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Background: Ulcerative colitis may impair anorectal function, causing disabling symp-toms such as incontinence and/or increase in the stool frequency, urgency and tenesmus. Data on anorectal function in these patients evaluated by conventional anorectal manometry are conflicting. Objectives: The aim of this prospective study was to assess by means of high resolution anorectal manometry the anorectal function in patients with mild-to-moderate ulcerative colitis at presentation and after remission. Anorectal function of ulcerative colitis patients was compared to that observed in healthy volunteers. Methods: 20 patients with mild to moderate left-sided ulcerative colitis or proctitis and 20 healthy volunteers were prospectively enrolled. All ulcerative colitis patients underwent high resolution ano-rectal manometry before treatment and after clinical remission. Results: Ulcerative colitis patients showed similar values for anal sphincter function as healthy vol-unteers, whereas rectal threshold volume for the first sensation, desire to defecate, urgency to defecate and maximum discomfort were significantly lower than in healthy volunteers (p Conclusions: Ulcerative colitis patients show altered rectal function, with increased rectal sensitivity and lower compliance, compared to controls. This altered function is restored after successful treat-ment of the underlying inflammatory process. Finally high resolution anorectal manometry provides useful information on anorectal functionality and, in our opinion, should be preferred over conven-tional manometry.

Background: Symptomatic uncomplicated diverticular disease (SUDD) is a recognized clinical condition characterized by abdominal pain and changes in bowel habits, attributed to diverticula but without macroscopic signs of diverticulitis. There is no consensus about the management of these patients. Enteroflegin®, an association of natural active ingredients, could be effective in the treatment of those patients. Methods: We conducted a retrospective observational study to evaluate the performances of Enteroflegin® in patients with SUDD. Patients were treated with Enteroflegin® 2 cp/day for 10 days per month for 6 months. Primary endpoint was the clinical remission rate, defined as the absence of any symptoms; secondary endpoints were the impact of the treatment on reduction of symptoms, on fecal calprotectin (FC) expression, and the prevention of acute diverticulitis. Results: Three hundred and fifty patients were retrospectively enrolled (183 males, median age 64 yrs, IQR 54-70). Enteroflegin® was effective in inducing remission in 9.34% and 17.64% of patients at 3 and 6 months respectively (p

Introduction: Introduction: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT, i.e., PPIs plus high amoxicillin doses) when prescribed for H. pylorifirst-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results. The objective was to analyse the effectiveness, com-pliance and safety of HDDTin the European real clinical practice.Aims & Methods: Methods: International, multicenter, prospective non- interventional Registry aimed at evaluating the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at AEG- REDCap e-CRF up to June 2021. Patients receiving HDDT (amoxicillin 1, 000 mg three times a day plus a PPI), with or without bismuth, in any treatment line and for at least 10 days, were selected for inclusion.Results: Sixty patients received HDDT (98% compliance), 19 of them as first-line and 41 as rescue treatment (2nd–6th line). Overall HDDT effec- tiveness was 52% (per-protocol) and 51% (modified intention-to- treat, mITT). First-line and rescue treatment lines were similarly effective. Cure rates were lower when patients had previously received metronidazole (mITT 32% vs. 70%, p

Background MC3-R and MC5-R receptors belong to the complex melanocortin system, which has shown a strong immunomodulatory activity in several studies. Data on the role of these receptors in relation to inflammatory bowel disease are still missing and not fully elucidated. In this observational study we wanted to evaluate the expression profile of them in the colonic mucosa of Crohn’s Disease and Ulcerative Colitis patients both in the tracts directly affected by the disease activity and in the tracts spared. Methods We conducted on colonic biopsies of patients with histological diagnosis of inflammatory bowel disease immunohistochemical analyses in order to assess the degree of expression of MC3-R and MC5-R. Biopsies were performed on both the traits with macroscopic signs of inflammation and the macroscopically normal traits to assess whether the expression of the two receptors was different in relation to disease activity. Results In both Crohn’s disease and ulcerative colitis diseased tracts MC3-R (CD: +7.7 fold vs normal mucosa, P < 0.01; UC: +5.6 fold vs normal mucosa, P < 0.01) and MC5-R (CD: +5.5 fold vs normal mucosa, P < 0.01; UC: +8.1 fold vs normal mucosa, P < 0.01) were significantly increased compared to healthy mucosa. Conclusion MC3-R and MC5-R are expressed in the colon of patients with Crohn’s Disease and Ulcerative Colitis. In addition, expression is different with a higher degree of expression in the traits most affected by disease activity in both Crohn’s Disease and Ulcerative Colitis providing a potential use of these receptors in inflammatory bowel diseases pharmacology.

In this paper, we investigate the phenomenon of particle rebound in a viscous incompressible fluid environment. We focus on the important case of no-slip boundary conditions, for which it is by now classical that, under certain assumptions, collisions cannot occur in finite time. Motivated by the desire to understand this fascinating yet counterintuitive fluid-structure interaction, we introduce a reduced model which we study both analytically and numerically. In this simplified framework, we provide conditions which allow to prove that rebound is possible even in the absence of a topological contact. Our results lead to conjecture that a qualitative change in the shape of the solid is necessary for obtaining a physically meaningful rebound. We support the conjecture by also comparing numerical simulations performed for the reduced model with the finite element solutions obtained for the corresponding well-established PDE system.

Purpose Left ventricular assist devices (LVAD) have been developed to support cardiocirculatory function in patients with advanced heart failure, who are refractory to optimal medical treatment. This created the need to identify a professional figure for dedicated management of LVAD patients. Methods In this report, we analyzed all the accesses of all consecutive adult LVAD recipients at our outpatient care unit and the impact of VAD coordinator clinical/technical assessment on patients global management, at the time of COVID-19 pandemic in the period January to August 2020 Results During the study period, 19 LVAD patients had overall 357 contacts with the clinic, for different combinations of: advanced driveline dressing (n=280), log file analysis and technical check-up (n=200), clinical visit (n=102), ramp test (n=17). In the majority of accesses, the patient was seen by the VAD coordinator only, (n=238; 67%), mainly for driveline dressing, which was associated with technical check-ups in 89 cases.Overall, alarms were managed by technical check-ups and log file analyses in 14 cases (6 high priority alarms, 3 cases of high watt or low flow, and 5 cases of low-priority alarms). Ramp tests were performed during right heart catheterization, with contextual echocardiography performed by the VAD coordinator: in 11 out of 17 cases the ramp test led to medical therapy or LVAD settings optimization. Conclusion LVAD patients need frequent outpatients dedicated admissions for proper monitoring. The VAD coordinator is a key healthcare professional representing the main interface for LVAD patients, in support of physicians’ throughout the duration of mechanical support, to preserve optimal outcomes.

Background Ligand to the inducible T cell costimulator (ICOSL) on B cells is essential for the ICOS-dependent follicular recruitment of activated T cells. In patients with rheumatoid arthritis (RA) the IGF1-IGF1R axis is altered. Inhibition of IGF1R alleviated arthritis by reducing IL-6-dependent formation of Th17 cells.1 Here we study the role of IGF1R on CD21 +cells in experimental arthritis. Methods Female Balb/c mice were immunised with methylated BSA or with CII. Consequences of the IGF-1R inhibition for arthritis were studied in mBSA and CII-immunised mice treated with NT157 compound promoting degradation of insulin receptor substrates or using shRNA producing construct (shIGF1R). At termination three sub-populations of CD21 +cells were analysed: follicular dendritic cells (FDc, CD21 +CD19-CXCR5-); marginal zone B cells (MZBc, CD21 +CD19+CXCR5-); follicular B cells (FBc, CD21 +CD19+CXCR5+). Supernatants of LPS-stimulated splenocytes were analysed for production of cytokines, chemokines using Cytokine Array. Serum levels of antigen specific and autoantibodies were measured in an ELISA. Results In spleen of mBSA-immunised mice, ICOSL expression on CD21 +cells correlated to IGF1R (r=0.70, p=0.007). Inhibition of IGF1R induced a 20% reduction in ICOSL expression in all CD21 +subsets (p=0.007) followed by an increase in the number of MZBc (p=0.003), while FDc and FBc were unchanged. Inhibition of IGF1R had no effect on the expression of ICOS +on CD4 T cells or the subset of CXCR5 +follicular T cells. Reduction of the ICOSL +CD21+B cells was associated with lower production of IL-13. Inhibition of IGF1R signalling by NT157 and by shRNA, reduced production of CXCL13 and CXCL12, the chemokines essential for B cell migration towards follicules. In contrast, the production of chemokines CCL5 and CXCL12 preventing intra-follicular migration was increased, which explains the increase of MZBc. Additionally, the insufficient ICOSL signalling significantly reduced the production of IL-7 and IL-4, regulating class switching of B cells in germinal centres and differentiation of B cells into plasma cells. The described disbalance in the cytokines aiding B cell development led to the reduced production anti-inflammatory IL-10 and of mBSA-specific IgM (p=0.005) and increased production of autoreactive RF-IgM levels (p=0.001). Conclusions The study shows that IGF1R controls B cell development through the expression of ICOSL on CD21 +cells. Insufficient ICOSL signalling disturbs a balance between antigen-specific response and autoantibody production in experimental arthritis. Reference [1] Erlandsson MC, Toyra Silfversward S, Nadali M, Turkkila M, Svensson MND, Jonsson IM, et al. IGF-1R signalling contributes to IL-6 production and T cell dependent inflammation in rheumatoid arthritis. Biochim Biophys Acta. 2017;1863:2158–70. Disclosure of Interest None declared

Introduction Immunoglobulin D (IgD) remains an enigmatic molecule due to the limited understanding of its function both in healthy and in patients with autoimmune diseases. Objectives In this study we analysed serum IgD (sIgD) levels in patients with rheumatoid arthritis (RA) and healthy controls, paying special attention to differences related to age, gender, smoking and presence of autoantibodies Methods sIgD levels were measured in 416 individuals: 248 (184 female, 65 male) RA patients randomly selected at Sahlgrenska and Uddevalla Hospitals, and 169 (95 female, 73 male) healthy controls selected from the OLIN epidemiological study. Sandwich ELISA was developed by using mouse monoclonal antibodies for capture and goat polyclonal for detection (both SouthernBiotech). Serum samples were tested in dilution 1:5000 and sIgD was quantified after serial dilution of human serum with known IgD levels (Siemens, OTRD). The detection limit was 0.08 µg/ml. Smoking information was collected from all RA patients and controls by self-reported questionnaires. ACPA and RF were measured by automatic multiplex method (anti-CCP2) and rate nephelometry technology. Statistical analysis was performed using the Mann-Whitney test. Results Median sIgD was 38 µg/ml (IQR 14–97) in RA and 43 µg/ml (IQR 19–108) in healthy controls. sIgD was lower in RA females than RA males (p=0.039) whereas healthy controls had no gender differences in sIgD. Among the females, healthy controls 50 y (p=0.009), and to RA patients 50 y (p=0.046). sIgD was not related to the disease activity, however, RA females producing RF alone (p=0.009) and in combination with ACPA (p=0.028) had low sIgD compared to non-producers. In RA, female smokers had high sIgD compared to never (p=0.022) and former smokers (p=0.003). Smoking was not affecting sIgD in healthy controls. No consistent difference in sIgD was found in males. Conclusions The present study indicates that sIgD is influenced by age, gender, smoking and presence of autoantibodies. Low sIgD levels seem to be pathological due to their association with RA and the presence of RF and indicate a potential link between serum IgD and disease severity. Disclosure of interest None declared

Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4+ and CD8+ memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.

Background and Aim: percutaneous endoscopic gastrostomy (PEG) is an effective way of providing enteral feeding to patients with functionally normal gastrointestinal tract who cannot meet their nutritional needs because of inadequate oral intake. This retrospective study evaluated the clinical outcome of critically ill patients with high assistance level undergoing PEG in a general ICU over a 12 year period. Patients and Methods: we studied a cohort of 82 patients who underwent PEG over a 12-year period between 1 January 1999 and 31 December 2010. Patients were followed-up for 1 year after PEG placement. Results: There were no complications related either to the procedure or to the management of PEG, even in house nursing. In one patient, PEG with a collapsible bumper was successfully removed because the patient fully recovered from his neurological problem. Catheter substitution was necessary in three patients during the first year, because of stoma inflammation due to enteric reflux between the stoma and the catheter. One year after PEG, 66 patients were still alive while 16 patients died from the underlying disease during hospitalization. None of the patients with PEG had aspiration pneumonia. Conclusions: PEG, in expert hands, is a safe and effective procedure for enteral nutrition. Moreover, catheters should be chosen in relation to the duration of enteral feeding and as to whether the patient is likely to recover from his underlying disease.

Background and aim: Silybin is the main component of Silymarin with an increasing number of documented effects. The main effects attributed both in vitro and in vivo to Silybin are related to its antioxidant, antiinflammatory and cytoprotective actions. This study was designed to compare, in vitro, the effect of Silybin used as single substance, Silybin–phosphatidylcholine complex (SilPho), and derivatives of Silibinin (MpSil, GpSil, GlpSil, LipSil) on MKN28 and HepG2 cell viability and cell death after the induction of oxidative stress. Material and methods: Oxidative stress was induced by incubating HepG2 and MKN28 cells with xanthine oxidase in the presence of its substrate xanthine for periods of up to three hours. Cell viability was determined by the MTT assay. We evaluated whether X-XO increased cellular MDA, a marker of lipid peroxidation, and whether Silybin and SilPho pretreatment was able to counteract any such effect. Results: In basal conditions, the pre-incubation of MKN28 and HepG2 cells with Silybin, SilPho, and new Silibinin glycoconjugates lead to two different results. In fact, SilPho and new Silibinin glycoconjugates don’t affect cell viability, while Silybin induced a cell death of about 50%, also at the lower dose used, both in MKN28 and in HepG2 cells. The pre-incubation with Silybin and new Silibinin glycoconjugates don’t affect cell viability, while SilPho shows a protective effect. Exposure of MKN28 cells to X-XO caused a twofold increase in cellular MDA concentration compared with control untreated cells. Moreover, pretreatment with SilPho but not with Silybin significantly prevented X-XO induced increase in cellular MDA. Conclusions: This suggests that the protective effect of SilPho is partially due to inhibition of ROS induced lipid peroxidation.

Background and aim: Silybin is the main component of Silymarin with an increasing number of documented effects. The main effects attributed both in vitro and in vivo to Silybin are related to its antioxidant, antiinflammatory and cytoprotective actions. This study was designed to compare, in vitro, the effect of Silybin used as single substance, Silybin–phosphatidylcholine complex (SilPho), and derivatives of Silibinin (MpSil, GpSil, GlpSil, LipSil) on MKN28 and HepG2 cell viability and cell death after the induction of oxidative stress. Material and methods: Oxidative stress was induced by incubating HepG2 and MKN28 cells with xanthine oxidase in the presence of its substrate xanthine for periods of up to three hours. Cell viability was determined by the MTT assay. We evaluated whether X-XO increased cellular MDA, a marker of lipid peroxidation, and whether Silybin and SilPho pretreatment was able to counteract any such effect. Results: In basal conditions, the pre-incubation of MKN28 and HepG2 cells with Silybin, SilPho, and new Silibinin glycoconjugates lead to two different results. In fact, SilPho and new Silibinin glycoconjugates don’t affect cell viability, while Silybin induced a cell death of about 50%, also at the lower dose used, both in MKN28 and in HepG2 cells. The pre-incubation with Silybin and new Silibinin glycoconjugates don’t affect cell viability, while SilPho shows a protective effect. Exposure of MKN28 cells to X-XO caused a twofold increase in cellular MDA concentration compared with control untreated cells. Moreover, pretreatment with SilPho but not with Silybin significantly prevented X-XO induced increase in cellular MDA. Conclusions: This suggests that the protective effect of SilPho is partially due to inhibition of ROS induced lipid peroxidation.

Background and aim: Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Methods: Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-alpha, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Results: Colitis was associated with increased COX-2, TNF-alpha, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-alpha and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (p < 0.05) and restored all the considered biomarkers at the baseline level. Apple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24 h showing intense immunoreactivity for tissue transglutaminase. Conclusion: The efficacy of apple extract is mediated by its effects on COX-2 and TNF-alpha. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The mechanism of prolactin (PRL) unresponsiveness to repeated sulpiride (SUL) administration was investigated by means of two experimental protocols. The first one was carried on in seven male volunteers (age 24 to 34 yr) and consisted of two phases separated by a 5-day interval. In both phases 1 mg/kg of SUL was given im and repeated, 24 h later, together with either placebo (PL, 2 ml saline iv) or TRH (200 µg iv). 7–10 days later a standard TRH test (200 µg iv) was performed. In the second protocol the usual dose (1 mg/Kg im) of SUL was administered alone and, 24 h later, together with 0.1 U/Kg iv of insulin (insulin tolerance test: ITT) to six male volunteers (age 20 to 32 yr). A control standard ITT (0.1 U/Kg iv) was also performed 7–10 days later. Plasma samples for the evaluation of PRL were taken in basal conditions and at regular intervals after each drug administration. In the first protocol, PRL shQwed a significant increase (peak values at 30 min) after SUL administration in both phases (phase A: 54.8 ± 5.6 ng/ml, mean ± SE vs 6.4 ± 0.3, p < 0.001. Phase B: 77.5 ± 3.9 vs 7.0 ± 0.6, p < 0.001). Twenty-four h later, PRL levels were still higher than basal and were not affected by the administration of SUL + PL or SUL + TRH. Also in the second protocol, SUL alone induced a significant PRL increase (peak values at 30 min: 47.1 ± 7.2 vs 4.2 ± 0.5, p < 0.005). Twenty-four h later PRL levels were still higher than in basal conditions (12.4 ± 1.5, p < 0.01 vs day one) and were modified by SUL + ITT administration only mildly (at 60 min: 17.0 ± 2.8, p < 0.05 vs basal) and significantly less than what observed after SUL and insulin alone (p < 0.005, p < 0.05, respectively). SUL then seems to induce a prolonged unresponsiveness of pituitary PRL secreting cells to multiple administration apparently not overcome by different stimuli (TRH, ITT), probably due to an alteration distal to the dopamine receptor.

A case of an actinomycotic brain abscess in an adult patient apparently free of systemic infection is presented. The rarity of this etiology of brain abscess is underlined. The patient was treated by complete surgical excision and prolonged antibiotic therapy with penicillin. The authors stress the importance of taking into account this infrequent cause of brain abscess, the necessity of radical surgical treatment followed by intensive, prolonged and adequate antibiotic therapy, as the only means of reducing the high mortality rate.

The effect of administration of an LHRH-analogue (LHRH-a) was evaluated in 11 patients with benign prostatic hyperplasia (BPH) in whom there were contraindications for surgery. These patients, who already had impaired potency due to age or serious illness, were given 1500 micrograms LHRH-a in the first week and 1200 micrograms from the eighth day onwards. They all improved significantly (P less than 0.001) with regard to their urological symptoms on day 60 of treatment. Our results demonstrate the influence of androgen in maintaining established BPH, the effectiveness of LHRH-a therapy in selected patients with BPH and the usefulness of a salivary testosterone assay for the follow-up of treatments expected to lower the bioavailability of androgen to target tissues.

Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/l and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low- or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment.

A case of onychomycosis due to Candida Albicans in an otherwise healthy girl is reported. A vaccine was prepared with the same strain as the Candida Albicans isolated from the nail culture, broken down into 12 ampoules containing progressive concentrations. An improvement was achieved up to complete cure and this persists many months later. The results of the therapy are commented on.