.Comment: 8 pages, 3 figures and 1 table; v3: typos fixed. Matches published versio

The bone marrow represents an enrichment site of specific T lymphocytes against filamentous fungi

Bone marrow has already been described as an enrichment site for several antigen-specific T lymphocytes, but the presence of mould-specific T cells has never been investigated in the bone marrow. We have previously demonstrated that mould-specific T cells emerge in the peripheral blood of patients with invasive fungal infections (IFI) but tend to become undetectable after disease resolution. In seven patients with a history of IFI, we investigated the presence of mould-specific T cells secreting different cytokines in bone marrow and peripheral blood paired samples. The results showed that the frequencies of mould-specific T cells secreting the protective cytokine IFNI3 are significantly higher in bone marrow (BM) and are mainly represented by CD8+ T lymphocytes with effector phenotype. A putative disappearance of such protective BM responses after myeloablative therapy could contribute to the increased risk of IFI in hematologic patients

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-\u3b2 protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1\u3b2 and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD