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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

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.

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.

Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic atrophic gastritis (AIG). Hypergastrinemia, secondary to AIG, predisposes to gastric enterochromaffin-like cell (ECL) hyperplasia, a preneoplastic condition. We evaluated the prevalence of AIG, hypergastrinemia and ECL hyperplasia in HT patients. A secondary end-point was to assess the efficacy of treatment with a somatostatin analogue in HT patient with ECL hyperplasia. From 2009 to 2011, 146 HT patients were enrolled in a prospective study. All cases underwent hormonal profile, and parietal cell antibody (PCA), gastrin, and chromogranin A (CgA) serum level assays. Selected patients with elevated gastrin and CgA levels underwent gastro esophageal endoscopy (EGDS). Patients positive for ECL hyperplasia received Octreotide LAR 30 mg/28 days for 12 months. Gastrin and CgA assays were repeated every three months and EGDS after one year. The results show that gastrin and CgA were significantly higher than normal in 17/115 (14.7%) patients. Seven more HT had isolated PCA positivity and in the 17 PCA positive patients histology diagnosed AIG, corpus prevalent, with mild to moderate atrophy. Diffuse ECL hyperplasia of the gastric body was present in three subjects, one of them presenting a type-1 carcinoid. Gastrin and CgA levels were significantly reduced (p

Background & Aims Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. Methods We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n=90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n=90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. Results Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%–95.8%) and sequential therapies (93.3%; 95% CI, 86.9%–97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%–99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%–98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; −7.6% to 9.8%) and −1.0% in the per-protocol analysis (95% CI; −8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. Conclusions Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori -infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naive to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.