Search

SummaryAtrial fibrillation (AF) patients are at high risk for thrombotic and vascular events related to their cardiac arrhythmia and underlying systemic atherosclerosis. Ankle-Brachial Index (ABI) is a non-invasive tool in evaluating systemic atherosclerosis, useful in predicting cardiovascular events in general population; no data are available in AF patients. ARAPACIS is a prospective multicentre observational study performed by the Italian Society of Internal Medicine, analysing association between low ABI (≤0.90) and vascular events in NVAF out- or in-patients, enrolled in 136 Italian centres. A total of 2,027 non-valvular AF (NVAF) patients aged > 18 years from both sexes followed for a median time of 34.7 (interquartile range: 22.0–36.0) months, yielding a total of 4,614 patient-years of observation. Mean age was 73 ± 10 years old with 55% male patients. A total of 176 patients (8.7%) experienced a vascular event, with a cumulative incidence of 3.81%/patient-year. ABI≤ 0.90 was more prevalent in patients with a vascular event compared with patients free of vascular events (32.2 vs 20.2%, p< 0.05). On Cox proportional hazard analysis, ABI≤ 0.90 was an independent predictor of vascular events (hazard ratio (HR): 1.394, 95% confidence interval (CI): 1.042–1.866; p=0.02), vascular death (HR: 2.047, 95% CI: 1.255-3.338; p=0.004) and MI (HR: 2.709, 95%> CI: 1.485-5.083; p=0.001). This latter association was also confirmed after excluding patients with previous MI (HR: 2.901, 95% CI: 1.408-5.990, p=0.004). No association was observed between low ABI and stroke/transient ischaemic attack (p=0.91). In conclusion, low ABI is useful to predict MI and vascular death in NVAF patients and may independently facilitate cardiovascular risk assessment in NVAF patients.Note: The review process for this paper was fully handled by C. Weber, Editor in Chief.Listed in the Supplementary Online Appendix Material which is available online at www.thrombosis-online.com.

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. To address this issue, the Italian Society of Internal Medicine (SIMI) established an Italian registry documenting ABI in NVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI ≤0.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy 0.90 (93% vs. 82%; p < 0.0001). Logistic regression analysis demonstrated that ABI ≤0.90 was significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age class ≥75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p = 0.002). Vascular disease, as assessed by the history elements of CHA2DS2VASc score, was recorded in 17.3% of patients; inclusion of ABI ≤0.90 in the definition of vascular disease yielded a total prevalence of 33%. A higher prevalence of vascular disease was detected if ABI ≤0.90 was included in the CHA2DS2VASc score (Fig. 1). CHA2DS2VASc including ABI ≤0.90 was more associated with previous stroke (43%; OR: 1.85; 95% CI: 1.41 to 2.44; p < 0.0001) compared to CHA2DS2VASc with ABI 0.91 to 1.39 (23%; OR: 1.52; 95% CI: 1.10 to 2.11; p = 0.0117). To the best of our knowledge, there is no large-scale study that specifically examined the prevalence of ABI ≤0.90 in NVAF. In our population, 21% had ABI ≤0.90 indicating that NVAF is often associated with systemic atherosclerosis. The CHADS2 has been recently refined with the CHA2DS2-VASc score, which includes vascular disease as documented by a history of AMI, symptomatic PAD, or detection of atherosclerotic plaque in the aortic arch (4). Comparison of vascular prevalence as assessed by CHA2DS2-VASc score and/or ABI ≤0.90 is of interest to define the potentially positive impact of measuring ABI in the management of NVAF patients. Inclusion of ABI ≤0.90 in the definition of vascular disease greatly increased the prevalence of vascular disease, which increased from 17.3% (based on history alone) to 33% (based on ABI) in the entire population. If ABI ≤0.90 was encompassed in the definition of vascular disease of CHA2DS2-VASc score the prevalence of vascular disease increased in every risk class. Inclusion of ABI ≤0.90 in the CHA2DS2-VASc score allowed us to better define the risk profile of NVAF patients with an up-grading of the risk score in each CHA2DS2-VASc score category. This may have important therapeutic implications if the new score could be tested prospectively, as a higher number of NVAF patients would potentially be candidates for an anticoagulant treatment by measuring ABI. A prospective study is, therefore, necessary to validate the risk score of this new definition of vascular disease. In conclusion, this study provides the first evidence that one-fifth of NVAF patients had an ABI ≤0.90, indicating that it may represent a simple and cheap method to better define the prevalence of vascular disease in NVAF.

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.

none 4 si Background: Benzodiazepines and other hypnotic alternatives are associated with increased risks of adverse events. Heightened awareness of risks may have changed prescribing habits over the years. However, these trends are not fully described, especially in vulnerable people such as multimorbid older adults. Objective: We aimed to describe the annual prevalence of benzodiazepine and other hypnotic use in relation to multimorbidity among older adults in the province of Quebec, Canada, from 2000 to 2016. Method: We conducted a population-based study using the Quebec Integrated Chronic Disease Surveillance System. We included all individuals aged ≥66 years covered by the public drug plan. For each year, we evaluated the sex- and age-standardized proportion of benzodiazepine and other hypnotic users, defined as individuals with at least one drug claim in the year. We stratified our results according to multimorbidity and used log-binomial regression to study trends. Results: The proportion of individuals using benzodiazepines decreased from 34.8% in 2000 to 24.8% in 2016 (p for trend

open 3 no This research was funded by CARISBO Foundation, grants numbers 2021.0058 to C.G and 2021.0173 to S.N.; Italian Minister of University and Research—Rita Levi Montalcini Program-Rientro cervelli RLM2017 to C.G. The ATP synthase is a mitochondrial inner membrane complex whose function is essential for cell bioenergy, being responsible for the conversion of ADP into ATP and playing a role in mitochondrial cristae morphology organization. The enzyme is composed of 18 protein subunits, 16 nuclear DNA (nDNA) encoded and two mitochondrial DNA (mtDNA) encoded, organized in two domains, FO and F1. Pathogenetic variants in genes encoding structural subunits or assembly factors are responsible for fatal human diseases. Emerging evidence also underlines the role of ATP-synthase in neurodegenerative diseases as Parkinson’s, Alzheimer’s, and motor neuron diseases such as Amyotrophic Lateral Sclerosis. Post-translational modification, epigenetic modulation of ATP gene expression and protein level, and the mechanism of mitochondrial transition pore have been deemed responsible for neuronal cell death in vivo and in vitro models for neurodegenerative diseases. In this review, we will explore ATP synthase assembly and function in physiological and pathological conditions by referring to the recent cryo-EM studies and by exploring human disease models. open Garone C.; Pietra A.; Nesci S. Garone C.; Pietra A.; Nesci S.

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

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.

Study Objectives Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID‐19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. Methods In the period between 10 April and 15 May 2020, we performed routine follow‐up visits by telephone (as recommended during the COVID‐19 emergency) to 50 patients >18 years old (40% males) under stable long‐term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job (“lost occupation”). Current sleep–wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. Results At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep‐related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. Conclusions Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight., The graphical abstract displays that NT1 patients working/studying at home slept more with improved subjective daytime sleepiness, while both NT1 patients working/studying at home and loosing occupation because of the pandemic significantly increased BMI.

open 3 no The use of albumin in patients with cirrhosis has been extensively discussed over recent years. Current treatment approaches depend on targeting related complications, aiming to treat and/or prevent circulatory dysfunction, bacterial infections and multi-organ failure. Albumin has been shown to prolong survival and reduce complications in patients with cirrhosis. This review aims to ascertain whether the use of albumin is justified in patients with cirrhosis. A systematic review of randomized controlled trials (RCTs) and meta-analyses evaluating albumin use in patients with cirrhosis published between 1985 and February 2020 was conducted; the quality and risk of bias of the included studies were assessed. In total, 45 RCTs and 10 meta-analyses were included. Based on the included evidence, albumin is superior at preventing and controlling the incidence of cirrhosis complications vs other plasma expanders. Recent studies reported that long-term albumin administration to patients with decompensated cirrhosis improves survival with a 38% reduction in the mortality hazard ratio compared with standard medical treatment alone. Albumin infusions are justified for routine use in patients with cirrhosis, and the use of albumin either alone or in combination with other treatments leads to clinical benefits. Long-term administration of albumin should be considered in some patients. Medical writing assistance was provided by Meridian HealthComms Ltd in accordance with good publication practice (GPP3), funded by CSL Behring. open Giacomo Zaccherini; Manuel Tufoni; Mauro Bernardi Giacomo Zaccherini; Manuel Tufoni; Mauro Bernardi

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.

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.

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

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 5 no Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed. mixed Tovoli, Francesco; Renzulli, Matteo; Granito, Alessandro; Golfieri, Rita; Bolondi, Luigi Tovoli, Francesco; Renzulli, Matteo; Granito, Alessandro; Golfieri, Rita; Bolondi, Luigi

none 24 si Published Online December 5, 2016 Background: There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. Methods: In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with . ClinicalTrials.gov, number . NCT01774344. Findings: Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p

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.

reserved 19 no Objectives: The Yaghnobis are an ethno-linguistic minority historically settled along the Yaghnob River in the Upper-Zarafshan Valley in Tajikistan. They speak a language of Old Sogdian origin, which is the only present-day witness of the Lingua Franca used along the Silk Road in Late Antiquity. The aim of this study was to reconstruct the genetic history of this community in order to shed light on its isolation and genetic ancestry within the Euro-Asiatic context. Materials and Methods: A total of 100 DNA samples were collected in the Yaghnob and Matcha Valleys during several expeditions and their mitochondrial, Y-chromosome and autosomal genome-wide variation were compared with that from a large set of modern and ancient Euro-Asiatic samples. Results: Findings from uniparental markers highlighted the long-term isolation of the Yaghnobis. Mitochondrial DNA ancestry traced an ancient link with Middle Eastern populations, whereas Y-chromosome legacy showed more tight relationships with Central Asians. Admixture, outgroup-f3, and D-statistics computed on autosomal variation corroborated Y-chromosome evidence, pointing respectively to low Anatolian Neolithic and high Steppe ancestry proportions in Yaghnobis, and to their closer affinity with Tajiks than to Iranians. Discussion: Although the Yaghnobis do not show evident signs of recent admixture, they could be considered a modern proxy for the source of gene flow for many Central Asian and Middle Eastern groups. Accordingly, they seem to retain a peculiar genomic ancestry probably ascribable to an ancient gene pool originally wide spread across a vast area and subsequently reshuffled by distinct demographic events occurred in Middle East and Central Asia. mixed Cilli, Elisabetta*; Sarno, Stefania; Gnecchi Ruscone, Guido Alberto; Serventi, Patrizia; De Fanti, Sara; Delaini, Paolo; Ognibene, Paolo; Basello, Gian Pietro; Ravegnini, Gloria; Angelini, Sabrina; Ferri, Gianmarco; Gentilini, Davide; Di Blasio, Anna Maria; Pelotti, Susi; Pettener, Davide; Sazzini, Marco; Panaino, Antonio; Luiselli, Donata; Gruppioni, Giorgio Cilli, Elisabetta*; Sarno, Stefania; Gnecchi Ruscone, Guido Alberto; Serventi, Patrizia; De Fanti, Sara; Delaini, Paolo; Ognibene, Paolo; Basello, Gian Pietro; Ravegnini, Gloria; Angelini, Sabrina; Ferri, Gianmarco; Gentilini, Davide; Di Blasio, Anna Maria; Pelotti, Susi; Pettener, Davide; Sazzini, Marco; Panaino, Antonio; Luiselli, Donata; Gruppioni, Giorgio

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

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 8 BACKGROUND: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. RESULTS: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). CONCLUSIONS: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn. Petrillo, M; De Iaco, P; Cianci, S; Perrone, M; Costantini, B; Ronsini, C; Scambia, G; Fagotti, A3. Petrillo, M; De Iaco, P; Cianci, S; Perrone, M; Costantini, B; Ronsini, C; Scambia, G; Fagotti, A3.

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

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

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*

none 6 no Published online: 09 October 2017 Background:: Evidence concerning when and in which manner older people living in nursing homes (NHs) would prefer to discuss advance care planning (ACP) is still scarce. This study explored the attitudes of NH residents and family members toward ACP and their opinions as to the right time to broach the subject, the manner in which it should be approached, and the content of ACP. Methods:: This was a qualitative study using face-to-face interviews with 30 residents (age range 66–94), and 10 family members from 4 Italian NHs. The interviews were analyzed using content analysis. Results:: Three main themes were identified: (1) life in the NH, including thoughts about life in a nursing home, residents’ concerns, wishes and fears, and communication barriers; (2) future plans and attitudes toward ACP, including attitudes toward planning for the future and plans already made, and attitudes toward and barriers against ACP; (3) contents and manner of ACP, including contents of ACP discussions, the right moment to introduce ACP, with whom it is better to discuss ACP, and attitudes toward advance directives. Conclusions:: ACP was a welcome intervention for the majority of participants, but an individualized assessment of the person's readiness to be involved in ACP is needed. For people with dementia, it is essential to identify the right time to introduce ACP before NH admission. Participants in our study suggested that ACP should include palliative care and practical issues, and that in the NH setting all staff and family members may have a valuable role in ACP. none Ingravallo, Francesca; Mignani, Veronica; Mariani, Elena; Ottoboni, Giovanni; Melon, Marie Christine; Chattat, Rabih Ingravallo, Francesca; Mignani, Veronica; Mariani, Elena; Ottoboni, Giovanni; Melon, Marie Christine; Chattat, Rabih

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 107 si Non presente mixed Valgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, Tim Valgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, Tim

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.

This editorial refers to ‘Natural history of patients with insignificant coronary artery disease’, by R. Tavella et al ., on page 117. Chest pain is the most common symptom of coronary artery disease (CAD) prompting subjects to seek attention from physicians. Angina is an important predictor of outcomes and to a large extent determines health-related quality of life (HRQoL) even in the overall apparently health population.1 Furthermore, physical disability caused by angina has an impact on prognosis as well as on HRQoL.2 Early reports have demonstrated the value of supplementing the clinical presentation of angina with angiographic information.3 Angiography does not miss significant life-threatening disease. The severity and the extent of obstructive coronary lesions demonstrated by angiography are powerful predictors of death. Clinical presentation is also a strong predictor of mortality, as type and severity of chest pain act indirectly as predictors because of their association with the severity of the coronary stenosis. For this reason, studies designed to evaluate the influence of medical or interventional therapy on survival and/or HRQoL should utilize angiographic findings in the selection of groups of patients. The results of the study by Tavella et al .4 are at variance with these ‘rules of thumb’. These authors looked at patients with stable CAD and reported 1% of recurrence of myocardial infarction in a group of 253 patients with chest pain and non-obstructive CAD who were followed for 12 months. Similar outcomes were found in those patients labelled as obstructive CAD who, indeed, had clinically negligible differences in prognosis: 1% death and 1% myocardial infarction during the same time span. Similarity was even more when evaluating HRQoL status in the two groups of patients. These findings raise several important issues. The population reported by Tavella et al .4 was highly selected in … [↵][1]*Corresponding author. Tel: +39 051 347290, Fax: +39 051 347290, Email: raffaele.bugiardini{at}unibo.it [1]: #xref-corresp-1-1

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 4 no Objective: We aimed to search and synthesize qualitative studies exploring the perspectives of older people living in long-term care facilities and of their family members about advance care planning (ACP) discussions. Methods: The enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) framework was used to guide the review and report its results. PubMed, CINAHL, and PsycINFO were searched for studies published between January 2000 and November 2015. All included studies were assessed for comprehensiveness of reporting, and a thematic synthesis of their results was performed. Results: The nine included studies differed in terms of qualitative method used, comprehensiveness of reporting, and geographical origin. The thematic synthesis led to the identification of four main themes: 1) plans already made; 2) end-of-life care and decision-making; 3) opinions and attitudes toward ACP; and 4) how, when, about what, and with whom to do ACP. Conclusion: Despite their willingness to be involved in a shared decision-making process, older residents and their families still have little experience with ACP. Practical implications: In view of implementing ACP for elders living in long-term care facilities, it would be important to rethink ACP and also to incorporate their nonmedical preferences, according to their own priorities. Mignani, Veronica; Ingravallo, Francesca; Mariani, Elena; Chattat, Rabih Mignani, Veronica; Ingravallo, Francesca; Mariani, Elena; Chattat, Rabih

none 11 si It is a matter of fact that the human gut microbiome also includes a non-bacterial fraction represented by eukaryotic cells and viruses. To further explore the gut microbiome variation in human populations, here we characterized the human DNA viral community from publicly available gut metagenome data sets from human populations with different geographical origin and lifestyle. In particular, such data sets encompass microbiome information from two western urban societies (USA and Italy), as well as two traditional hunter-gatherer communities (the Hadza from Tanzania and Matses from Peru) and one pre-agricultural tribe (Tunapuco from Peru). Our results allowed for the first taxonomic reconstruction of the complex viral metacommunities within the human gut. The core virome structure included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses and anelloviruses. Using Random Forests and a co-occurrence analysis approach, we identified the viruses that distinguished populations according to their geographical origin and/or lifestyle. This paves the way for new research aimed at investigating the biological role of the gut virome in human physiology, and the importance of our viral counterpart in the microbiome-host co-evolutionary process. none Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L; Soverini, Matteo; Quercia, Sara; Barone, Monica; Castagnetti, Andrea; Biagi, Elena; Gallinella, Giorgio; Brigidi, Patrizia; Candela, Marco Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L; Soverini, Matteo; Quercia, Sara; Barone, Monica; Castagnetti, Andrea; Biagi, Elena; Gallinella, Giorgio; Brigidi, Patrizia; Candela, Marco

none 20 no The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged

none 28 no Objective: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of “low grade epilepsy associated neuroepithelial tumors” (LEATs). Methods: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. Results: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (pÂ

none 15 si Introduction: Previous works have shown that women hospitalized with STEMI have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary PCI. Purpose: We sought to investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications and primary PCI in this excess of risk. Methods: From January 2010 to January 2016, a total of 8834 patients have been hospitalized and received medical treatment for STEMI in 41 hospitals, referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776). Logistic regression model was adjusted to covariates significantly different between groups in univariate analysis. The endpoint was 30-day mortality after STEMI. Results: There were 2657 women and 6177 men. Women were older than man, with a higher prevalence of risk factors and comorbidities. Fewer women than men presented within 2 hours from symptom onset (p

none 6 no In the Survival of Myocardial Infarction Long-term Evaluation (SMILE) 1, 3, and 4 studies, early administration of zofenopril in acute myocardial infarction showed to be prognostically beneficial versus placebo or ramipril. The SMILE-2 showed that both zofenopril and lisinopril are safe and showed no significant differences in the incidence of major cardiovascular (CV) complications. In this pooled analysis of individual data of the SMILE studies, we evaluated whether the superior efficacy of zofenopril is maintained also in patients with 1 CV risk factor (CV+, n = 2962) as compared to CV2 (n = 668). The primary study end point was set to 1-year combined occurrence of death or hospitalization for CV causes. The risk of CV events was significantly reduced with zofenopril versus placebo either in the CV+ (237%; hazard ratio: 0.63; 95% confidence interval: 0.51-0.78; P = 0.0001) or in the CV2 group (255%; hazard ratio: 0.45; 0.26-0.78; P = 0.004). Also, the other angiotensinconverting enzyme inhibitors reduced the risk of major CV outcomes, though the reduction was not statistically significant versus placebo (CV+: 0.78; 0.58-1.05; P = 0.107; CV2: 0.71; 0.36-1.41; P = 0.334). The benefit was larger in patients treated with zofenopril than other angiotensin-converting enzyme inhibitors, with a statistically significant difference for CV+ (0.79; 0.63-0.99; P = 0.039) versus CV2 (0.62; 0.37-1.06; P = 0.081). In conclusion, zofenopril administered to patients after acute myocardial infarction has a positive impact on prognosis, regardless of the patient's CV risk profile. none Borghi, Claudio; Omboni, Stefano; Reggiardo, Giorgio; Bacchelli, Stefano; Esposti, Daniela Degli; Ambrosioni, Ettore Borghi, Claudio; Omboni, Stefano; Reggiardo, Giorgio; Bacchelli, Stefano; Esposti, Daniela Degli; Ambrosioni, Ettore

none 10 no I n 1996, Lucio Gullo coined the term “benign pancreatic hyperenzymemia” (BPH) for a condition characterized by a chronic increase of serum amylase, pancreatic isoamylase, lipase, and trypsin detectable in healthy people without any clinically or imaging-proven evidence of organic disease.1 Increased pancreatic enzymes levels are usually detected accidentally mainly as a result of screening tests in otherwise asymptomatic subjects. The exact incidence of the condition is unknown. The knowledge so far acquired on the BPH allowed for the identification of the following major laboratory and clinical features: (a) most often, the enzyme elevation is 2 to 4 times the normal range, but it can sometimes be much higher, increasing up to 15 times; (b) it occurs in adult and pediatric asymptomatic subjects, lacking any pancreatic or systemic diseases; (c) it persists over time with considerable fluctuations in serum enzyme concentration, including periods with normal values; (d) it can be either familial, when at least 1 family member shows the same abnormality, or sporadic; and (e) after the initial finding, the hyperenzymemia should be considered benign only after at least 2 years of follow-up, during which all imaging tests, that is, pancreatic computed tomography (CT) scans and/or magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRCP), must be negative. Despite this progress, the finding of increased pancreatic enzymes raises the suspicion of an underlying pancreatic disease in most physicians. As a result, asymptomatic subjects undergo numerous, expensive, and often useless investigations increasing health care costs and patients' concerns.2 Thus, the aim of this brief review is to provide the general practitioners and gastroenterologists with an update on the clinical and diagnostic features of BPH to guarantee a proper management of these otherwise healthy subject Birtolo, Chiara; Migliori, Marina; Drewes, Asbjørn M.; Tomassetti, Paola; Imbrogno, Andrea; Fusaroli, Pietro; Casadei, Riccardo; Ricci, Claudio; Stanghellini, Vincenzo; De Giorgio, Roberto Birtolo, Chiara; Migliori, Marina; Drewes, Asbjørn M.; Tomassetti, Paola; Imbrogno, Andrea; Fusaroli, Pietro; Casadei, Riccardo; Ricci, Claudio; Stanghellini, Vincenzo; De Giorgio, Roberto

none 5 no Introduction: Keratocyst is a cystic lesion that has distinctive histological features composed of an epithelial lining with surface keratinization that is corrugated and predominantly parakeratotic. Although rare, they present in human pathology mainly as odontogenic keratocysts and have occasional association with Gorlin-Goltz syndrome. Case report: We present a neonate with an antenatal suspicion of congenital pulmonary airway mal- formation. While stable and imaging confirmation studies were accomplished, thoracoscopic exploration and excision of a bronchogenic-like lung cyst attached to an extralobar pulmonary sequestration supero- medial to the left upper lobe were performed successfully at day 44 of life. Histopathological study has revealed keratocystic features of the lung cyst attached to a pulmonary sequestration tissue. Discussion and conclusion: Up to our knowledge and review of the literature, this is the first case and occurrence of Lung Keratocyst. Long-term follow up is needed to assess the outcome of the thoracoscopic management of such lesion, and its hypothetic relation with odontogenic keratocysts or any associated syndromes. open Lima, Mario; Gargano, Tommaso; Al-Taher, Raed; Maffi, Michela; Salfi, Nunzio Lima, Mario; Gargano, Tommaso; Al-Taher, Raed; Maffi, Michela; Salfi, Nunzio

none 3 no ISSN 1125-9390 open access su infezmed.it In the late nineteenth century, with industrial growth and the resulting mass urbanisation, tuberculosis represented a plague mainly among the poor social classes. The outdated and crowded Italian prisons (formerly old monasteries) during the early 1900s were insufficient to "host" the multitude of inmates condemned or waiting for judgment. Italian prisoners were beset by hunger and poor hygiene facilities. Clothes did not differ between winter and summer. The Criminal Sanatorium of Pianosa was officially inaugurated in 1907, but from the 1860s it had been set up to host an agricultural penal colony. Here we report the excellent results obtained between 1907 and 1909 in the management of tuberculosis among prisoners in Pianosa, where surgery was also available. In those times, climate therapy with an enriched and varied nutrition was the only effective treatment for tuberculosis. Overall, of the 913 prisoners housed in Pianosa in that period and according to the acknowledged scientific criteria, the following results were achieved: complete cure in 182, improvement in 416, mild amelioration in 94, worsening in 80, no change in 20. The number of prisoners who died or were transferred to another prison is unknown. The case series of the prison hospital in Pianosa may be reconstructed thanks to data published by the Director Roberto Passini. The better outcome of the prisoners in Pianosa, in comparison with inmates of other Italian institutions, was due both to treatment standards (climate, nutritional, hygienic, and surgical) and to the proportionally longer period of stay in Pianosa for prisoners with already confirmed detention periods Sergio, Sabbatani; Sirio, Fiorino; Roberto, Manfredi Sergio, Sabbatani; Sirio, Fiorino; Roberto, Manfredi