Search

Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs.A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy.The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction 10 % also predicted the risk of decompensation after SVR24.The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.ZIEL: Über das Risiko einer hepatischen Dekompensation (HD) nach direkt antiviral wirksamen Substanzen (DAA) bei Patienten mit fortgeschrittener chronischer Lebererkrankung gibt es nur wenig Evidenz. Unser Ziel war es, das Risiko einer Dekompensation und den prognostischen Wert nichtinvasiver Tests wie Messungen der Lebersteifigkeit (LSM) und Milzsteifigkeit (SSM) zur Vorhersage einer Dekompensation nach anhaltendem virologischem Ansprechen (SVR) unter DAA zu bewerten.Kohortenstudie mit 146 Zirrhose-Patienten, die in unserem Tertiärzentrum mit DAAs behandelt wurden, wobei LSM und SSM sowohl vor als auch 6 Monate nach der Behandlung verfügbar waren (SVR24). Eine historische Kohorte von 92 konsekutiven zirrhotischen Patienten mit aktiver HCV wurde als Kontrollgruppe verwendet. Um die Unterschiede zwischen den Gruppen zu berücksichtigen, wurde die Propensity-Score-Methode („inverse probability weighting“) verwendet. Zeitabhängige Modelle zur Prädiktion der Dekompensation wurden angewandt, um Veränderungen in den nichtinvasiven Tests nach Therapie zu berücksichtigen.Die Dekompensations-Inzidenz in der DAA-Kohorte betrug 7,07 (4,56–10,96) pro 100 Personenjahre (PYs), was signifikant niedriger war als in der aktiven HCV-Kohorte. Die DAA-Therapie war ein unabhängiger protektiver Faktor für die Entwicklung einer HD (SHR: 0,071; 95 %-KI 0,015–0,332). SSM ≥ 54kPa war trotz erfolgreichem SVR unabhängig mit Dekompensation assoziiert (SHR: 4,169; 95 %-KI 1,050–16,559), zusammen mit früher aufgetretener Dekompensation (SHR: 7,956; 95 %-KI 2,556–24,762). Eine SSM-Reduktion 10 % sagte auch das Risiko einer Dekompensation nach SVR24 voraus.Das Risiko einer Dekompensation war nach DAA-Therapie deutlich reduziert, aber nicht eliminiert. Gepaarte SSM-Werte stratifizierten das Risiko einer Dekompensation nach SVR besser als andere nichtinvasive Tests.

Purpose Although a few recent articles describe adults with treatment-resistant anorexia nervosa (TR-AN), no study addresses the specific features of subjects not responding to treatment in the developmental age. This study reports on the clinical and psychopathological variables that distinguish children and adolescents who did not respond to treatment (here “TR-AN”) from good-outcome controls, in a multidisciplinary hospital treatment setting. Methods Naturalistic, case–control study conducted on individuals showing lack of response to treatment and good-outcome controls. TR-AN was defined as two or more incomplete admissions and no complete admissions, consistently with studies in adults. Good-outcome was defined as complete first admission, availability for follow-up visit after 6 months, and maintaining at follow-up a %BMI > 70% in the absence of binging or purging in the preceding 3 months. Psychopathological (Eating Disorders Inventory-3 EDI-3; Beck Depression Inventory-II), clinical, and treatment variables at admission were compared. Significant differences in the univariate analyses were included in an exploratory binary logistic regression. Results Seventy-six patients (30 TR-AN, 46 good-outcome AN controls) were enrolled (mean age 14.9 ± 1.9 years, F = 94.7%). TR-AN individuals had a higher age at admission and higher EDI-3 Eating Disorder Risk (EDRC) scores, were treated less frequently with a nasogastric tube (NGT), and achieved a lower BMI improvement at discharge than good-outcome controls. A predictive model for TR-AN status was found (X2 = 19.116; Nagelkerke-R2 = 0.478, p p = 0.019), EDI-3 EDRC (OR = 0.938, p = 0.043), and NGT (OR = 8.003, p = 0.019) were associated with a TR-AN status. Conclusions This is the first report on the psychopathological and clinical characteristics of children and adolescents not responding to treatment. These patients showed higher age and eating disorder scores, and were less frequently fed with NGT than controls. Despite the multiple incomplete admissions of our subjects, the short included follow-up limits the possibility for direct comparisons with adult samples of treatment-resistant patients. Thus, the specific features of children and adolescents with TR-AN should be assessed in longitudinal studies. Level of evidence III, Observational, case–control study.

open 13 no Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complication affecting patients undergoing hematopoietic stem cell transplantation (HSCT). The survival rate is higher when specific therapy is initiated early; thus, improving early, noninvasive diagnosis of VOD/SOS is an important need. In an adult population undergoing HSCT, we aimed to assess the role of liver stiffness measurement (LSM), evaluated by transient elastography (TE), for diagnosing VOD/SOS. Between April 2016 and March 2018, 78 consecutive adult patients with indications for allogeneic HSCT were prospectively included. LSM was performed before HSCT and at days +9/10, +15/17, and +22/24 post-HSCT. New European Society for Blood and Marrow Transplantation criteria were used to establish VOD/SOS diagnosis. Four patients developed VOD/SOS (5.1%) during the study period, with a median time of +17 days post-HSCT. A sudden increase in LSM compared with previously assessed values and pre-HSCT values, was seen in all patients who developed VOD/SOS. LSM increases occurred from 2 to 12 days before clinical SOS/VOD appearance. The VOD/SOS diagnostic performance of increased LSM over pre-HSCT assessment showed an area under the receiver operating characteristic curve of 0.997 (sensitivity 75%; specificity 98.7%). LSM gradually decreased following successful VOD/SOS-specific treatment. Interestingly, LSM values did not increase significantly in patients experiencing hepatobiliary complications (according to the Common Terminology Criteria) other than VOD/SOS. LSM by TE can be considered a promising method to perform an early, preclinical diagnosis and follow-up of VOD/SOS. open open Antonio, Colecchia; Federico, Ravaioli; Mariarosaria, Sessa; Vanessa, Alemanni Luigina; Elton, Dajti; Giovanni, Marasco; Amanda, Vestito; Maurizio, Zagari Rocco; Barbato, Francesco; Mario, Arpinati; Michele, Cavo; Davide, Festi; Francesca, Bonifazi Antonio, Colecchia; Federico, Ravaioli; Mariarosaria, Sessa; Vanessa, Alemanni Luigina; Elton, Dajti; Giovanni, Marasco; Amanda, Vestito; Maurizio, Zagari Rocco; Barbato, Francesco; Mario, Arpinati; Michele, Cavo; Davide, Festi; Francesca, Bonifazi

none 7 no Sleep-related disorders have been reported to have a higher prevalence in multiple sclerosis (MS) than in the general population. They are often undervalued for the presence of more severe physical problems and the occurrence at night, without a direct observation in common clinical practice, but if not recognized and treated they can negatively affect the quality of life causing daytime drowsiness and worsening fatigue. Sleep related disorders most commonly reported in MS are as follows: insomnia, sleep-related breathing disorders (SRBD), restless legs syndrome (RLS) and periodic limb movement disorders (PLMD). Secondary narcolepsy, REM sleep behavior disorder (RBD) and propriospinal myoclonus have been also described in some case reports or series. The purpose of this review is to correlate the more common sleep disturbances in MS patients to the involvement of specific brain regions, analyzing their relationship with MRI findings. While insomnia is usually secondary to other disabling symptoms such as nocturia or pain, SRBD, RLS, narcolepsy, RBD and propriospinal myoclonus in MS patients can be the consequence of an injury of specific central nervous system (CNS) areas. Lesions in the pontine tegmentum and the dorsal medulla have been associated with SRBD, spinal cord lesions or atrophy with RLS, bilateral lesions in the lateral hypothalamus with narcolepsy-like symptoms, lesions in the dorsal pontine tegmentum with RBD and intramedullary demyelinating plaques in spinal cord with propriospinal myoclonus. MS specialists and general neurologists should be aware of these comorbidities since neuroimaging, which is routinely performed in MS, could provide helpful clinical indications on patients with secondary sleep-related disorders and to categorize symptomatic patients who need to underdo more in-depth sleep studies. mixed Foschi, M.; Rizzo, G.; Liguori, R.; Avoni, P.; Mancinelli, L.; Lugaresi, A.; Ferini-Strambi, L. Foschi, M.; Rizzo, G.; Liguori, R.; Avoni, P.; Mancinelli, L.; Lugaresi, A.; Ferini-Strambi, L.

none 8 si Background: Fibromyalgia (FM) is a complex syndrome incorporating many features associated with poor outcome in orthopaedic surgery. Aim of the present review was to comprehensively characterize the available evidence on the consequences of pre-existent FM on the outcomes of orthopaedic surgery. Methods: We performed a systematic search in MedLine and Web of Science (WOS) to identify studies evaluating the effect of FM on patient-centred outcomes, opioids consumption and postoperative complications. Results: The search strategy identified 519 records in PubMed and 507 in WOS. A total of 27 articles were deemed eligible for inclusion in qualitative synthesis. Based on quality assessment, 10 studies were rated as good quality, 10 as fair quality and 7 as poor quality. Studies reporting the prevalence of FM in consecutive patients undergoing orthopaedic surgery (n = 19) were included in quantitative synthesis. The pooled prevalence of FM in patients undergoing orthopaedic surgery was 4.1% (95% CI: 2.4-6.8) in those receiving hip or knee surgery, 10.1% (95% CI: 5.7-17.2) in those receiving shoulder or elbow surgery and 21.0% (95% CI: 18.5-23.7) in those receiving spinal surgery. The results of our systematic review consistently report FM as a significant risk factor for less satisfaction, higher pain, worse functional outcome, increased risk for postoperative opioids prescription and higher rate of medical and surgical complications following orthopaedic surgery. Conclusion: Identifying pre-existing FM in patients scheduled for elective orthopaedic surgery may help to better assess the benefit/risk ratio, improve patients' awareness and minimize any discrepancy between expectancy and results. none D'Onghia, Martina; Ciaffi, Jacopo; McVeigh, Joseph G; Di Martino, Alberto; Faldini, Cesare; Ablin, Jacob N; Meliconi, Riccardo; Ursini, Francesco D'Onghia, Martina; Ciaffi, Jacopo; McVeigh, Joseph G; Di Martino, Alberto; Faldini, Cesare; Ablin, Jacob N; Meliconi, Riccardo; Ursini, Francesco

none 6 no Guided bone regeneration is a frequently used surgical procedure for hard tissue reconstruction when horizontal and or/vertical augmentation are needed. The treatment concept is based on the application of occlusive membranes like non-resorbable membranes or titanium mesh plus resorbable membranes. However, there are no studies comparing the microcomputed tomography results for bone obtained using these two procedures, and this was the purpose of the present study. mixed Cucchi, Alessandro; Vignudelli, Elisabetta; Sartori, Maria; Parrilli, Annapaola; Aldini, Nicolò Nicoli; Corinaldesi, Giuseppe Cucchi, Alessandro; Vignudelli, Elisabetta; Sartori, Maria; Parrilli, Annapaola; Aldini, Nicolò Nicoli; Corinaldesi, Giuseppe

Background CPFA is an extracorporeal treatment used in severe sepsis to remove circulating proinflammatory cytokines. Limited evidence exists on the effectiveness of bilirubin adsorption by the hydrophobic styrenic resin, the distinctive part of CPFA. The aim of this study is to validate CPFA effectiveness in liver detoxification. Methods In this prospective observational study, we enrolled patients with acute or acute-on-chronic liver failure (serum total bilirubin > 20 mg/dL or MELD Score > 20) hospitalized from June 2013 to November 2017. CPFA was performed using the Lynda (Bellco/MedTronic, Mirandola, Italy) or the Amplya (Bellco/MedTronic, Mirandola, Italy) machines. Anticoagulation was provided with unfractionated heparin or citrate. Bilirubin and bile acids reduction ratios per session (RRs) were the main parameters for hepatic detoxification. Results Twelve patients with acute (n = 3) or acute-on-chronic (n = 9) liver failure were enrolled. Alcohol was the main cause of liver disease. Thirty-one CPFA treatments of 6 h each were performed, 19 with heparin and 12 with citrate. RRs was 28.8% (range 2.2–40.5) for total bilirubin, 32.7% (range 8.3–48.9) for direct bilirubin, 29.5% (range 6.5–65.4) for indirect bilirubin and 28.9% (16.7- 59.7) for bile acids. One patient received liver transplantation and 8/9 were alive at 1 year of follow-up. Three patients (25%) died: 2 during hospitalization and 1 for a cardiac event at 4 months of follow up with restored liver function. Conclusions CPFA resulted to be effective in liver detoxification. Thus, it may be considered as a “bridge technique” both to the liver transplant and to the recovery of the basal liver function.

open 8 no Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period. Methods: Infants

open 23 no Correction to: Scientific Reports https ://doi.org/10.1038/s4159 8-020-62979 -9, published online 08 April 2020This Article contains an error in the order of the Figures. Figures 1, 2 and 3 were published as Figures 2, 3 and 1 respectively. The correct Figures appear below as Figures 1, 2 and 3. The Figure legends are correct. This Article contains an error in the order of the Figures. Figures 1, 2 and 3 were published as Figures 2, 3 and 1 respectively. The correct Figures appear below as Figures 1, 2 and 3. The Figure legends are correct. open Ravaioli M.; De Pace V.; Angeletti A.; Comai G.; Vasuri F.; Baldassarre M.; Maroni L.; Odaldi F.; Fallani G.; Caraceni P.; Germinario G.; Donadei C.; Malvi D.; Del Gaudio M.; Bertuzzo V.R.; Siniscalchi A.; Ranieri V.M.; D'Errico A.; Pasquinelli G.; Morelli M.C.; Pinna A.D.; Cescon M.; La Manna G. Ravaioli M.; De Pace V.; Angeletti A.; Comai G.; Vasuri F.; Baldassarre M.; Maroni L.; Odaldi F.; Fallani G.; Caraceni P.; Germinario G.; Donadei C.; Malvi D.; Del Gaudio M.; Bertuzzo V.R.; Siniscalchi A.; Ranieri V.M.; D'Errico A.; Pasquinelli G.; Morelli M.C.; Pinna A.D.; Cescon M.; La Manna G.

Simple Summary Immunotherapy against PD-1/PD-L1 dramatically improved outcomes in non-small cell lung cancer patients. These treatments are more effective the higher the expression of PD-L1 on tumor cells, reported as tumor proportion score. However, PD-L1 expression can be highly variable, depending on different mechanisms of regulation. These mechanisms are usually grouped in intrisc (including genetic and epigenetic factors) and extrinsic factors (i.e., deriving from interaction of tumor cells with tumor microenvironment or other external factors). We reviewed mechanisms underlying PD-L1 expression regulation in order to provide a comprehensive overview and identify key regulatory factors that are or can potentially be exploited to improve outcomes on immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. Abstract Treatment with inhibition of programmed cell death 1 (PD-1) or its ligand (PD-L1) improves survival in advanced non-small-cell lung cancer (NSCLC). Nevertheless, only a subset of patients benefit from treatment and biomarkers of response to immunotherapy are lacking. Expression of PD-L1 on tumor cells is the primary clinically-available predictive factor of response to immune checkpoint inhibitors, and its relevance in cancer immunotherapy has fostered several studies to better characterize the mechanisms that regulate PD-L1 expression. However, the factors associated with PD-L1 expression are still not well understood. Genomic alterations that activate KRAS, EGFR, and ALK, as well as the loss of PTEN, have been associated with increased PD-L1 expression. In addition, PD-L1 expression is reported to be increased by amplification of CD274, and decreased by STK11 deficiency. Furthermore, PD-L1 expression can be modulated by either tumor extrinsic or intrinsic factors. Among extrinsic factors, the most prominent one is interferon-γ release by immune cells, while there are several tumor intrinsic factors such as activation of the mechanistic target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and Myc pathways that can increase PD-L1 expression. A deeper understanding of PD-L1 expression regulation is crucial for improving strategies that exploit inhibition of this immune checkpoint in the clinic, especially in NSCLC where it is central in the therapeutic algorithm. We reviewed current preclinical and clinical data about PD-L1 expression regulation in NSCLC.

Hematopoietic stem cell transplantation (HSCT) is the first-line immunotherapy to treat several hematologic disorders, although it can be associated with many complications reducing the survival rate, such as acute graft-versus-host disease (aGvHD) and infections. Given the fundamental role of the gut microbiome (GM) for host health, it is not surprising that a suboptimal path of GM recovery following HSCT may compromise immune homeostasis and/or increase the risk of opportunistic infections, with an ultimate impact in terms of aGvHD onset. Traditionally, the first nutritional approach in post-HSCT patients is parenteral nutrition (PN), which is associated with several clinical adverse effects, supporting enteral nutrition (EN) as a preferential alternative. The aim of the study was to evaluate the impact of EN vs. PN on the trajectory of compositional and functional GM recovery in pediatric patients undergoing HSCT. The GM structure and short-chain fatty acid (SCFA) production profiles were analyzed longitudinally in twenty pediatric patients receiving HSCT&mdash, of which, ten were fed post-transplant with EN and ten with total PN. According to our findings, we observed the prompt recovery of a structural and functional eubiotic GM layout post-HSCT only in EN subjects, thus possibly reducing the risk of systemic infections and GvHD onset.

Background Optimization of care to correct the unilateral cleft lip nasal deformity is hampered by lack of objective measures to quantify preoperative severity and outcome. The purpose of this study was to develop a consensus standard of nasal appearance using three-dimensional stereophotogrammetry; determine whether anthropometric measurements could be used to quantify severity and outcome; and determine whether preoperative severity predicts postoperative outcome. Methods The authors collected facial three-dimensional images of 100 subjects in three groups: 45 infants before cleft lip repair; the same 45 infants after cleft lip repair; and 45 children aged 8 to 10 years with previous repairs. Five additional age-matched unaffected control subjects were included in each group. Seven expert surgeons ranked images in each group according to nasal appearance. The rank sum score was used as consensus standard. Anthropometric analysis was performed on each image and compared to the rank sum score. Preoperative rank and anthropometric measurements were compared to postoperative rank. Results Interrater and intrarater reliability was excellent (intraclass correlation coefficient, >0.76; Pearson correlation, >0.75) on each of the three image sets. Columellar angle, nostril width ratio, and lateral lip height ratio were highly correlated with preoperative severity and moderately correlated with postoperative nasal appearance. Postoperative outcome was associated with preoperative severity (rank and anthropometric measurement). Conclusions Consensus ranking of preoperative severity and postoperative outcome can be achieved on three-dimensional images. Preoperative severity predicts postoperative outcomes. Columellar angle, nostril width ratio, and lateral lip height ratio are objective measures that correlate with consensus ratings by surgeons at multiple ages.

none 13 si Among other purposes, companies and regulatory agencies from around the world often adopt International Standard Organization (ISO) standards to determine acceptable practices, equipment and criteria for preventing occupational injuries and illnesses. ISO standards are based on a consensus among individuals who participate in the process. This discussion paper examines the scientific process for the development of several ISO standards on biomechanical factors, comparing it with processes used by other professional organizations, including scientific committees working on the development of clinical guidelines. While the ISO process has value, it also has clear limitations when it comes to developing occupational health and safety standards that should be based on scientific principles. open Armstrong, Tom J; Burdorf, Alex; Descatha, Alexis; Farioli, Andrea; Graf, Maggie; Horie, Seichi; Marras, William S; Potvin, Jim R; Rempel, David; Spatari, Giovanna; Takala, Esa-Pekka; Verbeek, Jos; Violante, Francesco S Armstrong, Tom J; Burdorf, Alex; Descatha, Alexis; Farioli, Andrea; Graf, Maggie; Horie, Seichi; Marras, William S; Potvin, Jim R; Rempel, David; Spatari, Giovanna; Takala, Esa-Pekka; Verbeek, Jos; Violante, Francesco S

Made available in DSpace on 2018-12-11T17:16:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Objectives The objective of the present study was to investigate the long-term effect of 0.01% acrolein (ACR) aqueous solution, employed as an additional primer, on the mechanical durability and enzymatic activity of resin-dentine interfaces created with a simplified etch-and-rinse adhesive. Methods Dentine surfaces were etched with 35% phosphoric acid for 15 s, rinsed and blot-dried. Specimens were then assigned to: Group 1: dentine pre-treated with 0.01% ACR aqueous solution for 1 min and bonded with Adper Scotchbond 1 XT (SB1XT), a 2-step etch-and-rinse adhesive; Group 2: SB1XT was applied on untreated acid-etched dentine (control). Resin composite build-ups were made using Filtek Z250. Microtensile bond strength was tested by stressing sectioned specimens to failure immediately or after 1 year of storage in artificial saliva at 37 °C. Zymography and in-situ zymography assays were performed for examining dentine matrix metalloproteinase (MMP) activities. Results The use of 0.01% ACR as conditioning primer appeared to have contributed better to preservation of bond strength over time without affecting immediate bond strength. Zymography and in-situ zymography showed reduction in MMP activities after the application of ACR. Conclusion Dentine collagen cross-linking produced by an ACR-based primer increases the longevity of resin-dentine bonds by reinforcement of the adhesive interface and reduction of dentine MMP activities. Further studies are required to evaluate the potential in vivo and in vivo cytotoxicity of ACR. Clinical significance The acrolein-based primer is a potentially useful clinical bonding tool because it demonstrates good collagen cross-linking ability within a clinically-acceptable working time. Although a low ACR concentration was employed in the present study, the cytotoxicity of ACR should be tested prior to clinical use. Department of Biomedical and Neuromotor Sciences DIBINEM University of Bologna - Alma Mater Studiorum School of Dentistry Faculty of Medicine University of Novi Sad Department of Restorative Dentistry School of Dentistry University of São Paulo Private Practice Department of Pediatric Dentistry and Orthodontics Araraquara School of Dentistry UNESP – University of Estadual Paulista The Dental College of Georgia Augusta University Department of Pediatric Dentistry and Orthodontics Araraquara School of Dentistry UNESP – University of Estadual Paulista

none 4 no Background Pelvic exenteration is the only radical treatment for locally advanced (ARC) or recurrent (RRC) rectal cancers. The long-term results of the procedure are variably reported in the literature, with recent series suggesting similar survival between ARC and RRC. The study aimed to analyze and compare the long-term survival and perioperative outcomes of patients undergoing pelvic exenteration for ARC and RRC in a tertiary center. Materials and methods This was a retrospective analysis of prospectively collected data. Comparison of variables was performed using Chi-square, Fisher's exact or Wilcoxon rank sum test as appropriate. The Kaplan Meier method was used to analyze the disease-free survival (DFS) and the log-rank test to compare the two groups. Results Since 2002, 46 patients underwent pelvic exenteration for ARC (28, 60.9%) and RRC (18, 39.1%). The groups had comparable characteristics, perioperative results, including postoperative complications, and rate of adjuvant chemotherapy. A R0 resection was obtained in 71.4% and 55.6% (p 0.41) and a T4 stage was diagnosed in 75% and 94.4% (p 0.22) of ARC and RRC patients, respectively. After a median follow-up time of 32.5 and 56.6 months (p 0.01), the 5-year DFS was significantly lower in the RRC group (23.6 vs 46.2%, p 0.006), even after exclusion of R1 cases (30 vs 54.5%, p 0.044). Conclusion The long-term disease free survival of patients undergoing pelvic exenteration is significantly worse when the procedure is performed for RRC, regardless of the tumor involvement of the resection margins. Rottoli, Matteo; Vallicelli, Carlo; Boschi, Luca; Poggioli, Gilberto Rottoli, Matteo; Vallicelli, Carlo; Boschi, Luca; Poggioli, Gilberto

none 11 no Several antipsychotics and antidepressants have been associated with QTc prolongation or other electrocardiogram (ECG) alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross-sectional sample n = 145 and prospective sample n = 68, naturalistic treatment) and a replication prospective sample (Clinical Antipsychotic Trials of Intervention Effectiveness, n = 515, randomized treatment) were analysed. In both prospective samples, baseline/follow-up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk. In the cross-sectional sample, ECG parameters were compared among drugs with different risk profile. The possible effect of single nucleotide polymorphisms (SNPs) in the CACNA1C gene on QTc was also investigated. There was no evidence of mean QTc prolongation or increased risk of clinically relevant QTc prolongation (≥20 msec.) in association with psychotropic drugs stratified according to their known cardiovascular risk. The prescription of drugs with cardiovascular risk was less common in older individuals or individuals with cardiovascular comorbidities. Other factors (gender, baseline QTc, renal function) affected QTc. rs1006737 and SNPs in linkage disequilibrium with it modulated QTc duration/changes in all samples. An association between risk drugs and shorter RR interval or higher heart rate was found in all samples. A relevant effect of psychotropic drugs with cardiovascular risk on QTc duration was not observed. A number of factors other than psychotropic drugs may influence QTc. CACNA1C rs1006737 may modulate QTc in patients treated with psychotropic drugs. none Fabbri, Chiara; Boriani, Giuseppe; Diemberger, Igor; Filippi, Maria Giulia; Ravegnini, Gloria; Hrelia, Patrizia; Minarini, Alessandro; Albani, Diego; Forloni, Gianluigi; Angelini, Sabrina; Serretti, Alessandro Fabbri, Chiara; Boriani, Giuseppe; Diemberger, Igor; Filippi, Maria Giulia; Ravegnini, Gloria; Hrelia, Patrizia; Minarini, Alessandro; Albani, Diego; Forloni, Gianluigi; Angelini, Sabrina; Serretti, Alessandro

none 55 si First published: 22 December 2016 Background: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. Aim: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. Methods: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH. Results: Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres. Conclusions: There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis. mixed R. Liberal; Y. S. de Boer; R. J. Andrade; G. Bouma; G. N. Dalekos; A. Floreani; D. Gleeson; G. M. Hirschfield; P. Invernizzi; M. Lenzi; A. W. Lohse; G. Macedo; P. Milkiewicz; B. Terziroli; B. van Hoek; J. M. Vierling; M. A. Heneghan; on behalf of the International Autoimmune Hepatitis Group (IAIHG); A. Pares; A. J. Montano-Loza; A. Granito; A. E. Kremer; A. Floreani; A. W. Lohse; B. van Hoek; B. Terziroli; C. Schramm; C. Lammert; E. L. R. Cancado; E. Bjornsson; F. Lammert; G. N. Dalekos; G. Bouma; G. M. Hirschflield; G. Macedo; H. Hofer; I. Mackay; J. Neuberger; J. M. Vierling; J.P.H. Drenth; C.M.J. van Nieuwkerk; L. Muratori; M. Lenzi; M. Swain; M. Heneghan; M. Zeniya; O. Chazouilleres; P. Gines; P. Invernizzi; P. Milkiewicz; R. J. Andrade; R. Chapman; T. Berg; H. van Buuren; X. Ma R. Liberal; Y. S. de Boer; R. J. Andrade; G. Bouma; G. N. Dalekos; A. Floreani; D. Gleeson; G. M. Hirschfield; P. Invernizzi; M. Lenzi; A. W. Lohse; G. Macedo; P. Milkiewicz; B. Terziroli; B. van Hoek; J. M. Vierling; M. A. Heneghan; on behalf of the International Autoimmune Hepatitis Group (IAIHG); A. Pares; A. J. Montano-Loza; A. Granito; A. E. Kremer; A. Floreani; A. W. Lohse; B. van Hoek; B. Terziroli; C. Schramm; C. Lammert; E. L. R. Cancado; E. Bjornsson; F. Lammert; G. N. Dalekos; G. Bouma; G. M. Hirschflield; G. Macedo; H. Hofer; I. Mackay; J. Neuberger; J. M. Vierling; J.P.H. Drenth; C.M.J. van Nieuwkerk; L. Muratori; M. Lenzi; M. Swain; M. Heneghan; M. Zeniya; O. Chazouilleres; P. Gines; P. Invernizzi; P. Milkiewicz; R. J. Andrade; R. Chapman; T. Berg; H. van Buuren; X. Ma

none 9 no Atherosclerosis is considered to be a T-cell-driven disease since the interaction between resident cells, immune cells and their products has been recognized to promote the development of atheromatous plaques in the arterial walls [1]. The process of atherosclerosis evolves from a prelesional phase, which is potentially reversible, to complicated lesions characterized by the formation of a fibrous cap and vulnerable plaques, followed by possible rupture and atherothrombosis. none Gelsomino, F.; Fiorentino, M.*; Zompatori, M.; Poerio, A.; Melotti, B.; Sperandi, F.; Gargiulo, M.; Borghi, C.; Ardizzoni, A. Gelsomino, F.; Fiorentino, M.*; Zompatori, M.; Poerio, A.; Melotti, B.; Sperandi, F.; Gargiulo, M.; Borghi, C.; Ardizzoni, A.

Background & Aims Nosocomial acute-on-chronic liver failure (nACLF) develops in at least 10% of patients with cirrhosis hospitalized for acute decompensation (AD), greatly worsening their prognosis. In this prospective observational study, we aimed to identify rapidly obtainable predictors at admission, which allow for the early recognition and stratification of patients at risk of nACLF. Methods A total of 516 consecutive patients hospitalized for AD of cirrhosis were screened: those who did not present ACLF at admission (410) were enrolled and surveilled for the development of nACLF. Results Fifty-nine (14%) patients developed nALCF after a median of 7 (IQR 4–18) days. At admission, they presented a more severe disease and higher degrees of systemic inflammation and anemia than those (351; 86%) who remained free from nACLF. Competing risk multivariable regression analysis showed that baseline MELD score (sub-distribution hazard ratio [sHR] 1.15; 95% CI 1.10–1.21; p ≪0.001), hemoglobin level (sHR 0.81; 95% CI 0.68–0.96; p = 0.018), and leukocyte count (sHR 1.11; 95% CI 1.06–1.16; p ≪0.001) independently predicted nACLF. Their optimal cut-off points, determined by receiver-operating characteristic curve analysis, were: 13 points for MELD score, 9.8 g/dl for hemoglobin, and 5.6x109/L for leukocyte count. These thresholds were used to stratify patients according to the cumulative incidence of nACLF, being 0, 6, 21 and 59% in the presence of 0, 1, 2 or 3 risk factors (p ≪0.001). Nosocomial bacterial infections only increased the probability of developing nACLF in patients with at least 1 risk factor, rising from 3% to 29%, 16% to 50% and 52% to 83% in patients with 1, 2 or 3 risk factors, respectively. Conclusions Easily available laboratory parameters, related to disease severity, systemic inflammation, and anemia, can be used to identify, at admission, hospitalized patients with AD at increased risk of developing nACLF. Lay summary More than 10% of patients with cirrhosis hospitalized because of an acute decompensation develop acute-on-chronic liver failure, which is associated with high short-term mortality, during their hospital stay. We found that the combination of 3 easily obtainable variables (model for end-stage liver disease score, leukocyte count and hemoglobin level) help to identify and stratify patients according to their risk of developing nosocomial acute-on-chronic liver failure, from nil to 59%. Moreover, if a nosocomial bacterial infection occurs, such an incidence proportionally increases from nil to 83%. This simple approach helps to identify patients at risk of developing nosocomial acute-on-chronic liver failure at admission to hospital, enabling clinicians to put in place preventive measures., Graphical Abstract Unlabelled Image, Highlights • ACLF complicates more than 10% of hospitalizations for acute decompensation of cirrhosis. • Easily available predictors of nosocomial ACLF are fundamental to implement appropriate preventive strategies. • MELD score, leucocyte count and hemoglobin can stratify patients according to their risk of developing nosocomial ACLF. • Further studies are required to validate these results and provide additional insights.

none 13 no Published Online First: 12 September 2016 OBJECTIVE: The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. DESIGN: Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1H nuclear magnetic resonance. RESULTS: Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. CONCLUSIONS: Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide

none 32 BACKGROUND Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease. METHODS In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level. RESULTS Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P

none 12 no Study Design. Retrospective case series. Objective. To report on the natural history and long-term outcome of a large series of consecutive primary sacral chordoma patients surgically treated at two reference centers. Summary of Background Data. Sacral chordomas are rare tumors with poor long-term prognosis mainly caused by local failure. Till date, a few large series with long follow up are available in literature. Methods. All consecutive patients affected by primary localized sacral chordoma operated on at two Italian reference centers between 1981 and 2012 were included. Overall survival (OS), disease free survival (DFS), crude cumulative incidence (CCI) of local recurrence (LR), and distant metastases (DM) were calculated. Multivariable analyses for OS, DFS, LR, and DM were performed. Results. A total of 99 patients were identified: 65 males and 34 females. Median age was 59 years (range 22-77 yrs), median tumor size was 9cm (range 4-22). Nineteen patients received pre- or postoperative radiotherapy (RT). Wide (R0) surgical margins were achieved in 46 patients, marginal (R1) margins in 43 patients and intralesional (R2) margins in 10 patients. At a median follow up of 8.7 years (range 1-23.8 yrs) 30 patients died of disease, 31 patients developed local relapse, 16 patients developed distant metastasis, whereas 51 patients are alive without disease. OS and DFS at 5, 10, and 15 year were 92% and 63%, 45% and 62%, 36% and 21%, respectively, without any evidence of a plateau in the curves.CCI of LR and DM were 30% and 9% at 5 years, 46% and 18% at 10 years, 56% and 23% at 15 years. Size of the tumor and quality of surgical margins were the only significant predictors of long-term outcome. DFS for 15 years was, in fact, 49% for R0 and 7% for R1, respectively. Conclusion. In this series, long-term outcome of resected sacral chordoma was poor, with less than 25% patients were disease-free at 15 years. Interestingly, only half of the patients treated with R0 resection had no evidence of recurrence at 15 years. When surgical margins are expected to be positive other treatment modalities should be considered, especially when expected sequelae are substantial as in the case of more cephalad levels of resection. Level of Evidence: 3 Radaelli, Stefano; Stacchiotti, Silvia; Ruggieri, Pietro; Donati, Davide; Casali, Paolo G.; Palmerini, Emanuela; Collini, Paola; Gambarotti, Marco; Porcu, Luca; Boriani, Stefano; Gronchi, Alessandro; Picci, Piero Radaelli, Stefano; Stacchiotti, Silvia; Ruggieri, Pietro; Donati, Davide; Casali, Paolo G.; Palmerini, Emanuela; Collini, Paola; Gambarotti, Marco; Porcu, Luca; Boriani, Stefano; Gronchi, Alessandro; Picci, Piero

none 9 no Objective The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%)

none 3 no tObjective. Root canal filling sealers based on polymethyl hydrogensiloxane or poly-methyl hydrogensiloxane-guttapercha – introduced to improve the quality of conventionalguttapercha-based and resin-based systems – showed advantages in handiness and clinicalapplication.The aim of the study was to evaluate the chemical–physical properties of a novelpolysiloxane-guttapercha calcium silicate-containing root canal sealer (GuttaFlow bioseal).Methods. GuttaFlow bioseal was examined and compared with GuttaFlow2, RoekoSeal andMTA Fillapex sealers. Setting times, open and impervious porosity and apparent porosity,water sorption, weight loss, calcium release, and alkalinizing activity were evaluated. ESEM-EDX-Raman analyses of fresh materials and after soaking in simulated body fluid were alsoperformed.Results. Marked differences were obtained among the materials.GuttaFlow bioseal showed low solubility and porosity, high water sorption, moderatecalcium release and good alkalinizing activity. MTA Fillapex showed the highest calciumrelease, alkalinizing activity and solubility, RoekoSeal the lowest calcium release, no alkalin-izing activity, very low solubility and water sorption. Only GuttaFlow bioseal showed apatiteforming ability.Significance. GuttaFlow bioseal showed alkalinizing activity together with negligible sol-ubility and slight calcium release. Therefore, the notable nucleation of apatite and apatiteprecursors can be related to the co-operation of CaSi particles (Si OH groups) with polysilox-ane (Si O Si groups).The incorporation of a calcium silicate component into polydimethyl polymethylhydro-gensiloxane guttapercha sealers may represent an attractive strategy to obtain a bioactivebiointeractive flowable guttapercha sealer for moist/bleeding apices with bone defects inendodontic therapy. M.G. Gandolfi; F. Siboni; C. Prati M.G. Gandolfi; F. Siboni; C. Prati

To evaluate the potential role of contrast harmonic endoscopic ultrasound (CH-EUS) in the differential diagnosis of pancreatic cysts and detection of malignancy.Patients who underwent CH-EUS for evaluation of cyst wall, septae, and solid components of pancreatic cysts were included. The findings were compared to fine needle aspiration and surgery.Seventy-six patients were included. Serous and mucinous cysts were both hyperenhanced (86% and 89%, respectively; P = ns), whereas pseudocysts were hypoenhanced in 90% of the cases (P = 0.000004 vs serous cysts and P = 0.000005 vs mucinous cysts). Patients showing hyperenhanced solid components were finally diagnosed with malignancy (2 malignant intraductal papillary mucinous neoplasms, 2 cystic neuroendocrine tumors), in contrast to the patients with nonenhanced solid components who resulted to have either benign cysts with internal mucus clots (n = 10) or pseudocysts with internal debris (n = 8).CH-EUS allowed differentiation between pseudocysts and other pancreatic cysts but not mucinous versus serous cysts. Malignant vegetations inside pancreatic cystic lesions were clearly shown by CH-EUS as solid components with features of hyperenhancement, directing EUS-fine needle aspiration of potential neoplastic areas and avoiding puncture of debris and mucus plugs.

none 11 no BACKGROUND: Experts and scientific society guidelines recommend that rapid on-site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni

open 17 no We thank Rita Bertoni and Antonella Orlando for the technical assistance. This work has been supported by Bologna AIL (Italian Association against Leukemia, Lymphoma and Myeloma), Roberto and Cornelia Pallotti Legacy for Cancer Research (University of Bologna) to M.B., and REUSE with Love ONLUS, Bologna, Italy. Umbilical Cord Blood (UCB) represents a valid option for patients with hematopoietic malignancies lacking an HLA matched donor. To overcome the limitation of the low stem cell dose of UCB, the intrabone (IB) route has been proposed. We report the results of a prospective study on a poor-prognosis cohort of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 ± 9% (ANC > 0.5 × 109/L) and 70 ± 10% (platelet > 50 × 109/L) and correlated with CD34 + cells in the graft. NRM was 20 ± 9%. No severe aGVHD and only one extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis that the direct IB injection could affect the expression of stem cells regulatory pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl in CD34 + cells at day + 10 significantly correlated with hematological recovery. In conclusion, IB-UCB transplant success is associated with low incidence of GVHD and high-speed platelet recovery; intrabone route may preserve full hematopoietic stemness by direct delivery of UCB stem cells into the hypoxic HSC niche. none none Bonifazi, Francesca; Dan, Elisa; Labopin, Myriam; Sessa, Mariarosaria; Guadagnuolo, Viviana; Ferioli, Martina; Rizzi, Simonetta; De Carolis, Sabrina; Sinigaglia, Barbara; Motta, Maria Rosa; Bontadini, Andrea; Giudice, Valeria; Martinelli, Giovanni; Arpinati, Mario; Cavo, Michele; Bonafé, Massimiliano; Storci, Gianluca Bonifazi, Francesca; Dan, Elisa; Labopin, Myriam; Sessa, Mariarosaria; Guadagnuolo, Viviana; Ferioli, Martina; Rizzi, Simonetta; De Carolis, Sabrina; Sinigaglia, Barbara; Motta, Maria Rosa; Bontadini, Andrea; Giudice, Valeria; Martinelli, Giovanni; Arpinati, Mario; Cavo, Michele; Bonafé, Massimiliano; Storci, Gianluca

none 17 no Prosthetic joint infection (PJI) is among the most-severe complications of a total joint arthroplasty. Identification of the causal organism is of paramount importance for successful treatment, and sonication of implants may aid in this identification. Dithiothreitol (DTT) treatment has been proposed as an alternative to sonication to improve diagnosis, reduce costs, and improve reliability of the procedure, but its efficacy remains poorly characterized. mixed Sambri, Andrea; Cadossi, Matteo; Giannini, Sandro; Pignatti, Giovanni; Marcacci, Maurilio; Neri, Maria Pia; Maso, Alessandra; Storni, Elisa; Gamberini, Simonetta; Naldi, Susanna; Torri, Arianna; Zannoli, Silvia; Tassinari, Martina; Fantini, Michela; Bianchi, Giuseppe; Donati, Davide; Sambri, Vittorio Sambri, Andrea; Cadossi, Matteo; Giannini, Sandro; Pignatti, Giovanni; Marcacci, Maurilio; Neri, Maria Pia; Maso, Alessandra; Storni, Elisa; Gamberini, Simonetta; Naldi, Susanna; Torri, Arianna; Zannoli, Silvia; Tassinari, Martina; Fantini, Michela; Bianchi, Giuseppe; Donati, Davide; Sambri, Vittorio

Summary: Background: We studied prevalence of chronic pain, related or not to cancer, in elderly patients, its correlation with socio-clinical factors, and its effects on daily living, to estimate feasibility of an early assessment of palliative care needs in a non-specialist hospital setting. Methods: In this prospective study, a questionnaire concerning pain and multidimensional assessment tools were administered to patients consecutively admitted to a Department of Internal Medicine comprising a Stroke Unit. Results: One hundred patients were recruited, 38 of whom experiencing pain, chronic in 26 patients (68%). A total of 34.3% of patients with pain and 12.5% of patients without pain suffered from depression (P = 0.013). Depressed patients showed significantly higher median values in all Brief Pain Inventory (BPI) scores and items. Depressed patients also obtained less pain relief from therapies. Patients with mild dementia showed, significantly or as a trend, a higher median least, average and “pain right now” pain values. Worst pain values in the previous 24 h increased with age. Only 42% of patients reported to be on pain therapy upon admission to hospital, whereas 62% were undergoing treatment at the time of discharge. A correlation was found between the pain value and the level of interference with daily activities. Pain was mentioned in the discharge letter in 36% of cases. Conclusion: Pain is a critical underestimated problem in elderly patients. A timely systematic evaluation of the pain would call attention to palliative care needs and reduce the negative effects of uncontrolled pain on the quality of life. Keywords: Pain assessment, Pain prevalence, Elderly patients, Pain and depression, Pain and activities of daily living

none 6 no Abstract OBJECTIVES: A relatively neglected aspect of cleft lip nasal deformity is the effect of septal deviation and inferior turbinate hypertrophy (ITH) on the functional airway. In particular, ITH in the noncleft side can be especially problematic, because it reduces the healthy nasal area, creating bilateral nasal obstruction that might affect the growth of the maxillofacial skeleton. Although these anatomic and functional changes are documented, few recommendations have been developed regarding the proper approach to ITH. The aim of the present study was to asses the ITH severity and determine the degree of nasal airway patency in patients who have undergone primary correction of the nasal septum during lip repair compared to patients operated on without primary septal correction. METHODS: The study population included two groups. One group consisted of twenty unilateral cleft lip palate UCLP patients who have previously undergone primary rhinoseptoplasty as part of their treatment plan. The control group consisted of twenty UCLP patients operated on without rhinoseptal correction. The Nasal Obstructive Symptom Evaluation (NOSE) scale and nasal endoscopy were used to assess nasal obstruction. RESULTS: The overall untreated group reported severe symptoms across all NOSE scale dimensions more frequently than children who have undergone primary rhinoseptoplasty. The difference was statistically significant for each dimensions (p

none 13 no Fondazione Luisa Fanti Melloni” , University of Bologna, Italy Background: The aim was to assess the long-term outcome of patients diagnosed with type A and type B acute aortic syndromes (AAS) and the mortality risk predictors. Methods: A single centre retrospective observational study was performed on consecutive patients diagnosed with AAS and discharged between 2000 and 2016: 242 surgically treated type A, 87 uncomplicated, medically treated type B, and 80 complicated type B who received endovascular/surgical/hybrid treatment. Follow up of discharged patients (5 ± 3.9 years) was almost complete by the end of the study (December 2017). Results: The mean age was 65.3 ± 12.5 years, and 70.2% were men. Long-term all cause mortality was 5.4 per 100 patients per year in surgically treated type A AAS patients and 6.7 per 100 patients per year in type B AAS patients (p =.236). The rates of major aorta related events were 6.1 per 100 patients per year and 13.4 per 100 patients per year, respectively (p

none 14 no Aim: To identify patients with recurrent glioblastoma after temozolomide (TMZ) concurrent with and adjuvant to radiotherapy who could benefit from TMZ rechallenge at the time of disease progression. Methods: We retrospectively evaluated 106 glioblastoma patients who had nonprogressive disease at first magnetic resonance imaging after completion of TMZ concurrent with and adjuvant to radiotherapy, a treatment-free interval (TFI) of at least 8 weeks and received TMZ rechallenge or a nitrosourea at the time of progression. Results: In patients with TFI ≥5 months, median survival was 17.7 and 11.6 months and median progression-free survival was 8.1 and 5.8 months in the TMZ and nitrosourea group, respectively. Longer TFI was associated with reduced risk for death (p = 0.002) and for disease progression (p = 0.005). Conclusion: TFI ≥5 months represents a predictor of retained TMZ sensitivity. none Franceschi, Enrico; Lamberti, Giuseppe; Visani, Michela; Paccapelo, Alexandro; Mura, Antonella; Tallini, Giovanni; Pession, Annalisa; De Biase, Dario; Minichillo, Santino; Tosoni, Alicia; Di Battista, Monica; Cubeddu, Alessio; Bartolini, Stefania; Brandes, Alba A* Franceschi, Enrico; Lamberti, Giuseppe; Visani, Michela; Paccapelo, Alexandro; Mura, Antonella; Tallini, Giovanni; Pession, Annalisa; De Biase, Dario; Minichillo, Santino; Tosoni, Alicia; Di Battista, Monica; Cubeddu, Alessio; Bartolini, Stefania; Brandes, Alba A*

Objective Hepatitis B virus infection is a relevant health problem with more than 400 million infected people worldwide. Our aim was to analyze quality of life of hepatitis B virus surface antigen-positive patients in inactive status or treated with antivirals. Patients and methods Patients referred to our center between February and October 2016 were prospectively enrolled. Half-structured interview was used for examining psychological symptoms and Illness Behavior Questionnaire for exploring attitudes toward illness. We used World Health Organization Quality of Life-short version survey for studying quality of life and logistic regression to find possible predictors of nonadequate quality of life. Results The study involved 102 patients. At Illness Behavior Questionnaire test, psychological perception of illness (21.6%), and denial of illness itself (13.7%) were the most frequent conditions. Inactive and treated subgroups were comparable for almost all variables and scores, but patients on treatment were significantly more often male, older, and cirrhotic. Sleep disturbance emerged as an independent predictor of inadequate quality of life in Physical health, anxiety in Social relationship, and both anxiety and hostility in Environmental health domain. Conclusion Inactive carriers and patients on treatment showed the same global quality of life, but the second group was older and more frequently with an advanced liver disease. Further studies might specifically evaluate the impact of antiviral therapy on quality of life.

none 9 no Objective: To test the hypothesis that allergic proctocolitis, a cause of self-limiting rectal bleeding in infants, can predispose to the development of functional gastrointestinal disorders (FGIDs) later in childhood. Study design: We studied a cohort of 80 consecutive patients diagnosed with allergic proctocolitis. Their sibling or matched children presenting to the same hospital for minor trauma served as controls. Parents of the patients with allergic proctocolitis and controls participated in a telephone interview every 12 months until the child was at least 4 years old. At that time, they were asked to complete the parental Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III version. Results: Sixteen of the 160 subjects (10.0%) included in the study met the Rome III criteria for FGIDs. Among the 80 patients with allergic proctocolitis, 12 (15.0%) reported FGIDs, compared with 4 of 80 (5.0%) controls (P = .035). After adjustment for age and sex, the OR for FGIDs in allergic proctocolitis group was 4.39 (95% CI, 1.03-18.68). FGIDs were significantly associated with iron deficiency anemia, duration of hematochezia, and younger age at presentation. In a multivariate analysis, only the duration of hematochezia was significantly associated with the development of FGIDs (OR, 3.14; 95% CI,1.72-5.74). Conclusions: We have identified allergic proctocolitis as a new risk factor for the development of FGIDs in children. Our data suggest that not only infection, but also a transient early-life allergic inflammatory trigger may induce persistent digestive symptoms, supporting the existence of "postinflammatory" FGIDs. open Di Nardo, Giovanni; Cremon, Cesare; Frediani, Simone; Lucarelli, Sandra; Villa, Maria Pia; Stanghellini, Vincenzo; La Torre, Giuseppe; Martemucci, Luigi; Barbara, Giovanni* Di Nardo, Giovanni; Cremon, Cesare; Frediani, Simone; Lucarelli, Sandra; Villa, Maria Pia; Stanghellini, Vincenzo; La Torre, Giuseppe; Martemucci, Luigi; Barbara, Giovanni*

Introduction. Host lipid metabolism influences viral replication and lifecycle of hepatitis C virus. Our aim was to evaluate changes in glucose and lipid metabolism of patients with chronic hepatitis C after therapy with direct acting antivirals (DAA).Material and methods. We considered patients consecutively treated between January and November 2015 recording clinical data at baseline and week 24 of follow-up. Frozen serum samples were used for apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)]. Wilcoxon test was utilized to estimate trends and Logistic Regression for predictors of lipid changes.Results. We enrolled 100 patients, mostly cirrhotic (81%) and with genotype 1b (59%). Ninety-three patients achieved sustained virological response (SVR), while 7 relapsed. Homeostasis model assessment of insulin resistance declined (from 3 to 2.7, p < 0.001); non-high density lipoprotein (HDL) cholesterol increased from 102 ± 29 to 116 ± 35 (p < 0.001), and Lp(a) from 5.6 ± 6.5 to 9.8 ± 11.5 mg/dL (p < 0.001). Rise of low-density lipoprotein/HDL and apoB/apoA1 ratio were registered (from 1.79 ± 1.10 to 2.08 ± 1.05 and from 0.48 ± 0.18 to 0.53 ± 0.18 mg/dL, p < 0.001). We conducted a subanalysis on patients with relapse. In this subgroup, no change of lipid profile was recorded. At multivariate analysis emerged that the addition of ribavirin to DAA, represented an independent predictor of increased Lp(a) (OR 3.982, 95% CI 1.206-13.144, p = 0.023).Conclusion. DAA therapy led to reduction of insulin resistance. In contrast, pro-atherogenic lipid changes were observed in patients with SVR. Further studies will be necessary to evaluate the cardiovascular balance between amelioration of glucose metabolism and negative changes of lipid profile.

none 98 no The SIM‐AF study was funded by a competitive grant from Bristol Myers Squibb/Pfizer Alliance, within the European Thrombosis Investigator‐Initiated Research Program (ERISTA) (Grant N° BMS ISR #CV 185‐483) Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N=221), errors in the prescribed doses were the most frequent cause of inappropriate use (N=55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population. none Franchi, Carlotta*; Antoniazzi, Stefania; Proietti, Marco; Nobili, Alessandro; Mannucci, Pier Mannuccio; Santalucia, Paola; Monzani, Valter; Marcucci, Maura; Antoniazzi, Stefania; Bosari, Silvano; Mannucci, Pier Mannuccio; Franchi, Carlotta; Brignolo, Barbara; Proietti, Marco; Nicolis, Enrico; Ardoino, Ilaria; Fenoglio, Luigi M.; Melchio, Remo; Fabris, Fabrizio; Sartori, Maria Teresa; Manfredini, Roberto; De Giorgi, Alfredo; Fabbian, Fabio; Biolo, Gianni; Zanetti, Michela; Altamura, Nicola; Sabbà, Carlo; Suppressa, Patrizia; Bandiera, Francesco; Usai, Carlo; Murialdo, Giovanni; Fezza, Francesca; Marra, Alessio; Castelli, Francesca; Cattaneo, Federico; Beccati, Valentina; di Minno, Giovanni; Tufano, Antonella; Contaldi, Paola; Lupattelli, Graziana; Bianconi, Vanessa; Cappellini, Domenica; Hu, Cinzia; Minonzio, Francesca; Fargion, Silvia; Burdick, Larry; Francione, Paolo; Peyvandi, Flora; Rossio, Raffaella; Colombo, Giulia; Ceriani, Giuliana; Lucchi, Tiziano; Manfellotto, Dario; Caridi, Irene; Corazza, Gino Roberto; Miceli, Emanuela; Padula, Donatella; Fraternale, Giacomo; Guasti, Luigina; Squizzato, Alessandro; Maresca, Andrea; Liberato, Nicola Lucio; Tognin, Tiziana; Rozzini, Renzo; Bellucci, Francesco Baffa; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Dore, Maurizio; Mete, Francesca; Gino, Miriam; Franceschi, Francesco; Gabrielli, Maurizio; Perticone, Francesco; Perticone, Maria; Bertolotti, Marco; Mussi, Chiara; Borghi, Claudio; Strocchi, Enrico; Durazzo, Marilena; Fornengo, Paolo; Dallegri, Franco; Ottonello, Luciano Carlo; Salam, Kassem; Caserza, Lara; Barbagallo, Mario; Di Bella, Giovanna; Annoni, Giorgio; Bruni, Adriana Antonella; Odetti, Patrizio; Nencioni, Alessio; Monacelli, Fiammetta; Napolitano, Armando; Brucato, Antonio; Valenti, Anna; Castellino, Pietro; Zanoli, Luca; Mazzeo, Marco Franchi, Carlotta*; Antoniazzi, Stefania; Proietti, Marco; Nobili, Alessandro; Mannucci, Pier Mannuccio; Santalucia, Paola; Monzani, Valter; Marcucci, Maura; Antoniazzi, Stefania; Bosari, Silvano; Mannucci, Pier Mannuccio; Franchi, Carlotta; Brignolo, Barbara; Proietti, Marco; Nicolis, Enrico; Ardoino, Ilaria; Fenoglio, Luigi M.; Melchio, Remo; Fabris, Fabrizio; Sartori, Maria Teresa; Manfredini, Roberto; De Giorgi, Alfredo; Fabbian, Fabio; Biolo, Gianni; Zanetti, Michela; Altamura, Nicola; Sabbà, Carlo; Suppressa, Patrizia; Bandiera, Francesco; Usai, Carlo; Murialdo, Giovanni; Fezza, Francesca; Marra, Alessio; Castelli, Francesca; Cattaneo, Federico; Beccati, Valentina; di Minno, Giovanni; Tufano, Antonella; Contaldi, Paola; Lupattelli, Graziana; Bianconi, Vanessa; Cappellini, Domenica; Hu, Cinzia; Minonzio, Francesca; Fargion, Silvia; Burdick, Larry; Francione, Paolo; Peyvandi, Flora; Rossio, Raffaella; Colombo, Giulia; Ceriani, Giuliana; Lucchi, Tiziano; Manfellotto, Dario; Caridi, Irene; Corazza, Gino Roberto; Miceli, Emanuela; Padula, Donatella; Fraternale, Giacomo; Guasti, Luigina; Squizzato, Alessandro; Maresca, Andrea; Liberato, Nicola Lucio; Tognin, Tiziana; Rozzini, Renzo; Bellucci, Francesco Baffa; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Dore, Maurizio; Mete, Francesca; Gino, Miriam; Franceschi, Francesco; Gabrielli, Maurizio; Perticone, Francesco; Perticone, Maria; Bertolotti, Marco; Mussi, Chiara; Borghi, Claudio; Strocchi, Enrico; Durazzo, Marilena; Fornengo, Paolo; Dallegri, Franco; Ottonello, Luciano Carlo; Salam, Kassem; Caserza, Lara; Barbagallo, Mario; Di Bella, Giovanna; Annoni, Giorgio; Bruni, Adriana Antonella; Odetti, Patrizio; Nencioni, Alessio; Monacelli, Fiammetta; Napolitano, Armando; Brucato, Antonio; Valenti, Anna; Castellino, Pietro; Zanoli, Luca; Mazzeo, Marco

none 12 no Programma di ricerca Regione-Università, RegioneEmilia-Romagna2010-2012 — Area1Innovativeresearch.Title: Technological innovations in the treatment of heart failure ” Objectives: To compare the effectiveness and safety of balloon aortic valvuloplasty (BAV) performed with or without rapid ventricular pacing (RP). Background: BAV technique is poorly standardized. Methods: One hundred consecutive patients were randomly assigned 1:1 between BAV performed with or without RP. Exclusion criteria were an immediate indication for surgical or transcatheter aortic valve replacement, presentation in cardiogenic shock or pulmonary edema refractory to medical stabilization. Results: There were 51 patients in the BAV group performed with RP, 49 in the BAV group without RP (noRP). Procedural success (50% hemodynamic gradient reduction) was achieved in 37.3% and 55.1%, respectively (P=0.16). Fewer people in the noRP group complained of poor tolerance to the procedure (16% vs 41%). The primary efficacy endpoint, a 50% reduction in the mean echocardiographic trans-aortic gradient, was met in 21/49 patients in the noRP group compared to 20/51 in the RP (42.9% vs 39.2%; P=0.84). No significant difference between the groups was observed in the primary safety endpoint, a 30-day composite of death, myocardial infarction, stroke, acute aortic regurgitation, and BARC bleeding ≥3 (8.2% noRP vs 13.7%; P=0.53). The noRP group required fewer bailout temporary pacemakers (P=0.048) and had a lower incidence of moderate/severe renal function worsening (4.1% vs 17.6%; P=0.052). Conclusions: Rapid ventricular pacing did not influence BAV efficacy or safety and tolerance was slightly worse. none Dall'Ara, Gianni; Marzocchi, Antonio; Taglieri, Nevio; Moretti, Carolina; Rodinò², Giulio; Chiarabelli, Matteo; Bottoni, Paolo; Marrozzini, Cinzia; Sabattini, Maria Rita; Bacchi-Reggiani, Maria-Letizia; Rapezzi, Claudio; Saia, Francesco Dall'Ara, Gianni; Marzocchi, Antonio; Taglieri, Nevio; Moretti, Carolina; Rodinò², Giulio; Chiarabelli, Matteo; Bottoni, Paolo; Marrozzini, Cinzia; Sabattini, Maria Rita; Bacchi-Reggiani, Maria-Letizia; Rapezzi, Claudio; Saia, Francesco

open 9 no The incidence of pancreatic cancer is increasing. Most patients have advanced disease at diagnosis, and therapeutics is limited in this setting. Gemcitabine and nab-paclitaxel combination is indicated as first-line treatment in patients with metastatic cancer of pancreas. The most common adverse events of Grade 3 or higher gemcitabine and nab-paclitaxel combination are neutropenia, fatigue and neuropathy. In this report, we describe a rare case of organizing pneu- monia associated with the use of nab-paclitaxel and gemcitabine in metastatic pancreatic cancer. A 68-year-old female underwent total splenopancreatectomy for ductal adenocarcinoma of the neck of the pancreas, followed by adjuvant chemoradiation therapy. Afterwards she relapsed and received first-line chemotherapy with gemcitabine plus nab-pa- clitaxel combination for 12 cycles. Following the administration of the 12th cycle of gemcitabine plus nab-paclitaxel, the patient experienced low-grade pyrexia, effort dyspnoea, persistent non-productive cough and malaise. High-resolution CT scan of chest revealed new-onset bilateral peripheral ground-glass opacities, smooth interlobular septal thickening and patchy subpleural consolidation areas, findings consistent with organizing pneumonia. A thorough microbiological workup was negative. Treatment with steroids resulted in prompt clinical and radiological improvement. Organizing pneumonia closely mimics infection or progressive disease and can be difficult to diagnose in the setting of malignancy. Correct diagnosis is of primary importance since delay in treatment can result in significantly adverse patient outcomes. open FRANCESCA COMITO, ELISA GRASSI, ANTONIO POERIO, EVA FREIER, LUCIA CALCULLI, MAURIZIO ZOMPATORI, CLAUDIO RICCI, RICCARDO CASADEI, MARIACRISTINA DI MARCO FRANCESCA COMITO, ELISA GRASSI, ANTONIO POERIO, EVA FREIER, LUCIA CALCULLI, MAURIZIO ZOMPATORI, CLAUDIO RICCI, RICCARDO CASADEI, MARIACRISTINA DI MARCO

none 10 si Background & Aims: Recently, Baveno VI guidelines suggested that esophagogastroduodenoscopy (EGD) can be avoided in patients with compensated advanced chronic liver disease (cACLD) who have a liver stiffness measurement (LSM) 150,000/mm3. We aimed to: assess the performance of spleen stiffness measurement (SSM) in ruling out patients with high-risk varices (HRV); validate Baveno VI criteria in a large population and assess how the sequential use of Baveno VI criteria and SSM could safely avoid the need for endoscopy. Methods: We retrospectively analyzed 498 patients with cACLD who had undergone LSM/SSM by transient elastography (TE) (FibroScan®), platelet count and EGDs from 2012 to 2016 referred to our tertiary centre. The new combined model was validated internally by a split-validation method, and externally in a prospective multicentre cohort of 115 patients. Results: SSM, LSM, platelet count and Child-Pugh-B were independent predictors of HRV. Applying the newly identified SSM cut-off (≤46 kPa) or Baveno VI criteria, 35.8% and 21.7% of patients in the internal validation cohort could have avoided EGD, with only 2% of HRVs being missed with either model. The combination of SSM with Baveno VI criteria would have avoided an additional 22.5% of EGDs, reaching a final value of 43.8% spared EGDs, with

none 11 no Objectives: To investigate the impact of treatment duration on mortality and on relapse in patients with Escherichia coli bloodstream infection (BSI). Methods: Retrospective single-centre study of patients diagnosed with E. coli BSI at our centre over a 4-year period. Exclusion criteria: age 10 days) therapy. Primary end point was all-cause mortality within 90 days after index BSI. Secondary end point was relapse, defined as repeat isolation of E. coli from blood cultures within 90 days after index BSI, in patients with documented clinical cure and completion of therapy for the initial episode. Results: Of the 856 analysed patients: 426 received short and 430 received long therapy. All-cause mortality at day 90 occurred in 47 patients; on multivariate analysis, short therapy was not associated with a higher risk of mortality, also after adjusting the model for the propensity score of receiving short therapy. Relapse occurred in 42 patients. Independent risk factors for relapse using death as competing risk were immunosuppression (subhazard ratio 4.67, p < 0.001), and end-stage liver disease (subhazard ratio 2.58, p 0.013). The propensity-weighted estimation of the average treatment effect for relapse reduction with long therapy (>10 days) was -1.6% (p 0.26) in the total population, and -7.1% (p 0.18) in immunocompromised patients. Conclusions: We could not identify shorter treatment duration as a risk factor for mortality and for relapse in patients with E. coli BSI. open Giannella, M.*; Pascale, R.; Toschi, A.; Ferraro, G.; Graziano, E.; Furii, F.; Bartoletti, M.; Tedeschi, S.; Ambretti, S.; Lewis, R.E.; Viale, P. Giannella, M.*; Pascale, R.; Toschi, A.; Ferraro, G.; Graziano, E.; Furii, F.; Bartoletti, M.; Tedeschi, S.; Ambretti, S.; Lewis, R.E.; Viale, P.

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

none 18 no We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients. Palandri, F; Latagliata, R.; Polverelli, N.; Tieghi, A.; Crugnola, M.; Martino, B.; Perricone, M.; Breccia, M.; Ottaviani, E.; Testoni, N.; Merli, F.; Aversa, F.; Alimena, G.; Cavo, M.; Martinelli, G.; Catani, L.; Baccarani, M.; Vianelli, N. Palandri, F; Latagliata, R.; Polverelli, N.; Tieghi, A.; Crugnola, M.; Martino, B.; Perricone, M.; Breccia, M.; Ottaviani, E.; Testoni, N.; Merli, F.; Aversa, F.; Alimena, G.; Cavo, M.; Martinelli, G.; Catani, L.; Baccarani, M.; Vianelli, N.

open 12 no Increased glucose metabolism and reprogramming toward aerobic glycolysis are a hallmark of cancer cells, meeting their metabolic needs for sustained cell proliferation. Metabolic reprogramming is usually considered as a downstream consequence of tumor development and oncogene activation; growing evidence indicates, however, that metabolism on its turn can support oncogenic signaling to foster tumor malignancy. Here, we explored how glucose metabolism regulates gene transcription and found an unexpected link with YAP/TAZ, key transcription factors regulating organ growth, tumor cell proliferation and aggressiveness. When cells actively incorporate glucose and route it through glycolysis, YAP/TAZ are fully active; when glucose metabolism is blocked, or glycolysis is reduced, YAP/TAZ transcriptional activity is decreased. Accordingly, glycolysis is required to sustain YAP/TAZ pro‐tumorigenic functions, and YAP/TAZ are required for the full deployment of glucose growth‐promoting activity. Mechanistically we found that phosphofructokinase (PFK1), the enzyme regulating the first committed step of glycolysis, binds the YAP/TAZ transcriptional cofactors TEADs and promotes their functional and biochemical cooperation with YAP/TAZ. Strikingly, this regulation is conserved in Drosophila, where phosphofructokinase is required for tissue overgrowth promoted by Yki, the fly homologue of YAP. Moreover, gene expression regulated by glucose metabolism in breast cancer cells is strongly associated in a large dataset of primary human mammary tumors with YAP/TAZ activation and with the progression toward more advanced and malignant stages. These findings suggest that aerobic glycolysis endows cancer cells with particular metabolic properties and at the same time sustains transcription factors with potent pro‐tumorigenic activities such as YAP/TAZ. open Enzo E; Santinon G; Pocaterra A; Aragona M; Bresolin S; Forcato M; Grifoni D; Pession A; Zanconato F; Guzzo G; Bicciato S; Dupont S Enzo E; Santinon G; Pocaterra A; Aragona M; Bresolin S; Forcato M; Grifoni D; Pession A; Zanconato F; Guzzo G; Bicciato S; Dupont S

none 18 si The implementation of new surgical techniques offers chances but carries risks. Usually, several years pass before a critical appraisal and a balanced opinion of a new treatment method are available and rely on the evidence from the literature and expert's opinion. The frozen elephant trunk (FET) technique has been increasingly used to treat complex pathologies of the aortic arch and the descending aorta, but there still is an ongoing discussion within the surgical community about the optimal indications. This paper represents a common effort of the Vascular Domain of EACTS together with several surgeons with particular expertise in aortic surgery, and summarizes the current knowledge and the state of the art about the FET technique. The majority of the information about the FET technique has been extracted from 97 focused publications already available in the PubMed database (cohort studies, case reports, reviews, small series, meta-analyses and best evidence topics) published in English. Shrestha, M.; Bachet, J.; Bavaria, J.; Carrel, T.P.; De Paulis, R.; Di Bartolomeo, R.; Etz, C.D.; Grabenwöger, M.; Grimm, M.; Haverich, A.; Jakob, H.; Martens, A.; Mestres, C.A.; Pacini, D.; Resch, T.; Schepens, M.; Urbanski, P.P.; Czerny, M. Shrestha, M.; Bachet, J.; Bavaria, J.; Carrel, T.P.; De Paulis, R.; Di Bartolomeo, R.; Etz, C.D.; Grabenwöger, M.; Grimm, M.; Haverich, A.; Jakob, H.; Martens, A.; Mestres, C.A.; Pacini, D.; Resch, T.; Schepens, M.; Urbanski, P.P.; Czerny, M.

none 8 no Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC) analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD. Abruzzo, Provvidenza M.; Ghezzo, Alessandro; Bolotta, Alessandra; Ferreri, Carla; Minguzzi, Renato; Vignini, Arianna; Visconti, Paola; Marini, Marina Abruzzo, Provvidenza M.; Ghezzo, Alessandro; Bolotta, Alessandra; Ferreri, Carla; Minguzzi, Renato; Vignini, Arianna; Visconti, Paola; Marini, Marina

none 6 no Hepatitis C negatively changes patient quality of life even in the absence of advanced liver disease. The specific patterns of quality of life of hepatitis C positive patients waiting for transplant or after surgery are not widely studied. Areas covered: A significant percentage of infected patients show cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by the liver disease. Depression can be diagnosed in one third of hepatitis C positive patients. Conflicting data are available regarding the possible role of Model for End-Stage Liver Disease score as predictor of impaired quality of life. In the first period after liver transplant, quality of life tends to increase at the pre-transplant period but in the medium and long-term period, it declines. The recurrence of hepatitis C infection represents a strong predictor of morbidity and mortality and can significantly affect the global quality of life of patients. Expert commentary: Hepatologists, surgeons and psychologists should collaborate to support infected patients in all phases of transplant including the long-term period after surgery. Education and information should be implemented especially regarding the positive role of new direct antivirals. none Golfieri, Lucia; Gitto, Stefano; Morelli, Maria Cristina; Pinna, Antonio Daniele; Grandi, Silvana; Andreone, Pietro Golfieri, Lucia; Gitto, Stefano; Morelli, Maria Cristina; Pinna, Antonio Daniele; Grandi, Silvana; Andreone, Pietro

none 8 no Objective/Background: Cataplexy is the pathognomonic symptom of narcolepsy type 1 (NT1). Since it is considered difficult to be directly observed or documented by clinicians, its diagnosis relies mainly on history taking. Our study aimed at testing the feasibility of a standardized video recording procedure under emotional stimulation to document cataplexy in the diagnostic work-up of suspected hypersomnia of central origin. Patients/Methods: Two-hundred-eight consecutive patients underwent the diagnostic work-up and reached the final diagnosis of NT1 (n = 133), idiopathic hypersomnia or narcolepsy type 2 (IH/NT2 group, n = 33), or subjective excessive daytime sleepiness (sEDS group, n = 42). All subjects underwent a standardized video recording procedure while watching funny movies selected according to individual preferences, and a technician blind to clinical features reviewed the recordings to identify hypotonic phenomena that were finally confirmed by patients. Results: The video recording under emotional stimulation captured hypotonic phenomena in 72.2%, 9.1% and 4.8% of NT1, IH/NT2, and sEDS subjects (p < 0.0001), respectively. When tested against CSF hypocretin deficiency, the documentation of a hypotonic episode at the test showed an area under the ROC curve of 0.823 ± 0.033 (p < 0.0001). NT1 patients under anticataplectic medications showed less frequently hypotonic episodes than untreated ones (48.0% vs 77.8%, p = 0.003). Conclusions: A standardized video recording procedure under emotional stimulation can help in the characterization of suspected hypersomnia of central origin. Further multi-center studies are warranted to extend the present findings and integrate a shared procedure for the laboratory work-up of narcolepsy. Vandi, Stefano; Pizza, Fabio; Antelmi, Elena; Neccia, Giulia; Iloti, Martina; Mazzoni, Alice; Avoni, Patrizia; Plazzi, Giuseppe Vandi, Stefano; Pizza, Fabio; Antelmi, Elena; Neccia, Giulia; Iloti, Martina; Mazzoni, Alice; Avoni, Patrizia; Plazzi, Giuseppe