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Glypican-3 (GPC-3) is a heparan sulfate proteoglycan overexpressed by hepatocellular carcinoma (HCC) cells. Several studies highlighted the diagnostic and prognostic value of GPC-3 expression in liver tissue, while data on the reliability of serum GPC-3 are limited and conflicting. We aimed to evaluate the prognostic value of serum GPC-3 in patients with HCC.A total of 449 patients (91 F and 358 M; median age 65 [38-86] years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were retrospectively analyzed. All patients had cirrhosis and the main underlying etiology was viral (N.=323, 72%). Barcelona Clinic Liver Cancer (BCLC) staging system was adopted for patients' classification (BCLC 0/A, N.=293, 65% vs. B/C/D, N.=156, 35%) and treatment allocation. Response to therapy was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST).Median overall survival (OS) after HCC diagnosis was 30 months (95% confidence interval [CI]: 27-34). Patients with serum GPC-3150 pg/mL showed lower overall survival (16; 95%CI: 13-24 months) compared to those with GPC-3≤150 pg/mL (36; 95%CI: 30-56 months) (Log-rank test, P0.001). At multivariate Cox proportional-hazard regression analysis, presence of ascites (adjusted Hazard Ratio [aHR]=1.84; 95%CI: 1.23-2.74, P=0.003), BCLC stage (aHR=1.65; 95%CI: 1.39-1.97, P0.001), mRECIST (aHR=0.33; 95%CI: 0.21-0.51, P0.001) and GPC-3150 pg/mL (aHR=2.02; 95%CI: 1.47-2.78, P0.001) resulted significantly associated to overall survival.Serum GPC-3 resulted an independent prognostic factor for patients with HCC irrespectively from tumor stage and response to therapy.

Background Volatiles organic metabolites (VOMs) are a large group of carbon-bound chemicals elements, gaseous at room temperature that are the products of metabolism. There is increasing evidence that variations in faecal VOMs indicate gastroenterological diseases. No study assessed VOMs in the setting of predicting therapeutic response in inflammatory bowel disease (IBD). Methods We conducted a prospective study in which we consecutively recruited IBD patients with indications for treatment with biologics. The primary outcome of our study was the evaluation of prediction ability of VOMs of clinical response at 12 months of adalimumab or vedolizumab therapy. Secondary outcomes included correlations of VOM with clinical features of IBD. Results We recruited 50 patients with IBD whose stools were analysed with gold standard technique mass spectrometer (MS) / gas chromatography (GC). Thirty-one patients were treated with adalimumab (of which 30 Crohn’s disease, and 1 ulcerative colitis, UC), 19 patients with vedolizumab (of which 12 CD and 7 UC). VOMs were not influenced by age, disease duration, sex, smoking habit. Two VOMs, octenol and, in particular, methyl indole were able to distinguish ulcerative colitis (UC) from Crohn’s disease (CD) (AUC = 0.72 and 0.85, respectively) and correlate with higher inflammation markers (C-reactive protein, CRP and calprotectin, respectively). Methylbutanal, instead, was a marker of CD and, in particular, of ileal location (p = 0.01). These results were confirmed at principal component analysis (PCA). Lower levels of ethanol and methyl butanoate correlated with disease remission. Methyl butanoate was able to distinguish remission from active clinical disease, with an accuracy at least equal to that of calprotectin (AUC = 0.69 and AUC = 0.62, respectively). We furthermore demonstrated pre-biologics methyl butyrate prediction ability of clinical response after 12 months of therapy (AUC = 0.68, 95%CI = 0.53-0.81, p = 0.02). Lower levels of methyl indole or of octenol or higher levels of indole were able to predict calprotectin Conclusion The characterization of the intestinal metabolome, using VOMs technology, seems to be a promising method for better characterizing IBD and better speculating on their etiopathogenesis.

In recent years, there has been growing interest in the comprehension of the physiology of intestinal permeability and microbiota; and how these elements could influence the pathogenesis of diseases. The term intestinal permeability describes all the processes that allow the passage of molecules as water, electrolytes and nutrients through the intestinal barrier by the paracellular or the transcellular transport systems with several implications for self-tolerance and not-self immunity. An increased permeability might induce a more significant interaction of the immune system with unknown external antigens. This might favor the onset of several immune-related extra-intestinal diseases including coeliac disease, diabetes mellitus type 1, bronchial asthma and inflammatory bowel diseases. Furthermore, the intestinal permeability interacts every day with microbiota, the complex system of mutualistic inhabitants and commensal microorganisms living in the healthy gut. Microbiota is implicated in physiological functions by actively participating in digestion, absorption, synthesis of vitamins and protection from external aggressions. The critical site where these processes occur is the small intestine to which this updated review is dedicated. Understanding its anatomy, its barrier structure and permeability modulation and its microbiota composition is the essential skill to comprehend the complex pathogenesis of several - not only gastroenterological - diseases.

Renal dysfunction often complicates the course of liver disease, resulting in higher morbidity and mortality. The accurate assessment of kidney function in these patients is essential to early identify, stage and treat renal impairment as well as to better predict the prognosis, prioritize the patients for liver transplantation and decide whether to opt for simultaneous liver-kidney transplants. This review analyses the available tools for direct or indirect assessment of glomerular filtration rate, focusing on the flaws and strengths of each method in the specific setting of cirrhosis. The aim is to deliver a clear-cut view on this complex issue, trying to point out which strategies to prefer in this context, especially in the peculiar setting of liver transplantation. Moreover, a glance is given at future promising tools for glomerular filtration rate assessment, including new biomarkers and new equations specifically modelled for the cirrhotic population.

Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.

Diarrhea represents a common manifestation of several gastrointestinal diseases. Infectious agents are the most common causes of diarrhea in developing countries, where the inadequate sanitation and hygiene are prevalent. In these countries, the scarcity of preventive measures as well as the limited health resources cause a substantial increase in incidence, morbidity and mortality due to infectious diseases, including diarrhea. Currently, with the availability of rapid and inexpensive air transportation millions of people travel for tourism, work and immigration from developing countries to industrialized countries and vice versa. This leads to a high number of imported pathogens such as parasites causing infectious diarrhea. Importantly, while most cases of parasitic diarrhea are short, mild and self-limited, other cases may be associated with chronic diarrhea and serious morbidity and mortality. The aim of the current review is to provide an update, from a clinician's point of view, of the main parasites causing diarrhea, with a focus on their diagnosis and management in the clinical setting.

The objective of this study was to determine the correlation between functional and radiological longitudinal change in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), and to test the OMERACT definition of clinically meaningful progression of pulmonary function tests (PFTs) for the prediction of ILD radiological evolution. We retrospectively retrieved high-resolution computed tomography (HRCT) studies and PFTs including DLco, both available at two time-points and performed within 6 months of each other, in SSc patients. A subset of patients was selected using a 12-24-month clinically oriented interval (n = 58). The extent of ILD at HRCT was scored according to a visual semi-quantitative method (SQCT). The correlation of absolute change (Δ) in the SQCT score with change in FVC and DLco was examined using Pearson's correlation coefficient. The concordance between the OMERACT criteria (≥ 10% FVC relative decline; or 5-10% FVC and ≥ 15% DLco relative decline) and SQCT categorical change (5% and 10%) was investigated. A total of 129 patients were enrolled. During 12-24-month follow-up, ΔSQCT was negatively correlated with ΔFVC (r = - 0.487, p = 0.0001) and ΔDLco (r = - 0.298, p = 0.023). Ten patients demonstrated CT progression ΔSQCT > 5%, among whom 5 with ΔSQCT > 10%. OMERACT criteria identified 25 patients with progressive SSc-ILD, of whom only 5 presented ΔSQCT > 5 and 3 presented ΔSQCT > 10%. In conclusion, change in radiological extent of SSc-ILD was correlated to functional decline in a limited time-frame. Repeated HRCT after 12-24 months may be useful for the longitudinal characterization of ILD evolution in patients with stable pulmonary function. Conversely, functional changes are suggestive of a concurrent radiological progression only after this interval. Key Points • In SSc patients, chest HRCT performed every 12-24 months can detect minimal but significant changes in ILD extent, even in subjects with stable pulmonary function. • PFT changes in 12-24 months are related to the radiological ILD progression. • OMERACT criteria might overlook patients with radiological progression. • Repeated chest HRCT may be useful for monitoring SSc-ILD when performed within 12 to 24 months from baseline in order to promptly detect progression and possibly impact on prognosis.

Background: B-cells have been suggested to play a role in the pathogenesis of systemic sclerosis (SSc), representing, therefore, a potential therapeutic target. Objectives: We aimed at investigating the 36-month outcomes of 20 SSc patients who underwent an intensified B-depletion therapy (IBCDT) scheme, including both Rituximab (RTX) and cyclophosphamide (CYC). Methods: Data from 20 severe patients (18 females and 2 males, mean age 66.7&plusmn, 11.0 years) with diffuse SSc (anti-topoisomerase I antibody in 95%) patients with multiorgan involvement including interstitial lung disease (ILD) treated with an IBCDT were prospectively collected. IBCDT comprehended: RTX 375&thinsp, mg/m2 administered for four weekly doses (on days 1, 8, 15, and 22), followed by two additional doses after 30 and 60 days, in addition to two administrations of 10&thinsp, mg/kg of intravenous CYC plus three methylprednisolone pulses (15&thinsp, mg/kg) and subsequently followed by oral prednisone rapidly tapered to low minimum dosage of 5 mg daily. In addition, 10patients with more severe functional respiratory impairment at baseline were also treated with RTX 500 mg every 4 months during the first year and two times a year during the second and the third year. Results: After 36 months of follow-up, we recorded significant amelioration in N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels (mean 385.4&plusmn, 517pg/mL at baseline to 279&plusmn, 543 after 36 months). In addition, a significant radiological improvement of ILD in 20% of patients (4/20) and a radiological stabilization with no sign of progression of interstitial involvement in 13/20 (65%) were documented. A total of 3 out of 20 (15%) patients experienced a worsening of the ILD. No patient showed further decrease in functional respiratory parameters, including forced vital capacity, forced expiratory volume in one second, and mean values of diffusing capacity for carbon monoxide Moreover, no patient showed any change in the ejection fraction and pulmonary artery pressure when comparing values at baseline and after 24 and 36 months of observation. No severe infection, renal flare, RTX-related side effects were observed. No patient died. Conclusions: Our findings support that the IBCDT was well tolerated and might be a promising therapeutic option for the management of SSc, especially in those subjects with multiorgan involvement that includes ILD.

The seismic events that occurred in central Italy in 2016 severely damaged the rich cultural heritage system present in the area hit by the earthquake. Particularly significant is the situation of the Marche Region, here it is necessary to intervene quickly and effectively in order to preserve and secure the damaged historical architectural heritage. Following the agreement signed in 2019 between the administration of the Municipality of San Ginesio and the Marche Polytechnic University, a collaboration has been established, which is the basis of the present research work, aimed at studying and deepening the possible actions to be undertaken to be able to repair, preserve and enhance the medieval walls of the city. The city walls, dating from the fourteenth century A.D., almost completely surround the historic center of the city and are characterized by the presence of a large part of the ancient fortifications such as towers, access doors, defensive walkways, loopholes, etc. Since there is no complete survey of the planimetric configuration and of the elevations of the medieval walls, updated to the situation created after the earthquake, the first phase of the research focused on data acquisition. Combining DJI Spark MMA1 photogrammetric UAV images with cloud point by Mobile laser SLAM Kaarta Stencil, the 3D-dimensional modelling of the walls was obtained with the accuracy related to the output scale of 1:200 and with a detail and complexity useful for the following conservative analysis. Once the data was acquired and processed, it was possible to carry out a complete analysis of the walls structure, identifying the materials and construction techniques, the state of preservation of the materials, the damage situation to the structures, the various construction phases with the consequent relative dating. The analytical phase was concluded, therefore, with the identification and cataloging of the types of walls present. Each of these has been characterized both from a typological and a technical construction point of view, defining the wall quality (IQM) and the consequent mechanical parameters through the calculation process of the Wall Quality Index.

Infection is a significant complication in oncological megaprostheses. The purpose of our study is to indagate the innovations and new trend about the prevention of infection in this kind of surgery. The research focused on the use of antimicrobic prophylaxis, the defensive antibacterial coating and the use of silver coated.

Ceramic materials are widely used in hip prosthetic surgery. Faced with important developments in the design and characteristics of the materials, ceramic-on-ceramic (CoC) are today the bearings in Total Hip Replacement (THR) showing the minimal wear rate. Moreover, ceramic wear debris demonstrated the absence of local and systemic toxicity. This makes ceramic bearing particularly suitable for active patients, whatever their age. The results show excellent survival rates of THRs with ceramic components and excellent clinical and radiographic scores with follow-up close to 20 years. However, the excellent outcomes of THRs with ceramic bearings are depending on appropriate and correctly performed surgical technique.

Gastroesophageal reflux disease (GERD) is a chronic common disorder for which patients often refer to specialists. In the last decades, numerous studies helped to clarify the pathophysiology and the natural history of this disease. Currently, in the clinical setting, GERD is defined by the presence of symptoms that, when endoscopic investigation is required, permit to distinguish between cases with or without associated esophageal mucosal injuries. These conditions are called erosive reflux disease and non-erosive reflux disease (NERD), respectively. The latter is the most common manifestation of GERD. Symptoms are defined typical, as heartburn and regurgitation, and atypical (also called extra-esophageal), as coughing and/or wheezing, hoarseness, sore throat, otitis media, and dental manifestations. In this context, it is crucial for clinicians to investigate the presence of features of suspected malignancy, as unexplained weight loss, anemia, dysphagia, persistent vomiting, familiar history of cancer, long history of GERD, and beginning of GERD symptoms after the age of 50 years. The presence of these risk factors should induce to perform an endoscopic examination. Particular attention should be given to functional conditions that can mimic GERD, such as functional heartburn and hypersensitive esophagus as well as, more rarely, eosinophilic esophagitis. The former ones have different pathophysiology and this explains the frequent non-response to proton pump inhibitor drugs. This narrative review provides to clinicians a useful and practical overview of the state-of-the-art on advancements in the knowledge of GERD.

Background:Interstitial lung disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Chest CT is the gold standard in detecting ILD although it is not easy to understand its prognostic value. ILD qualitative assessment is almost worthless. Goh et al. semi quantitative score of ILD extent is related to mortality risk but it is burdened by relevant inter/intra-readers variability. An operator independent algorithm based on voxel-wise analysis proved to identify SSc patients with an increased risk of mortality according to prediction models.Objectives:To verify if quantitative analysis of chest CT (QCT) predict 10 years-mortality in SSc patients.Methods:SSc patients with availability of a chest CT were enrolled in 13 different centers. The CT voxel-wise analysis with a free software (www.horosproject.com) provided QCT indexes: kurtosis, skewness, mean lung attenuation and standard deviation. Patients characteristics, autoimmune profile and pulmonary function test were collected. The follow-up interval lasted from the date of chest CT to the one of the last visit or death. Each QCT index cutoff, established in a previous study (1), clustered patients in two groups. Kaplan-Meier analysis estimated and compared survival in the above mentioned groups. p < 0.05 was considered statistically significant.Results:Five hundred sixty three SSc patients were enrolled (35938 patient-months); 52.4% had ILD detectable at CT scan. For each QCT index cutoff the cohort was split in two subgroups without differences in terms of sex, age, disease duration, autoimmune profile. All QCT indexes’ cutoff selected subgroups with statistically different survival rate (e.g in Figure 1).Figure 1Conclusion:QCT can arise as the new gold standard in identifying SSc patients with poor prognosis. The real possibility to stratify SSc subjects according mortality risk will have a pivotal role in ILD treatment decisional process with the incoming anti-fibrotic drugs.References:[1]Ariani A et al. Rheumatology 2017Disclosure of Interests:Alarico Ariani: None declared, Elena Bravi: None declared, Maria De Santis: None declared, Vanessa Hax: None declared, Simone Parisi: None declared, Federica Lumetti: None declared, Francesco Girelli: None declared, Marta Saracco: None declared, Fabio De Gennaro: None declared, Alessandro Giollo: None declared, Masen Abdel Jaber: None declared, Francesco Bozzao: None declared, Mario Silva: None declared, Maria Chiara Ditto: None declared, Claudia Lomater: None declared, Flavio Mozzani: None declared, Daniele Santilli: None declared, eleonora Di Donato: None declared, Andrea Becciolini Speakers bureau: Sanofi-Genzyme, UCB and AbbVie, Francesco Pucciarini: None declared, Lorenzo Canziani: None declared, Flavio Cesare Bodini: None declared, eugenio arrigoni: None declared, M Bredemeier: None declared, Rafael Mendonça da Silva Chakr: None declared, Amelia Spinella: None declared, Luca Idolazzi: None declared, Roberto Bortolotti: None declared, Paola Tomietto: None declared, Elisa Baratella: None declared, Saverio Tollot: None declared, Dilia Giuggioli: None declared, Fabio Fischetti: None declared, Enrico Fusaro: None declared, Nicola Sverzellati: None declared, Carlo Alberto Scirè: None declared

Les syndromes de compression du nerf ulnaire sont parmi les plus frequents, apres le syndrome du canal carpien. Le nerf ulnaire peut etre comprime a differents niveaux de son trajet donnant des signes et symptomes differents, et les causes peuvent etre tres variees. Les auteurs se sont interesses aux neuropathies exclusivement de type moteur du nerf ulnaire, donc liees a une compression du rameau moteur distal au canal de Guyon ; en particulier les auteurs ont analyse les cas de patients dont la compression est due a des kystes articulaires triquetro-hamatiens ou triquetro-capitals. Les auteurs ont analyse retrospectivement tous les patients presentant une faiblesse progressive ou une paralysie d’au moins un des muscles hypothenars, de l’adductor pollicis ou du flexor pollicis brevis, l’atrophie du premier interosseux en absence de symptomes sensitifs, avec la presence d’un kyste articulaire carpien a l’IRM ou a l’echographie. Les patients ont ete soumis aux tests de Froment, de Wartenberg, de Jeanne et de Masse, et a la version italienne du « Patient rated wrist/hand evaluation » (PRWHE) avant l’intervention chirurgicale et pendant les visites de controle a 15 jours, a 1 mois, a 3 mois, a 6 mois et a 1 an. Les resultats obtenus sont tres variables et dependent de l’âge des patients, de l’etat de sante general mais surtout du temps ecoule entre l’apparition des premiers symptomes et un correct diagnostique, et donc l’intervention chirurgicale. Dans la litterature, tres peu de cas de compression par un kyste de la branche motrice du nerf ulnaire sont decrits, ce qui en fait un syndrome peu connu et qui en consequence est souvent diagnostique en retard. Afin d’accelerer le diagnostic, le traitement, et donc d’obtenir des meilleurs resultats les auteurs soutiennent que les medecins generalistes et specialistes devraient connaitre cette cause de compression du nerf ulnaire distale au canal de Guyon.

Periprosthetic joint infections (PJI) are one of the most dangerous complications in hip surgery. "Two-stage" revision surgery is the treatment of choice. Nevertheless, 5-10% of failures are reported. The aim of this study is to evaluate which factors determine the failure of the two-stage revision in patients affected by hip PJI.We retrospectively enrolled 21 patients treated for hip PJI who had undergone two-stage revision surgery. The diagnosis had been made using criteria established by the Musculoskeletal Infection Society (MSIS) and readapted by the Philadelphia Consensus Conference group. The patients underwent periodic clinical and laboratory controls after the surgical procedure. The two-stage revision treatment was considered unsuccessful in the event of re-infection or in case of severe complications occurring within one year from the treatment.At a mean follow-up of 23.8 months 57% healed with no complications. The reinfection rate was 19% and, after the 3rd stage, the final failure rate was 9.5%. The study has shown, with statistical significance, that a greater number of previous surgical procedures (p0.05, OR=22) and BMI25 (p0.05, OR=4) represent increased risk factors in predicting the failure of two-stage revision surgery. Age, CRP, ESR and a shorter lapse (60 days) between 1st and 2nd stage were recorded in the failure cases, and have to be considered, even if not statistically significant.Knowing the factors responsible for the increased failure of two-stage revision could lead to closer monitoring and more aggressive management in those patients expected to be at greater risk of reinfection. Obesity and multiple surgeries are risk factors for failure.

ObjectivesThis multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease—ILD, emphysema or neither).MethodsChest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. PResultsWe enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (pConclusionsCPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD.

Background:Clinical practice with patients suffering from chronic diseases highlights the presence of psychological symptoms of discomfort fed by biological and non-biological mechanisms linked to disease and treatment. In rheumatic diseases, literature detects the presence of anxious symptoms and depressed mood of clinical and sub-clinical importance with a multifactorial genesis1.Objectives:To detect the impact on the state of health of anxious symptoms and depressed mood in a population suffering from RA and other rheumatic diseases in order to implement the effectiveness of psychological intervention through the selection of patients who present critical levels of discomfort.Methods:Patients afferent to the Rheumatology outpatient clinic of Mauriziano Hospital have been screened from May 2018 to July 2018 with two self-administered questionnaires: HADS-A and HADS-D (Hospital Anxiety and Depression Scale), specifically developed for the evaluation of anxious and depressive symptoms in medical pathologies, and HAQ (Health Assessment Questionnaire) to explore functional disability. Data about rheumatic diagnosis and socio-demographic characteristics were also collected. Data were analyzed with descriptive statistics; the Student Test and the ANOVA test were used to evaluate prevalence and to compare the presentation of symptoms in the different diseases and the Pearson correlation coefficient was used to evaluate the relationship between symptoms and disability.Results:A total of 427 subjects were screened (317 females and 110 males), aged between 19 and 90 years (mean 60 ± 14 yrs). 156 subjects (36.5%) had a diagnosis of RA, 76 (17.8%) of psoriatic arthritis, 42 (9.8%) of ankylosing spondylitis, 14 (3.3%) of systemic lupus erythematosus and 139 (32.6%) of other rheumatic diseases (including Sjogren, osteoarthritis, fibromyalgia).A high prevalence of anxious symptoms and depressed mood has been found and the number of subjects reporting scores indicating a clinically relevant uncomfortable situation (HADS ≥ 11) was also relevant (Table 1); an increased prevalence in female patients was observed. There were no differences in the presentation of symptoms between RA and the other included pathologies (Table 2).Table 1.Prevalence of anxiety and depression according to the HADS questionnaire in rheumatic diseasesMeanSDHADS-A7.564.63HADS-D7.124.59HADS-A ScoreN%0-722452.47-108419.711-2111927.9HADS-D ScoreN%0-723154.17-109221.511-2110424.4Table 2.Comparison between RA and other rheumatic diseases in anxiety and depression symptoms presentation (ANOVA test).NMeanSDSECIHADS-ARA1562.345.200.411.52PsA762.304.470.511.28AS421.513.190.490.51SLE141.773.741.00-0.38other1392.465.080.431.61HADS-DRA1561.743.510.281.19PsA762.034.210.481.07AS420.690.540.080.52SLE140.930.680.180.54other1391.683.790.321.04There was a positive and significant correlation between anxious symptoms or depressed mood and functional disability (0.49 and 0.60 respectively, pConclusion:The results show a significant presence of uncomfortable situations that could evolve in a psychopathological sense. The discomfort expressed through anxious and depressive symptoms is related to the level of functional disability. Recognizing the presence of psychological distress allows to orient the treatment plan and facilitate the patient’s adaptation to the disease condition.References:[1]Geenen R. et al. Best Pract Res Clin Rheumatol. 2012;26(3):305-19.Disclosure of Interests:Gloria Crepaldi Consultant of: Advisory board for Sanofi and Celgene, Speakers bureau: BMS, MSD, Mariarosaria Voci: None declared, Marta Saracco: None declared, Antonella Laezza: None declared, Paolo Santino: None declared, Maddalena Marcato: None declared, Guido Rovera: None declared, Claudia Lomater Consultant of: Advisory board for Sanofi, Novartis, Abbvie

Background: Interstitial Lung Disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Serious lung involvement increase the hospitalization rate and sometimes oxygen therapy is required. An prompt treatment in ILD-SSc patients is essential, but nowadays there is not a feasible method to identify patients with poor prognosis. Although chest Computed Tomography (CT) is the gold standard to detect ILD, there is no standardized assessment of its severity. Quantitative CT (QCT) is an innovative and operator independent method to assess ILD-SSc extent and severity. An increasing number of evidences confirm that QCT is extremely useful for detecting SSc-ILD with the worst prognosis. However is not well established if QCT can predict death or comorbidity associated to ILD. Objectives: The main aim of this study is to verify if QCT predict 8-years mortality or clinical worsening (i.e. hospitalization for respiratory complications or chronic oxygen therapy) in SSc. Methods: Consecutive SSc patients (according to ACR/EULAR classification criteria) from ten different centers underwent a chest CT. Their clinical history was carefully recorded in the following 96 months. A rheumatologist post-analyzed every CT with an open source DICOM viewer in order to obtain QCT indexes. Patients were clustered in two subgroups: according to QCT indexes’ cutoff previously found (see Ariani et al., 2017). The survival time of each patient was considered the time interval between the CT date and death, hospitalization related to lung worsening, beginning of chronic oxygen therapy or last medical examination Results: We enrolled 342 patients; during the 8-years follow-up 15.5% (53/342) died and 4,4% (15/342) had a clinical worsening. The Kaplan-Meier survival analysis demonstrates a worse survival in patients with QCT indexes above or below the previously observed cutoffs. (p References: The QCT indexes’ cutoffs previously found (see Ariani, et al., 2017) identify the SSc-ILD subjects with an high risk of 8-years mortality and comorbidity. These findings suggest that QCT could became a pivotal assessment in SSc management because its role in identifying patients with poor prognosis and who deserve an early aggressive treatment. Disclosure of Interest: None declared

Objective. In this multicentre study, we aimed to evaluate the capacity of a computer-assisted automated QCT method to identify patients with SSc-associated interstitial lung disease (SSc-ILD) with high mortality risk according to validated composite clinical indexes (ILD-Gender, Age, Physiology index and du Bois index). Methods. Chest CT, anamnestic data and pulmonary function tests of 146 patients with SSc were retrospectively collected, and the ILD-Gender, Age, Physiology score and DuBois index were calculated. Each chest CT underwent an operator-independent quantitative assessment performed with a free medical image viewer (Horos). The correlation between clinical prediction models and QCT parameters was tested. A value of P

IBM's Database 2 (DB2) relational database management system (RDBMS) shipped in the early 1980s and drove billions of dollars of revenue to IBM and other firms within its first decade. The product spawned a wealth of add-on tools, shaped the future of mainframe computing, and provided independent software vendors with a strong, reliable, and scalable platform for mission-critical applications. Today, DB2 spans multiple operating systems and is widely deployed across a broad spectrum of industries. This article explores the beginnings of DB2 and traces its rise to prominence.

Objective To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). Methods The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). Results The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti–cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti–tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77–117.39], P = 0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7–152.5], P = 0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2–7.8], P = 0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. Conclusion BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed.

The discovery that the bacterium Helicobacter pylori (H. pylori) lives in the stomach has rendered out-of-date the concept of inhospitality of the gastric environment. H. pylori is able to survive in this organ through mechanisms of acid resistance and colonization factors. The prevalence of H. pylori infection varies depending on age, socioeconomic class, and country. Currently, in the context of a decreased trend in H. pylori prevalence, it is estimated that about 50% of the world's human population are carriers of the microorganism, with a higher rate in developing countries than in developed countries. In this review, the authors provide an overview on the current status of knowledge on the clinical aspects of H. pylori infection, with a focus on diagnostic and therapeutic challenges. In particular, the choice of the test to diagnose H. pylori infection, defined as invasive or non-invasive based on the need or not of biopsy specimens obtained during an endoscopy, depends on the clinical context. Regarding bacterial eradication, it is important that treatment should be decided locally on the basis of local antibiotic usage, documented antibiotic resistance and outcome data. For patients having previously received a clarithromycin-containing regimen, this drug should be avoided as a second-line therapy. In this case, the tailored therapy (to test clarithromycin susceptibility before prescribing drugs) or the so-called quadruple therapy, and triple levofloxacin-based therapy should be proposed. Rifabutin- and furazolidone-based treatments should be reserved for further treatment.

Objective: Predictors of response to biologics in rheumatoid arthritis (RA) is an important issue in the current era. Rituximab (RTX) has been demonstrated effective and safe in active RA, resistant to traditional or biologic DMARDs. Methods: Fifty-seven patients with active longstanding RA were treated with RTX after traditional DMARD or anti- TNF alpha therapy failure. Results: Number of anti-TNF treatment previously failed (p=0.005), HAQ (p=0.013), rheumatoid factor (RF) (p=0.0002) and anti-CCP (p=0.006) were associated with an ACR response ≥50 at the end of 6th month by univariate analysis. Multivariate analysis confirmed that the number of anti-TNF previously failed, baseline HAQ and RF, but not anti-CCP were associated with an ACR response ≥50. EULAR moderate/good response was associated with ESR value (p=0.036), HAQ (p=0.032), and RF (p=0.01) by univariate analysis, while only RF positivity was associated with EULAR moderate/good response by multivariate analysis. Conclusions: RF positivity rather than anti-CCP positivity is a predictor of response to RTX, suggesting that RF-positive patients with low disability may obtain a clinical response when treated to RTX after the first anti-TNF agent failure or after traditional DMARD therapies. Larger studies are required to confirm these results.

Rituximab selectively targets the B-cell compartment, including rheumatoid factor-positive B cells. Short-term efficacy and safety of rituximab in rheumatoid arthritis (RA) has been established by multicenter randomized placebo-controlled studies. Results of long-term follow-up of the phase II/III clinical trials have confirmed the efficacy and safety of repeated courses of rituximab in the responders. However, mechanisms of action in humans, retreatment regimens, biologic effects on memory B cells and on immunoglobulin levels of prolonged exposure of the immune system to B-cell depletion over time, and pharmacogenetic aspects remain open and intriguing issues of rituximab therapy. Several studies are ongoing to clarify possible clinical and biologic predictors of response to rituximab in RA and in other autoimmune diseases where rituximab has been proven to be effective. Preliminary clinical and pharmacogenetic results of our cohort of RA patients managed with rituximab from the year 2000 are presented.

Purpose. Interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary functional tests (PFTs) and semi-quantitative scores based on extent of ILD detectable on chest computed tomography (CT). CT quantitative indexes (QCTIs) are promising tools to assess extent of ILD. This study's aim is to evaluate the validity of QCTI compared with that of chest CT standard evaluation and PFTs. Moreover, QCTI differences between patients subgroups according to prognostic stratifications were investigated. Methods. ILD-SSc of patients from six rheumatological clinics was routinely assessed with chest CT and PFTs. Patients were clustered according to prognosis based on functional and/or radiological examinations. Finally, chest CTs were processed with OsiriX in order to obtain QCTI. Results. Two hundred fifty-seven SSc patients were enrolled. QCTI correlation between extent of ILD and PFTs range from - 0.60 to 0.58 and from - 0.54 to 0.52, respectively. The majority of QCTI have a different distribution in patients subgroups based on prognosis. Most of QCTI discriminate patients with an ILD severity leading to a poor prognosis. Conclusions. QCTI assessment of ILD-SSc is comparable to the evaluation based on chest CT and/or PFTs. QCTI values corresponding to severe ILD were identified. QCTIs are excellent candidates for a new and more reliable SSc-ILD assessment.

Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy).Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days.All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it.Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Information technology architects increasingly find themselves searching for better ways to access, integrate, and leverage their information, applications, and business processes. Information integration, in particular, is critical to the community of Web-based businesses, as firms that are able to leverage their information resources most effectively are best positioned to emerge as leaders in their industries. In this paper, we explore how companies can solve this complex business challenge by extending the reach of WebSphere® technology with DB2® Information Integrator (II). DB2 II offers WebSphere developers a new approach to coping with diverse and distributed information sources, enabling them to reduce programming costs, shorten development cycles, and attain reasonable levels of performance for server-side components that need to integrate information throughout their enterprises and partner networks.

OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p

Background B cells (BC) play a critical role in progressive systemic sclerosis (SS). BC depletion therapy is an attractive option. Objectives to evaluate the efficacy of an intensified B cell depletion therapy in patients with progressive SS Methods Eighteen patients with SS [2 males, mean age 58.33 yrs (46–82)] with severe multiorgan involvement including skin [16], lung, with pulmonary fibrosis (17 patients) and pulmonary hypertension (5), esophagous [9], with polyarthralgias [2] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (4 cases) or as a front line treatment in 14 patients with unsatisfactory therapeutic compliance. IBCDT included: Rituximab (RTX) 375mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given. Results Patients had been followed-up for a mean of 21,67 ± ds 11,05 (06–43) months. Significant decreases (p Conclusions A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding prolonged immunosuppressive therapy particularly appealing. Our data confirm the opportunity to consider the regimens of BL depletion in the treatment of the most severe or refractory forms of SS. Disclosure of Interest None declared

Background Quantitative Computed Tomography (QCT) is an innovative method to assess the severity of interstitial lung disease (ILD) related to systemic sclerosis (SSc). QCT is correlated to semi-quantitative radiological scores (SQs) and functional outcomes (e.g. FVC, DLco, oxygen desaturation after exercise) in SSc patients. However, the autoimmune profile can deeply influence the respiratory system9s involvement. Objectives The main aim of this study is to verify the correlation between SQs, FVC, DLco and QCT in SSc patients clustered according to their autoimmunity. Methods Three hundred three (303) SSc patients were enrolled and underwent functional and radiological assessment. Chest CTs of each patient were evaluated with both SQs and Horos (a software up to perform voxel-wise analysis) in order to obtain QCT indexes. Results Patients were divided in three groups (94 with ACA, 93 with antiScl70, 116 with other autoantibodies). QCT indexes taken into account were kurtosis (Kurt), skewness (Skew), Standard Deviation (SDev), Mean Lung Attenuation (MLA) and fibrosis ratio (FR). Except for the last one, all QCT indexes were assessed both in the parenchymal (pQCT) and in the whole lung (tQCT). The statistically significant (p In ACA patients there are not correlations between DLco and QCT indexes. Conclusions Our results confirm that the majority of QCT indexes are correlated to SQS and functional outcomes. The strongest correlation coefficients were in the antiScl70 subgroup while the weakest ones were in ACA patients. This relevant difference, possibly due to the different prevalence of ILD and type of lung involvement in these two subgroups, should be taken into account when applying the QCT assessment to SSc patients. Disclosure of Interest None declared

ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting.ConclusionThe three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.