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1. Exploring Spatiotemporal Patterns of Cardiovascular Disease in Greece: Insights from the ATTICA Study (2002-2022)

Author

Antigoni Faka, Christos Chalkias, Evangelia Damigou, Christina Chrysohoou, Fotios Barkas, Dimitris Dalmyras, Konstantina Kyrilli, Christos Pitsavos, Evangelos Liberopoulos, Costas Tsioufis, Petros Sfikakis, and Demosthenes Panagiotakos

Subjects
cardiovascular disease, spatial epidemiology, spatial autocorrelation, spatial clustering, Attica, Greece, Geography. Anthropology. Recreation
Abstract

The objective of this study was to investigate spatiotemporal variability of cardiovascular disease (CVD) occurrence and identify spatial clusters on Attica region (Greece), over a 20-year period (2002-2022). The 10- and 20-year occurrence of fatal and non-fatal cardiovascular disease was obtained from the ATTICA study, which was conducted between 2002 and 2022. The sample used in this analysis included 1,935 (49,8% males) and 1,902 participants (49.5% males), respectively. CVD occurrence rate at the municipality level were mapped, and spatial autocorrelation analysis was performed to identify statistically significant clusters and outliers in the Attica region. The mapping of CVD occurrence rates revealed an observable increase in most municipalities during the observation period. In addition, a statistically significant clustering of high CVD occurrence rates was found in the most urbanized municipalities of the study area over the period under study. These findings underscore the need for targeted interventions, focusing on urban populations, to effectively address this trend. Highlights: • This study addresses the research gap on CVD trends in Attica, Greece, over 20 years. • CVD rates rose notably in the most urbanized municipalities of central Athens, while suburban areas maintained lower levels. • Positive spatial autocorrelation analysis was revealed for both the 10-year and 20-year CVD occurrence rates.

Published
2024
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2. Exploratory study of nocebo effect in senior medical students

Author

Charalampos Pischos, Antonios Politis, Petros Sfikakis, and Charalampos Papageorgiou

Subjects
Medicine, Mental healing, RZ400-408
Abstract

# Background Νocebo Effect is known to induce adverse symptoms after negative expectations which can be manifested on a physical and psychological level. As 6th year medical students often face a wide range of clinical challenges and may be prone to negative expectations or beliefs affecting their pre-clinical and clinical success, we want to investigate how they are affected by the Nocebo Effect. # Objective To investigate whether a nocebo effect can be induced when exposing final-year students to the clinical context of their training. # Methods We used verbal suggestions as a nocebo mechanism and by using three tools, the Illness Attitude Scales, the Symptom Checklist-90, and the State-Trait Anxiety Inventory, we examined the difference in scores on measures of psychometric parameters in 33 participants who were on their 6th year medical and attended three clinics for the first time during their education. The administrations were given before and after attending each clinic, and negative verbal suggestions were given prior to the first administration. We also measured whether the overall number of clinics, had an effect on psychometric parameters. # Results The results revealed a significant increase in second administration overall in the three clinics in specific psychometric parameters but no statistically significant difference was observed after attending consecutive clinics. # Conclusion Students reported the occurrence of adverse symptoms in the investigated psychometric parameters, which should be noted in order to avoid potential educational clinical failure.

Published
2024
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3. Single‐cell analysis of MYD88L265P and MYD88WT Waldenström macroglobulinemia patients

Author

Tina Bagratuni, Foteini Aktypi, Ourania Theologi, Maria Sakkou, Kleio Maria Verrou, Nefeli Mavrianou‐Koutsoukou, Dimitrios Patseas, Christine Liacos, Stamatia Skourti, Alexandra Papadimou, Kostantina Taouxi, Foteini Theodorakakou, Georgios Kollias, Petros Sfikakis, Evangelos Terpos, Meletios A. Dimopoulos, and Efstathios Kastritis

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Waldenström macroglobulinemia (WM) is characterized by the expansion of clonal lymphoplasmacytic cells; the MYD88L265P somatic mutation is found in >90% of patients, but malignant B cells may still display intra‐clonal heterogeneity. To assess clonal heterogeneity in WM, we generated and performed single‐cell RNA sequencing of CD19+ sorted cells from five patients with MYD88L265P and two patients with MYD88WT genotype as well as two healthy donors. We identified distinct transcriptional patterns in the clonal subpopulations not only between the two genetically distinct WM subgroups but also among MYD88L265P patients, which affected the B cell composition in the different subgroups. Comparison of clonal and normal/polyclonal B cells within each patient sample enabled the identification of patient‐specific transcriptional changes. We identified gene signatures active in a subset of MYD88L265P patients, while other signatures were active in MYD88WT patients. Finally, gene expression analysis showed common transcriptional features between patients compared to the healthy control but also differentially expressed genes between MYD88L265P and MYD88WT patients involved in distinct pathways, including NFκΒ, BCL2, and BTK. Overall, our data highlight the intra‐tumor clonal heterogeneity in WM with potential prognostic and therapeutic implications.

Published
2024
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4. Molecular Epidemiology of SARS-CoV-2 in Greece Reveals Low Rates of Onward Virus Transmission after Lifting of Travel Restrictions Based on Risk Assessment during Summer 2020

Author

Evangelia Georgia Kostaki, Georgios A. Pavlopoulos, Kleio-Maria Verrou, Giannis Ampatziadis-Michailidis, Vaggelis Harokopos, Pantelis Hatzis, Panagiotis Moulos, Nikolaos Siafakas, Spyridon Pournaras, Christos Hadjichristodoulou, Fani Chatzopoulou, Dimitrios Chatzidimitriou, Periklis Panagopoulos, Panagiota Lourida, Aikaterini Argyraki, Theodoros Lytras, Spyros Sapounas, Gerasimos Gerolymatos, Georgios Panagiotakopoulos, Panagiotis Prezerakos, Sotirios Tsiodras, Vana Sypsa, Angelos Hatzakis, Cleo Anastassopoulou, Nikolaos Spanakis, Athanasios Tsakris, Meletios Athanasios Dimopoulos, Anastasia Kotanidou, Petros Sfikakis, Georgios Kollias, Gkikas Magiorkinis, and Dimitrios Paraskevis

Subjects
Microbiology, QR1-502
Abstract

Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic.

Published
2021
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5. Identifying Country-Level Risk Factors for the Spread of COVID-19 in Europe Using Machine Learning

Author

Serafeim Moustakidis, Christos Kokkotis, Dimitrios Tsaopoulos, Petros Sfikakis, Sotirios Tsiodras, Vana Sypsa, Theoklis E. Zaoutis, and Dimitrios Paraskevis

Subjects
COVID-19, machine learning, data mining, explainability, Microbiology, QR1-502
Abstract

Coronavirus disease 2019 (COVID-19) has resulted in approximately 5 million deaths around the world with unprecedented consequences in people’s daily routines and in the global economy. Despite vast increases in time and money spent on COVID-19-related research, there is still limited information about the factors at the country level that affected COVID-19 transmission and fatality in EU. The paper focuses on the identification of these risk factors using a machine learning (ML) predictive pipeline and an associated explainability analysis. To achieve this, a hybrid dataset was created employing publicly available sources comprising heterogeneous parameters from the majority of EU countries, e.g., mobility measures, policy responses, vaccinations, and demographics/generic country-level parameters. Data pre-processing and data exploration techniques were initially applied to normalize the available data and decrease the feature dimensionality of the data problem considered. Then, a linear ε-Support Vector Machine (ε-SVM) model was employed to implement the regression task of predicting the number of deaths for each one of the three first pandemic waves (with mean square error of 0.027 for wave 1 and less than 0.02 for waves 2 and 3). Post hoc explainability analysis was finally applied to uncover the rationale behind the decision-making mechanisms of the ML pipeline and thus enhance our understanding with respect to the contribution of the selected country-level parameters to the prediction of COVID-19 deaths in EU.

Published
2022
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6. A Deep Learning Framework for Predicting Response to Therapy in Cancer

Author

Theodore Sakellaropoulos, Konstantinos Vougas, Sonali Narang, Filippos Koinis, Athanassios Kotsinas, Alexander Polyzos, Tyler J. Moss, Sarina Piha-Paul, Hua Zhou, Eleni Kardala, Eleni Damianidou, Leonidas G. Alexopoulos, Iannis Aifantis, Paul A. Townsend, Mihalis I. Panayiotidis, Petros Sfikakis, Jiri Bartek, Rebecca C. Fitzgerald, Dimitris Thanos, Kenna R. Mills Shaw, Russell Petty, Aristotelis Tsirigos, and Vassilis G. Gorgoulis

Subjects
Biology (General), QH301-705.5
Abstract

Summary: A major challenge in cancer treatment is predicting clinical response to anti-cancer drugs on a personalized basis. Using a pharmacogenomics database of 1,001 cancer cell lines, we trained deep neural networks for prediction of drug response and assessed their performance on multiple clinical cohorts. We demonstrate that deep neural networks outperform the current state in machine learning frameworks. We provide a proof of concept for the use of deep neural network-based frameworks to aid precision oncology strategies. : Sakellaropoulos et al. designed a machine learning workflow to predict drug response and survival of cancer patients. All pipelines are trained on a large panel of cancer cell lines and tested in clinical cohorts. DNN outperforms other machine learning algorithms by capturing pathways that link gene expression with drug response. Keywords: drug response prediction, precision medicine, machine learning, deep neural networks, DNN

Published
2019
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7. Glomerular Diseases Associated with Malignancies: Histopathological Pattern and Association with Circulating Autoantibodies

Author

Sophia Lionaki, Smaragdi Marinaki, Konstantinos Panagiotellis, Ioanna Tsoumbou, George Liapis, Ioanna Vlahadami, Athanasios Tzioufas, Petros Sfikakis, and Ioannis Boletis

Subjects
glomerular disease, malignancy, solid tumor, lymphoid disorder, outcome, Immunologic diseases. Allergy, RC581-607
Abstract

Aim: Glomerular diseases (GD) associated with malignancies (AM, GDAM) have unique features, which are important to recognize, in the light of the progress made in cancer therapy. We aimed to describe the clinical and histopathological characteristics of patients with GDAM in relation to the presence of circulating autoantibodies, pointing to potential immune pathogenic pathways connecting cancer to GD. Materials and Methods: The included patients were studied retrospectively on the basis of a kidney biopsy proving GD and a related biopsy to establish the diagnosis of AM. We recorded patients’ demographics, serological and laboratory parameters, histopathological findings, and the type of malignancy, GD, and therapy. Results: In total, 41 patients with GDAM, with a mean age of 63.1 (±10.7) years, were studied. In 28 (68.3%) cases, GD was associated with a solid tumor, and in 13 (31.7%) patients with a lymphoid malignancy. The most frequent histopathological pattern was membranous nephropathy (43.9%). Overall, at the time of GD diagnosis, 17% of the patients were positive for antinuclear antibodies (ANA), and 12.2% for antineutrophil cytoplasmic autoantibodies (ANCA), all against myeloperoxidase (MPO). In addition, 93.3% of the patients who had membranous nephropathy were negative for transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) antibody. Sixteen patients (39.0%) presented with acute nephritic syndrome, of whom five (31.25%) developed rapidly progressive glomerulonephritis. In a mean follow-up time of 36.1 (±28.3) months, nine (21.95%) patients ended up with end-stage kidney disease, and eight (19.5%) died. Conclusion: We found that 3.2% of patients who underwent a native kidney biopsy in our institution during the past decade, for any reason, were identified as having some type of GD associated with a malignancy. Serology indicated a significant presence of ANA or MPO-ANCA antibodies in patients with nephritic syndrome and the absence of PLA2R antibodies in patients with membranous nephropathy.

Published
2020
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8. P25 24-HOUR AORTIC AMBULATORY BLOOD PRESSURE IS BETTER ASSOCIATED WITH COMMON CAROTID ARTERY HYPERTROPHY THAN 24-HOUR BRACHIAL PRESSURE – THE SAFAR STUDY

Author

Antonios Argyris, Evaggelia Aissopou, Efthymia Nasothymiou, Theodoros Papaioannou, Jacques Blacher, Michel Safar, Petros Sfikakis, and Athanase Protogerou

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective: Evidence suggests the superiority of office aortic pressure over brachial on the evaluation of vascular damage and prognosis of cardiovascular disease (CVD); 24-hour ambulatory blood pressure monitoring (ABPM) is regarded the optimal method for assessing blood pressure (BP) profile. The non-invasive 24-hour aortic ABPM is feasible and superior to 24-hour brachial regarding the association with left ventricular hypertrophy and diastolic dysfunction. The aim of our study was to examine the association of 24-hour aortic and brachial ABPM with common carotid artery (CCA) hypertrophy. Methods: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ABPM using a validated oscillometric brachial cuff-based devise (Mobil-O-Graph). CCA hypertrophy was assessed by high-resolution ultrasound (assessment of intima media thickness - IMT). Results: 497 subjects (aged 54 ± 13 years, 57% men, 80% hypertensives) were examined. Using Hotelling’s-Williams test it was shown that 24-hour aortic BP was significantly better correlated with IMT as compared with brachial BP (r: 0,254 vs. r: 0,202 for right IMT, r: 0,244 vs. r: 0,207 for left IMT, p < 0,05). Multivariate analysis (adjusted for possible confounders) revealed superiority of 24-hour aortic BP regarding the association with IMT as well as carotid hypertrophy. Last, in ROC analysis, aortic BP had a higher discriminatory ability compared to brachial for the detection of carotid hypertrophy (AUC: 0,707 vs. 0,656 for right carotid artery hypertrophy, AUC: 0,636 vs. 0,602 for left carotid artery hypertrophy, p < 0,05). Conclusions: Non-invasively assessed 24-hour aortic pressure is more strongly associated with CCA IMT and provides a higher discriminatory ability for the detection of CCA hypertrophy.

Published
2018
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9. 3.4 A CLINICAL SCORE TO PREDICT ELEVATED ARTERIAL STIFFNESS: DERIVATION AND VALIDATION IN 3,943 HYPERTENSIVE PATIENTS

Author

Panagiotis Xaplanteris, Charalambos Vlachopoulos, Athanasios Protogerou, Konstantinos Aznaouridis, Dimitris Terentes-Printzios, Antonis Argyris, Nikolaos Tentolouris, Petros Sfikakis, and Dimitris Tousoulis

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Purpose/Background/Objectives: Aortic stiffness assessed by carotid-femoral pulse wave velocity (PWV) is an important predictor to gauge the overall risk of hypertensive patients; nonetheless, it is underutilized in everyday practice. We derived a simple scoring system based on clinical variables that can identify patients with a priority for measurement of PWV, i.e. those with elevated PWV (≥ 10 m/sec) and at higher risk for events. Methods: Patient data from three outpatient clinics (n = 3,943) were used to form a derivation, internal and external validation cohort. For derivation, independent predictors of high PWV from a binary logistic regression model were dichotomized and implemented in a clinical prediction scoring system with the acronym SAGE (office systolic blood pressure ≥160 mmHg: 4 points, age ≥ 60 years: 4 points, glycemia [blood glucose ≥126 mg/dl]: 1 point, eGFR ≤60: 2 points). Results: Its performance was validated at the internal and external validation cohorts with c-statistics being 0.781 (95% CI: 0.753–0.808) and 0.718 (95% CI: 0.682–0.755) respectively (Figure 1). A cut-off of 5 points to identify patients with high PWV in the external validation cohort yielded a positive predictive value, negative predictive value, sensitivity and specificity of 60.7%, 84.8%, 51.9% and 78.3% respectively. Conclusions: The SAGE score that takes into account easily measured clinical variables (systolic blood pressure, age, glucose and eGFR) can be used to predict elevated levels of PWV and prioritize its measurement in specific patients. Its use will result in greater acknowledgement of the role of aortic stiffness and aid physicians in implementing it in clinical practice.

Published
2018
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11. Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model

Author

Alexandru Garaiman 1, Klaus Steigmiller 2, Catherine Gebhard 3, Carina Mihai 1, Rucsandra Dobrota 1, Cosimo Bruni 4, Marco Matucci-Cerinic 5, Joerg Henes 6, Jeska de Vries-Bouwstra 7, Vanessa Smith 8, Andrea Doria 9, Yannick Allanore 10, Lorenzo Dagna 11, Branimir Anić 12, Carlomaurizio Montecucco 13, Otylia Kowal-Bielecka 14, Mickael Martin 15, Yoshiya Tanaka 16, Anna-Maria Hoffmann-Vold 17, Ulrike Held 2, Oliver Distler 1, Mike Oliver Becker 1, EUSTAR Silvia Bellando Randone, Gemma Lepri, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Ewa Gindzienska-Sieskiewicz, Katarzyna Karaszewska, Maurizio Cutolo, Giovanna Cuomo, Elise Siegert, Simona Rednic, Jérome Avouac, Carole Desbas, Roberto Caporali, Lorenzo Cavagna, Patricia E Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J Kucharz, Elisabetta Zanatta, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstr, Mislav Radic, Alexandra Balbir-Gurman, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Nemanja Damjanov, Ann-Christian Pecher, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Ivan Foeldvari, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Lidia P Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Carlos de la Puente, Øyvind Midtvedt, Torhild Garen, Håvard Fretheim, Eric Hachulla, Valeria Riccieri, Ruxandra Maria Ionescu, Ana Maria Gheorghiu, Cord Sunderkötter, Jörg Distler, Francesca Ingegnoli, Luc Mouthon, Francesco Paolo Cantatore, Susanne Ullman, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Marko Baresic, Miroslav Mayer, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Alessandra Vacca, Kamal Solanki, Douglas Veale, Esthela Loyo, Carmen Tineo, Mengtao Li, Edoardo Rosato, Fahrettin Oksel, Figen Yargucu, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Marzena Olesinska, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jorge Juan Gonzalez Martin, Jean Sibilia, Ira Litinsky, Francesco Del Galdo, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianch, Breno Valdetaro Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M Hsu, Thierry Martin, Sergey Moiseev, Pavel Novikov, Lorinda S Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Gabriela Riemekasten, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Daniel Furst, Ana-Maria Ramazan, H U Scherer, Tom W J Huizinga, Marie-Elise Truchetet, Alain Lescoat, Giacomo De Luca, Corrado Campochiaro, J M van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Cédric L, Mathieu Puyade, Pascal Roblot, Satoshi Kubo, Yasuyuki Todoroki, 1, Alexandru Garaiman, 2, Klaus Steigmiller, 3, Catherine Gebhard, 1, Carina Mihai, 1, Rucsandra Dobrota, 4, Cosimo Bruni, 5, Marco Matucci-Cerinic, 6, Joerg Hene, 7, Jeska de Vries-Bouwstra, 8, Vanessa Smith, 9, Andrea Doria, Allanore 10, Yannick, Dagna 11, Lorenzo, Anić 12, Branimir, Montecucco 13, Carlomaurizio, Kowal-Bielecka 14, Otylia, Martin 15, Mickael, Tanaka 16, Yoshiya, Hoffmann-Vold 17, Anna-Maria, 2, Ulrike Held, 1, Oliver Distler, 1, Mike Oliver Becker, Silvia Bellando Randone, Eustar, Lepri, Gemma, Walker, Ulrich, Iannone, Florenzo, Jordan, Suzana, Becvar, Radim, Gindzienska-Sieskiewicz, Ewa, Karaszewska, Katarzyna, Cutolo, Maurizio, Cuomo, Giovanna, Siegert, Elise, Rednic, Simona, Avouac, Jérome, Desbas, Carole, Caporali, Roberto, Cavagna, Lorenzo, E Carreira, Patricia, Novak, Srdan, Czirják, László, Iudici, Michele, J Kucharz, Eugene, Zanatta, Elisabetta, Coleiro, Bernard, Moroncini, Gianluca, Farge Bancel, Dominique, Airò, Paolo, Hesselstr, Roger, Radic, Mislav, Balbir-Gurman, Alexandra, Hunzelmann, Nicola, Pellerito, Raffaele, Giollo, Alessandro, Morovic-Vergles, Jadranka, Denton, Christopher, Damjanov, Nemanja, Pecher, Ann-Christian, Ortiz Santamaria, Vera, Heitmann, Stefan, Krasowska, Dorota, Hasler, Paul, Foeldvari, Ivan, João Salvador, Maria, Stamenkovic, Bojana, Francesco Selmi, Carlo, P Ananieva, Lidia, Herrick, Ariane, Müller-Ladner, Ulf, DE PALMA, Raffaele, Engelhart, Merete, Szücs, Gabriela, de la Puente, Carlo, Midtvedt, Øyvind, Garen, Torhild, Fretheim, Håvard, Hachulla, Eric, Riccieri, Valeria, Maria Ionescu, Ruxandra, Maria Gheorghiu, Ana, Sunderkötter, Cord, Distler, Jörg, Ingegnoli, Francesca, Mouthon, Luc, Paolo Cantatore, Francesco, Ullman, Susanne, Rosa Pozzi, Maria, Eyerich, Kilian, Wiland, Piotr, Vanthuyne, Marie, Jose Alegre-Sancho, Juan, Herrmann, Kristine, De Langhe, Ellen, Baresic, Marko, Mayer, Miroslav, Yavuz, Sule, Granel, Brigitte, de Souza Müller, Carolina, Agachi, Svetlana, Stebbings, Simon, Mathieu, D'Alessandro, Vacca, Alessandra, Solanki, Kamal, Veale, Dougla, Loyo, Esthela, Tineo, Carmen, Li, Mengtao, Rosato, Edoardo, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Foti, Rosario, Ancuta, Codrina, Maurer, Britta, van Laar, Jacob, Olesinska, Marzena, Kayser, Cristiane, Fathi, Nihal, García de la Peña Lefebvre, Paloma, Juan Gonzalez Martin, Jorge, Sibilia, Jean, Litinsky, Ira, Del Galdo, Francesco, Ann Saketkoo, Lesley, Kerzberg, Eduardo, Bianch, Washington, Valdetaro Bianchi, Breno, Castellví, Ivan, Limonta, Massimiliano, Rimar, Doron, Couto, Maura, Spertini, Françoi, Marcoccia, Antonella, Kahl, Sarah, M Hsu, Ivien, Martin, Thierry, Moiseev, Sergey, Novikov, Pavel, S Chung, Lorinda, Schmeiser, Tim, Majewski, Dominik, Zdrojewski, Zbigniew, Martínez-Barrio, Julia, Bernardino, Vera, Riemekasten, Gabriela, Levy, Yair, Rezus, Elena, Nuri Pamuk, Omer, Sarzi Puttini, Piercarlo, Poormoghim, Hadi, Kötter, Ina, Gaches, Franci, Belloli, Laura, Sfikakis, Petro, Furst, Daniel, Ramazan, Ana-Maria, U Scherer, H, J Huizinga, Tom W, Truchetet, Marie-Elise, Lescoat, Alain, De Luca, Giacomo, Campochiaro, Corrado, M van Laar, J, Rudnicka, Lidia, Oliveira, Susana, Atzeni, Fabiola, Kuwana, Masataka, Mekinian, Arsene, L, Cédric, Puyade, Mathieu, Roblot, Pascal, Kubo, Satoshi, Todoroki, Yasuyuki, and University of Zurich

Subjects
prognostic prediction model, Rheumatology, 10051 Rheumatology Clinic and Institute of Physical Medicine, digital ulcers, platelets inhibitors, 610 Medicine & health, Pharmacology (medical), SSc, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI)
Abstract

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Published
2022
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12. Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from the EUSTAR cohort

Author

Elisabetta Zanatta 1, Dörte Huscher 2, Augusta Ortolan 1, Jérôme Avouac 3, Paolo Airò 4, Alexandra Balbir-Gurman 5, Elise Siegert 6, Marco Matucci Cerinic 7, Franco Cozzi 8, Gabriela Riemekasten 9, Anna-Maria Hoffmann-Vold 10, Oliver Distler 11, Armando Gabrielli 12, Stefan Heitmann 13, Nicolas Hunzelmann 14, Carlomaurizio Montecucco 15, Jadranka Morovic-Vergles 16, Camillo Ribi 17, Andrea Doria 1, Yannick Allanore 3, EUSTAR collaborators, Giovanna Cuomo, Gianluca Moroncini, Jiri Stork, Fiorenzo Iannone, Ulrich Walker, Eugenia Bertoldo, Dorota Krasowska, Maria João Salvador, Mohammed Tikly, Eric Hachulla, Valeria Riccieri, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Branimir Anic, Maria Üprus, Brigitte Granel, Alessandra Vacca, Cristina-Mihaela Tanaseanu, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Lesley Ann Saketkoo, Eduardo Kerzberg, Massimiliano Limonta, Doron Rimar, Petros Sfikakis, Maurizio Cutolo, Patricia E Carreira, Rosario Foti, Srdan Novak, Michele Iudici, Mislav Radic, Raffaele Pellerito, Carlo Francesco Selmi, Lidia P Ananieva, Gabriela Szücs, Carlos de la Puente, Ruxandra Maria Ionescu, Jörg Distler, Maria Rosa Pozzi, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Sule Yavuz, Carolina de Souza Müller, Svetlana Agachi, Douglas Veale, Esthela Loyo, Mengtao Li, Edoardo Rosato, Britta Maurer, Ivan Castellví, François Spertini, Kamal Solanki, Nicoletta Del Papa, Gerard Espinosa, László Czirják, Bernard Coleiro, Dominique Farge Bancel, Christopher Denton, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Michaela Kohm, Bojana Stamenkovic, 1, Elisabetta Zanatta, 2, Dörte Huscher, 1, Augusta Ortolan, 3, Jérôme Avouac, 4, Paolo Airò, 5, Alexandra Balbir-Gurman, 6, Elise Siegert, 7, Marco Matucci Cerinic, 8, Franco Cozzi, 9, Gabriela Riemekasten, Hoffmann-Vold 10, Anna-Maria, Distler 11, Oliver, Gabrielli 12, Armando, Heitmann 13, Stefan, Hunzelmann 14, Nicola, Montecucco 15, Carlomaurizio, Morovic-Vergles 16, Jadranka, Ribi 17, Camillo, 1, Andrea Doria, 3, Yannick Allanore, Collaborators, Eustar, Cuomo, Giovanna, Moroncini, Gianluca, Stork, Jiri, Iannone, Fiorenzo, Walker, Ulrich, Bertoldo, Eugenia, Krasowska, Dorota, João Salvador, Maria, Tikly, Mohammed, Hachulla, Eric, Riccieri, Valeria, Sha, Ami, Maria Gheorghiu, Ana, Sunderkötter, Cord, Ingegnoli, Francesca, Mouthon, Luc, Smith, Vanessa, Paolo Cantatore, Francesco, Eyerich, Kilian, Wiland, Piotr, Vanthuyne, Marie, Anic, Branimir, Üprus, Maria, Granel, Brigitte, Vacca, Alessandra, Tanaseanu, Cristina-Mihaela, García de la Peña Lefebvre, Paloma, Sibilia, Jean, Litinsky, Ira, Ann Saketkoo, Lesley, Kerzberg, Eduardo, Limonta, Massimiliano, Rimar, Doron, Sfikakis, Petro, Cutolo, Maurizio, E Carreira, Patricia, Foti, Rosario, Novak, Srdan, Iudici, Michele, Radic, Mislav, Pellerito, Raffaele, Francesco Selmi, Carlo, P Ananieva, Lidia, Szücs, Gabriela, de la Puente, Carlo, Maria Ionescu, Ruxandra, Distler, Jörg, Rosa Pozzi, Maria, Jose Alegre-Sancho, Juan, Herrmann, Kristine, De Langhe, Ellen, Yavuz, Sule, de Souza Müller, Carolina, Agachi, Svetlana, Veale, Dougla, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Maurer, Britta, Castellví, Ivan, Spertini, Françoi, Solanki, Kamal, Del Papa, Nicoletta, Espinosa, Gerard, Czirják, László, Coleiro, Bernard, Farge Bancel, Dominique, Denton, Christopher, Damjanov, Nemanja, Henes, Jörg, Ortiz Santamaria, Vera, Kohm, Michaela, and Stamenkovic, Bojana

Subjects
interstitial lung disease, Scleroderma, Systemic, Hypertension, Pulmonary, disease subset, anti-topoisomerase I, Scleroderma, Systemic sclerosis, cutaneous form, outcome, Phenotype, Rheumatology, Scleroderma, Limited, Antibodies, Antinuclear, Scleroderma, Diffuse, Humans, Pharmacology (medical), Lung Diseases, Interstitial
Abstract

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Published
2022
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13. P254 Secukinumab retention and safety in patients with active psoriatic arthritis or ankylosing spondylitis: two-year interim results of the observational SERENA study

Author

Karl Gaffney, Uta Kiltz, Petros Sfikakis, Nicola Gullick, Athina Theodoridou, Jan Brandt-Juergens, Eric Lespessailles, Juanzhi Fang, Effie Pournara, Barbara Schulz, and Piotr Jagiello

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Background/Aims SERENA is an ongoing, prospective, non-interventional study evaluating retention, effectiveness, safety/tolerability and quality of life in > 2,900 patients with moderate to severe plaque psoriasis, active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) treated with secukinumab at 438 sites across Europe for up to 5 years. We present interim results reporting secukinumab treatment retention and safety data through two years in PsA and AS patients. Methods This interim analysis presents data from 534 PsA and 470 AS patients enrolled (target population fulfilling eligibility criteria) and followed for at least two years. Patients (≥18 years) with active PsA or AS should have received at least 16 weeks secukinumab treatment before enrolment in the study. Retention rate was defined as percentage of patients who did not discontinue secukinumab treatment. Treatment break was defined as interruption of therapy for at least three months after last injection. Results The mean treatment duration prior to enrolment in the study was 1.0 year and 0.91 year for PsA and AS, respectively. The retention rates for secukinumab after one year since enrolment and since initiation of treatment were: PsA, 85.2% (n = 519, CI: 82.01-88.32) and 96.8% (n = 528, CI: 95.18-98.38); AS, 85.8% (n = 452, CI: 82.52-89.17) and 94.2% (n = 464, CI: 91.94-96.42), respectively. After two years since enrolment and since initiation of treatment, the retention rates were: PsA, 74.9% (n = 498, CI: 70.99-78.81) and 87.0% (n = 515, CI: 83.99-89.99); AS, 78.9% (n = 437, CI: 75.01-82.88) and 84.8% (n = 454, CI: 81.39-88.21), respectively. At baseline, the majority of PsA (79.5%; n/N=423/532) patients were receiving secukinumab 300 mg, while 97.0% (n/N=456/470) of AS patients were receiving secukinumab 150 mg. The majority of patients continued their initial secukinumab dose; “no dose change” in secukinumab treatment was reported after one and two years in the study (year one: PsA, 93.4% [n = 499] and AS, 92.6% [n = 435]; year two: PsA, 89.7% [n = 479] and AS, 87.9% [n = 413]). Secukinumab treatment break was recorded for 31 PsA patients (median [min, max] treatment break duration in days: 125.0 [61-461]) and for 42 AS patients (118.0 [61-813]), mainly due to adverse events reported in 58.1% (n = 18) and 45.2% (n = 19) of patients, respectively. The retreatment started with monthly dosing in most of the cases: PsA, 80.6% (n/N=25/31) and AS, 76.2% (n/N=32/42). No new or unexpected safety signals were reported. Conclusion Secukinumab retention rates in a real-world setting after more than two years since initiation of treatment and after two years since study enrolment indicate high persistence rates. Safety data collected prospectively for up to two years confirm the favorable safety profile of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Gilead, MSD, Novartis, UCB, Pfizer. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. A. Theodoridou: Consultancies; UCB, Amgen, Novartis. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. E. Lespessailles: Consultancies; Amgen, Expanscience, Lilly, MSD. Member of speakers’ bureau; Amgen, Expanscience, Lilly, MSD. Grants/research support; Abbvie, Amgen, Lilly, MSD, UCB,. J. Fang: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Published
2022
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14. P268 Impact of intermediate treatment interruption on secukinumab efficacy in patients with active psoriatic arthritis and ankylosing spondylitis: interim analysis results from the SERENA study

Author

Karl Gaffney, Uta Kiltz, Petros Sfikakis, Nicola Gullick, Gkikas Katsifis, Anna Kandili, Jan Brandt-Juergens, Phillipe Goupille, Nicola Maiden, Maher Aassi, Barbara Schulz, Effie Pournara, and Piotr Jagiello

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in > 2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in ≥ 2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs; 18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4]; n = 6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1]; n = 2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7]; n = 5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. G. Katsifis: Consultancies; Abbvie, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, Sobi, UCB. Honoraria; AbbVie, Aenorasis, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, UCB. A. Kandili: None. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Janssen. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. P. Goupille: Consultancies; AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Biogen, BMS, Chugai, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. N. Maiden: Member of speakers’ bureau; Eli-Lilly, UCB. M. Aassi: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Published
2022
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15. Consensus on the assessment of systemic sclerosis–associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment

Author

Cosimo Bruni, Maya H Buch, Aleksandra Djokovic, Giacomo De Luca, Raluca B Dumitru, Alessandro Giollo, Ilaria Galetti, Alexia Steelandt, Konstantinos Bratis, Yossra Atef Suliman, Ivan Milinkovic, Anna Baritussio, Ghadeer Hasan, Anastasia Xintarakou, Yohei Isomura, George Markousis-Mavrogenis, Sophie Mavrogeni, Luna Gargani, Alida LP Caforio, Carsten Tschöpe, Arsen Ristic, Sven Plein, Elijah Behr, Yannick Allanore, Masataka Kuwana, Christopher P Denton, Daniel E Furst, Dinesh Khanna, Thomas Krieg, Renzo Marcolongo, Alessia Pepe, Oliver Distler, Petros Sfikakis, Petar Seferovic, and Marco Matucci-Cerinic

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Published
2023
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16. Real-Life Outcome of Lupus Nephritis with Current Therapies: Study Protocol of a Multicentre Observational Study

Author

Antonis Fanouriakis, Maria Tektonidou, George Bertsias, Dimitrios Boumpas, Petros Sfikakis, Prodromos Sidiropoulos, Dimitrios Vassilopoulos, Alexandros Garyfallos, Charalampos Papagoras, Pinelopi Konstantopoulou, Kyriaki Boki, Antonia Elezoglou, Maria Kosmetatou, and Maria Pappa

Subjects
Rheumatology
Abstract

Lupus nephritis (LN) affects a significant proportion of patients with systemic lupus erythematosus (SLE) and is characterised by increased morbidity and mortality. The updated joint EULAR/European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations for the management of LN have set as target of therapy the optimisation (preservation or improvement) of kidney function, accompanied by a reduction in proteinuria of at least 25% by 3 months, 50% by 6 months, and below 500-700 mg/g by 12 months (complete clinical response). It is currently unknown what proportion of Greek patients with LN reach these proposed targets with the current available treatments. At the same time, recent successful phase 3 trials have led to the approval of both belimumab and voclosporin for the treatment of patients with LN and have steered discussions as to whether the "induction-maintenance" paradigm should be substituted by an early combination treatment for all patients. To inform future therapeutic decisions and facilitate the positioning of these new drugs in the therapeutic algorithm of LN, the current study protocol aims to map the unmet needs in the treatment of LN in Greece, by quantifying the proportion of patients who attain the recommended treatment targets in everyday clinical practice.

Published
2022

17. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Author

Muriel Elhai, Nanthara Sritharan, Marouane Boubaya, Alexandra Balbir-Gurman, Elise Siegert, Eric Hachulla, Jeska de Vries-Bouwstra, Gabriela Riemekasten, Jörg H W Distler, Edoardo Rosato, Francesco Del Galdo, Fabian A Mendoza, Daniel E Furst, Carlos de la Puente, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Oliver Distler, Coralie Bloch-Queyrat, Yannick Allanore, Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Otylia Kowal Bielecka, Maurizio Cutolo, Giovanna Cuomo, Claudia Kedor, Simona Rednic, Jérome Avouac, P. Vlachoyiannopoulos, C. Montecucco, Jiri Stork, Murat Inanc, Patricia E. Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Elisabetta Zanatta, Katja Perdan-Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstrand, Mislav Radic, Yolanda Braun-Moscovici, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Madelon Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Kohm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P. Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Cristina Sobrino Grande, Øyvind Midtvedt, David Launay, Valeria Riccieri, Ruxandra Maria Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Joanna Busquets, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Percival D. Sampaio-Barros, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Mengtao Li, Walid Ahmed Abdel Atty Mohamed, Antonietta Gigante, Fahrettin Oksel, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Giuseppina Abignano, Goda Seskute, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M. Hsu, Thierry Martin, Sergey Moiseev, Lorinda S. Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Sabine Sommerlatte, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Juliana Markus, Gary R Feldman, Ana-Maria Ramazan, H.U. Scherer, Marie-Elise Truchetet, Alain Lescoat, Lorenzo Dagna, J.M. van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Mickaël Martin, Yoshiya Tanaka, Elhai, M., Sritharan, N., Boubaya, M., Balbir-Gurman, A., Siegert, E., Hachulla, E., de Vries-Bouwstra, J., Riemekasten, G., Distler, J. H. W., Rosato, E., Del Galdo, F., Mendoza, F. A., Furst, D. E., de la Puente, C., Hoffmann-Vold, A. -M., Gabrielli, A., Distler, O., Bloch-Queyrat, C., Allanore, Y., Matucci Cerinic, M., Walker, U., Iannone, F., Jordan, S., Becvar, R., Kowal Bielecka, O., Cutolo, M., Cuomo, G., Kedor, C., Rednic, S., Avouac, J., Vlachoyiannopoulos, P., Montecucco, C., Stork, J., Inanc, M., Carreira, P. E., Novak, S., Czirjak, L., Iudici, M., Kucharz, E. J., Zanatta, E., Perdan-Pirkmajer, K., Coleiro, B., Moroncini, G., Farge Bancel, D., Airo, P., Hesselstrand, R., Radic, M., Braun-Moscovici, Y., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Giollo, A., Morovic-Vergles, J., Denton, C., Vonk, M., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Hasler, P., Kohm, M., Foeldvari, I., Bajocchi, G., Salvador, M. J., Stamenkovic, B., Selmi, C. F., Tikly, M., Ananieva, L. P., Herrick, A., Muller-Ladner, U., De Palma, R., Engelhart, M., Szucs, G., Sobrino Grande, C., Midtvedt, O., Launay, D., Riccieri, V., Ionescu, R. M., Sha, A., Gheorghiu, A. M., Sunderkotter, C., Ingegnoli, F., Mouthon, L., Smith, V., Cantatore, F. P., Ullman, S., Alberto von Muhlen, C., Pozzi, M. R., Eyerich, K., Wiland, P., Vanthuyne, M., Alegre-Sancho, J. J., Herrmann, K., De Langhe, E., Anic, B., Uprus, M., Yavuz, S., Granel, B., de Souza Muller, C., Busquets, J., Agachi, S., Stebbings, S., Mathieu, D. A., Sampaio-Barros, P. D., Stamp, L., Solanki, K., Veale, D., Loyo, E., Li, M., Abdel Atty Mohamed, W. A., Gigante, A., Oksel, F., Tanaseanu, C. -M., Foti, R., Ancuta, C., Maurer, B., van Laar, J., Kayser, C., Fathi, N., Garcia de la Pena Lefebvre, P., Sibilia, J., Litinsky, I., Abignano, G., Seskute, G., Saketkoo, L. A., Kerzberg, E., Bianchi, W., Castellvi, I., Limonta, M., Rimar, D., Couto, M., Spertini, F., Marcoccia, A., Kahl, S., Hsu, I. M., Martin, T., Moiseev, S., Chung, L. S., Schmeiser, T., Majewski, D., Zdrojewski, Z., Martinez-Barrio, J., Bernardino, V., Sommerlatte, S., Levy, Y., Rezus, E., Nuri Pamuk, O., Sarzi Puttini, P., Poormoghim, H., Kotter, I., Gaches, F., Belloli, L., Sfikakis, P., Markus, J., Feldman, G. R., Ramazan, A. -M., Scherer, H. U., Truchetet, M. -E., Lescoat, A., Dagna, L., van Laar, J. M., Rudnicka, L., Oliveira, S., Atzeni, F., Kuwana, M., Mekinian, A., Martin, M., and Tanaka, Y.

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Published
2022

18. Microwave Radiometry for the Diagnosis and Monitoring of Inflammatory Arthritis

Author

Katerina Laskari, Elias Siores, Maria Tektonidou, and Petros Sfikakis

Subjects
Clinical Biochemistry
Abstract

The ability of microwave radiometry (MWR) to detect with high accuracy in-depth temperature changes in human tissues is under investigation in various medical fields. The need for non-invasive, easily accessible imaging biomarkers for the diagnosis and monitoring of inflammatory arthritis provides the background for this application in order to detect the local temperature increase due to the inflammatory process by placing the appropriate MWR sensor on the skin over the joint. Indeed, a number of studies reviewed herein have reported interesting results, suggesting that MWR is useful for the differential diagnosis of arthritis as well as for the assessment of clinical and subclinical inflammation at the individual large or small joint level and the patient level. MWR showed higher agreement with musculoskeletal ultrasound, used as a reference, than with clinical examination in rheumatoid arthritis (RA), while it also appeared useful for the assessment of back pain and sacroiliitis. Further studies with a larger number of patients are warranted to confirm these findings, taking into account the current limitations of the available MWR devices. This may lead to the production of easily accessible and inexpensive MWR devices that will provide a powerful impetus for personalized medicine.

Published
2023
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20. Pulmonary Arterial Hypertension in Connective Tissue Disorders: The emerging role of screening and early diagnosis. A position paper for Greek Rheumatologists

Author

Eftychia Demerouti, Iraklis Tsangaris, Theodoros Dimitroulas, George Giannakoulas, Pelagia Katsimpri, Ioanna Mitrouska, Stylianos Orfanos, Ioannis Skoularigkis, Paraskevi Voulgari, and Petros Sfikakis

Subjects
lcsh:Diseases of the musculoskeletal system, scleroderma, Review, lcsh:RC925-935, Pulmonary arterial hypertension, connective tissue disorders
Abstract

Pulmonary Arterial Hypertension is regarded as a devastating disease, complicating Connective Tissue Diseases. Although much progress has been achieved in the last 20 years, several unfulfilled needs in diagnosis and management of PAH in these patients may still be identified. After a systematic review of the literature and integrating results from the latest research articles, key clinical issues for the screening and diagnosis of Pulmonary Arterial Hypertension in Connective Tissue Disorder Patients and specifically Scleroderma patients are described in this article, allowing physicians to contribute to early diagnosis of patients with Scleroderma-associated Pulmonary Arterial Hypertension.

Published
2019

24. Significant weight loss in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Author

Michael Hughes, Calvin Heal, Elise Siegert, Eric Hachulla, Paolo Airó, Antonella Riccardi, Oliver Distler, Marco Matucci-Cerinic, Andrea Doria, Lorenzo Baretta, Alexandra Balbir-Gurman, Patricia E Carreira, Vanessa Smith, Carlos Alberto, Jörg Distler von Mühlen, Ulf Müller-Ladner, Lidia P Ananieva, László Czirják, Jörg Henes, Jeska de Vries-Bouwstra, Mengtao Li, Fabian Mendoza, Nemanja Damjanov, Ivan Castellví, Alessandro Giollo, Stefan Heitmann, Edoardo Rosato, Lorenzo Dagna, Christopher P Denton, Marie Vanthuyne, Fabio Cacciapaglia, Valeria Riccieri, Nicolas Hunzelmann, Ami Shah, Carlomaurizio Montecucco, Raffaele Pellerito, Ruxandra Maria Ionescu, Simona Rednic, Ulrich Walker, Maria Rosa Pozzi, Anna-Maria Hoffmann-Vold, Marie-Elise Truchetet, Susanne Ullman, Carolina de Souza Müller, Juan Jose Alegre-Sancho, Eduardo Kerzberg, Francesco Del Galdo, Gabriela Riemekasten, Branimir Anic, Marko Baresic, Miroslav Mayer, Fahrettin Oksel, Figen Yargucu, Ellen De Langhe, Ina Kötter, Mohammed Tikly, Radim Becvar, Douglas Veale, Dorota Krasowska, Andrea Lo Monaco, Lidia Rudnicka, Ana Maria Gheorghiu, Piercarlo Sarzi Puttini, Mislav Radic, Armando Gabrielli, Maria João Salvador, Carlos de la Puente, Gabriela Szücs, Sule Yavuz, Rosario Foti, Otylia Kowal Bielecka, Codrina Ancuta, Peter Villiger, Sabine Adler, Patrick Jego, Michaela Kohm, Eugene J Kucharz, Dominique Farge Bancel, Tim Schmeiser, Alberto Cauli, Alessandra Vacca, Kamal Solanki, Piotr Wiland, Paloma García de la Peña Lefebvre, Jorge Juan Gonzalez Martin, Sergio Jimenez, Lesley Ann Saketkoo, Roger Hesselstrand, Francesca Ingegnoli, Jean Sibilia, Merete Engelhart, Esthela Loyo, Carmen Tineo, Francesco Paolo Cantatore, Brigitte Krummel-Lorenz, Petros Sfikakis, Cristiane Kayser, Vera Ortiz Santamaria, Bojana Stamenkovic, Giovanna Cuomo, Francesco Puppo, Thierry Zenone, Nihal Fathi, Ira Litinsky, Carlo Chizzolini, Monika Swacha, Washington Bianchi, Breno Valdetaro Bianchi, Maria Üprus, Kati Otsa, Masataka Kuwana, Panayiotis Vlachoyiannopoulos, Sarah Kahl, Bernard Coleiro, François Spertini, Walid Ahmed Abdel Atty Mohamed, Sergey Moiseev, Pavel Novikov, Dominik Majewski, Simon Stebbings, Svetlana Agachi, Massimiliano Limonta, Carlo Francesco Selmi, Elena Rezus, Kristine Herrmann, Brigitte Granel, Goda Seskute, Matthias Seidel, Paul Hasler, Maurizio Cutolo Vera Bernardino, Carmen Pizzorni, Jadranka Morovic-Vergles, Daniel Furst, Ana-Maria Ramazan, Gianluigi Bajocchi, Lisa Stamp, Doron Rimar, Antonella Marcoccia, Srdan Novak, Luc Mouthon, Jiri Stork, Lorinda S Chung, Hadi Poormoghim, Francis Gaches, Laura Belloli, Cristina-Mihaela Tanaseanu, Fabiola Atzeni, Kilian Eyerich, Ivien M Hsu, Jacob van Laar, Mary Ellen Csuka, Omer Nuri Pamuk, Maura Couto, Arsene Mekinian, Murat Inanc, Ivan Foeldvari, Julia Martínez-Barrio, Yair Levy, Juliana Markus, Susana Oliveira, Hughes, Michael, Heal, Calvin, Siegert, Elise, Hachulla, Eric, Airó, Paolo, Riccardi, Antonella, Distler, Oliver, Matucci-Cerinic, Marco, Doria, Andrea, Baretta, Lorenzo, Balbir-Gurman, Alexandra, E Carreira, Patricia, Smith, Vanessa, Alberto, Carlo, Distler von Mühlen, Jörg, Müller-Ladner, Ulf, P Ananieva, Lidia, Czirják, László, Henes, Jörg, de Vries-Bouwstra, Jeska, Li, Mengtao, Mendoza, Fabian, Damjanov, Nemanja, Castellví, Ivan, Giollo, Alessandro, Heitmann, Stefan, Rosato, Edoardo, Dagna, Lorenzo, P Denton, Christopher, Vanthuyne, Marie, Cacciapaglia, Fabio, Riccieri, Valeria, Hunzelmann, Nicola, Shah, Ami, Montecucco, Carlomaurizio, Pellerito, Raffaele, Maria Ionescu, Ruxandra, Rednic, Simona, Walker, Ulrich, Rosa Pozzi, Maria, Hoffmann-Vold, Anna-Maria, Truchetet, Marie-Elise, Ullman, Susanne, de Souza Müller, Carolina, Jose Alegre-Sancho, Juan, Kerzberg, Eduardo, Del Galdo, Francesco, Riemekasten, Gabriela, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Oksel, Fahrettin, Yargucu, Figen, De Langhe, Ellen, Kötter, Ina, Tikly, Mohammed, Becvar, Radim, Veale, Dougla, Krasowska, Dorota, Lo Monaco, Andrea, Rudnicka, Lidia, Maria Gheorghiu, Ana, Sarzi Puttini, Piercarlo, Radic, Mislav, Gabrielli, Armando, João Salvador, Maria, de la Puente, Carlo, Szücs, Gabriela, Yavuz, Sule, Foti, Rosario, Kowal Bielecka, Otylia, Ancuta, Codrina, Villiger, Peter, Adler, Sabine, Jego, Patrick, Kohm, Michaela, J Kucharz, Eugene, Farge Bancel, Dominique, Schmeiser, Tim, Cauli, Alberto, Vacca, Alessandra, Solanki, Kamal, Wiland, Piotr, García de la Peña Lefebvre, Paloma, Juan Gonzalez Martin, Jorge, Jimenez, Sergio, Ann Saketkoo, Lesley, Hesselstrand, Roger, Ingegnoli, Francesca, Sibilia, Jean, Engelhart, Merete, Loyo, Esthela, Tineo, Carmen, Paolo Cantatore, Francesco, Krummel-Lorenz, Brigitte, Sfikakis, Petro, Kayser, Cristiane, Ortiz Santamaria, Vera, Stamenkovic, Bojana, Cuomo, Giovanna, Puppo, Francesco, Zenone, Thierry, Fathi, Nihal, Litinsky, Ira, Chizzolini, Carlo, Swacha, Monika, Bianchi, Washington, Valdetaro Bianchi, Breno, Üprus, Maria, Otsa, Kati, Kuwana, Masataka, Vlachoyiannopoulos, Panayioti, Kahl, Sarah, Coleiro, Bernard, Spertini, Françoi, Ahmed Abdel Atty Mohamed, Walid, Moiseev, Sergey, Novikov, Pavel, Majewski, Dominik, Stebbings, Simon, Agachi, Svetlana, Limonta, Massimiliano, Francesco Selmi, Carlo, Rezus, Elena, Herrmann, Kristine, Granel, Brigitte, Seskute, Goda, Seidel, Matthia, Hasler, Paul, Cutolo Vera Bernardino, Maurizio, Pizzorni, Carmen, Morovic-Vergles, Jadranka, Furst, Daniel, Ramazan, Ana-Maria, Bajocchi, Gianluigi, Stamp, Lisa, Rimar, Doron, Marcoccia, Antonella, Novak, Srdan, Mouthon, Luc, Stork, Jiri, S Chung, Lorinda, Poormoghim, Hadi, Gaches, Franci, Belloli, Laura, Tanaseanu, Cristina-Mihaela, Atzeni, Fabiola, Eyerich, Kilian, M Hsu, Ivien, van Laar, Jacob, Ellen Csuka, Mary, Nuri Pamuk, Omer, Couto, Maura, Mekinian, Arsene, Inanc, Murat, Foeldvari, Ivan, Martínez-Barrio, Julia, Levy, Yair, Markus, Juliana, and Oliveira, Susana

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, weight loss, systemic sclerosis, nutrition, Immunology, Disease, computer.software_genre, General Biochemistry, Genetics and Molecular Biology, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Weight loss, Internal medicine, Weight Loss, Epidemiology, medicine, Humans, Immunology and Allergy, 610 Medicine & health, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, Database, business.industry, Middle Aged, medicine.disease, 030104 developmental biology, Mood, Databases as Topic, Female, Outcomes research, medicine.symptom, business, computer, Rheumatism
Abstract

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Published
2020
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26. Healthcare policy in Ancient Greece

Author

Marianna Karamanou Gregory Tsoucalas Theodore G Papaioannou Petros Sfikakis

Subjects
Health Sciences, Επιστήμες Υγείας
Published
2019

27. Inhalt Band 31, 2008

Author

Eftychia Kafantari, Lambros Kordelas, Theodoros N. Sergentanis, Nadya Ziv-Sokolovsky, Hanoch Kashtan, Svetlana Machlenkin, Aphrodite Nonni, Michael Dinerman, Christos Papadimitriou, Maria Sotiropoulou, Morio Ohtsuka, Petros Sfikakis, Konstantinos Dimitrakakis, Irene Dimitriadis, Effstratios Patsouris, Chunyan Wang, Uta Dirksen, Ahmet Elmaagacli, Michael Paulussen, Emel Yaman, John Bramis, Xiaojing Tong, Ali Osman Kaya, Meletios A. Dimopoulos, Sebastian Pieper, Aristidis Diamantis, Efraim Idelevich, Banu Ozturk, Kensuke Nakazawa, Ekmel Tezel, Stavros Dimopoulos, Michael Koldehoff, Gabriele Braun-Munzinger, Edgar Jost, Sinan Sozen, Ran Reshef, Donald E. Tsai, Jianhua Zheng, Suleyman Buyukberber, George H. Sakorafas, Andreas H. Mahnken, Liankun Li, Liying Cai, Reinhard Osieka, Panagiota Kontogianni, Michael Bendel, George Androutsos, Nikolaos V. Michalopoulos, Qi You, Heribert Jürgens, Konstantinos Mandrekas, Martina Crysandt, Emmanouil Magiorkinis, Flora Zagouri, Stefan Wilop, Dietrich W. Beelen, George C. Zografos, Mustafa Benekli, Baruch Brenner, Ramazan Yildiz, Rudolf Trenschel, Dimitra Koulocheri, Ugur Coskun, Victor Buyevich, Hiroaki Satoh, Andreas Ranft, Kiyohisa Sekizawa, and Deniz Yamac

Subjects
Cancer Research, Oncology, Hematology
Published
2008
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28. Contents Vol. 31, 2008

Author

Deniz Yamac, Qi You, Maria Sotiropoulou, Heribert Jürgens, Martina Crysandt, Stefan Wilop, Chunyan Wang, Michael Paulussen, Victor Buyevich, George H. Sakorafas, Liankun Li, Hiroaki Satoh, Michael Dinerman, Nadya Ziv-Sokolovsky, Konstantinos Mandrekas, Ali Osman Kaya, Emel Yaman, Ran Reshef, Stavros Dimopoulos, John Bramis, Sinan Sozen, Suleyman Buyukberber, Sebastian Pieper, Banu Ozturk, Andreas H. Mahnken, Hanoch Kashtan, Aphrodite Nonni, Svetlana Machlenkin, Michael Bendel, George C. Zografos, Dietrich W. Beelen, Lambros Kordelas, Morio Ohtsuka, Edgar Jost, Mustafa Benekli, Baruch Brenner, Andreas Ranft, Konstantinos Dimitrakakis, Meletios A. Dimopoulos, Xiaojing Tong, Ramazan Yildiz, Rudolf Trenschel, George Androutsos, Jianhua Zheng, Reinhard Osieka, Kiyohisa Sekizawa, Flora Zagouri, Efraim Idelevich, Christos Papadimitriou, Emmanouil Magiorkinis, Petros Sfikakis, Effstratios Patsouris, Kensuke Nakazawa, Nikolaos V. Michalopoulos, Uta Dirksen, Michael Koldehoff, Eftychia Kafantari, Irene Dimitriadis, Ahmet Elmaagacli, Donald E. Tsai, Theodoros N. Sergentanis, Ekmel Tezel, Dimitra Koulocheri, Ugur Coskun, Aristidis Diamantis, Panagiota Kontogianni, Gabriele Braun-Munzinger, and Liying Cai

Subjects
Cancer Research, Oncology, Hematology
Published
2008
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29. Subject Index Vol. 31, 2008

Author

Theodoros N. Sergentanis, Edgar Jost, Michael Dinerman, Jianhua Zheng, Deniz Yamac, Stavros Dimopoulos, Kiyohisa Sekizawa, Dietrich W. Beelen, Suleyman Buyukberber, Lambros Kordelas, John Bramis, Ahmet Elmaagacli, Meletios A. Dimopoulos, Andreas Ranft, Xiaojing Tong, Sinan Sozen, Ran Reshef, Emel Yaman, George Androutsos, Sebastian Pieper, Banu Ozturk, Nadya Ziv-Sokolovsky, Michael Koldehoff, Andreas H. Mahnken, Chunyan Wang, Svetlana Machlenkin, Michael Paulussen, Christos Papadimitriou, Qi You, Martina Crysandt, Ali Osman Kaya, Heribert Jürgens, Victor Buyevich, Efraim Idelevich, Petros Sfikakis, Donald E. Tsai, Eftychia Kafantari, Reinhard Osieka, Hiroaki Satoh, Liying Cai, Kensuke Nakazawa, Nikolaos V. Michalopoulos, Irene Dimitriadis, Stefan Wilop, Konstantinos Mandrekas, Michael Bendel, Maria Sotiropoulou, Effstratios Patsouris, Ekmel Tezel, Morio Ohtsuka, Konstantinos Dimitrakakis, Uta Dirksen, Dimitra Koulocheri, Ugur Coskun, Flora Zagouri, George C. Zografos, Mustafa Benekli, Baruch Brenner, Gabriele Braun-Munzinger, Hanoch Kashtan, Aphrodite Nonni, Panagiota Kontogianni, George H. Sakorafas, Liankun Li, Aristidis Diamantis, Emmanouil Magiorkinis, Ramazan Yildiz, and Rudolf Trenschel

Subjects
Cancer Research, Index (economics), Oncology, Statistics, Subject (documents), Hematology, Mathematics
Published
2008
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30. Sachwortverzeichnis Band 31, 2008

Author

George Androutsos, Nikolaos V. Michalopoulos, Michael Bendel, John Bramis, Sebastian Pieper, Banu Ozturk, Eftychia Kafantari, George C. Zografos, Emmanouil Magiorkinis, Mustafa Benekli, Baruch Brenner, Victor Buyevich, Effstratios Patsouris, Martina Crysandt, Hiroaki Satoh, Michael Dinerman, Michael Koldehoff, Aristidis Diamantis, Andreas H. Mahnken, Deniz Yamac, Maria Sotiropoulou, Stefan Wilop, Donald E. Tsai, Reinhard Osieka, Dimitra Koulocheri, Liying Cai, Ugur Coskun, Sinan Sozen, Ran Reshef, Meletios A. Dimopoulos, Xiaojing Tong, Emel Yaman, Dietrich W. Beelen, Morio Ohtsuka, Konstantinos Dimitrakakis, Chunyan Wang, Michael Paulussen, Theodoros N. Sergentanis, Nadya Ziv-Sokolovsky, Ali Osman Kaya, Efraim Idelevich, Kensuke Nakazawa, Lambros Kordelas, Uta Dirksen, Andreas Ranft, Ekmel Tezel, Ramazan Yildiz, Rudolf Trenschel, Stavros Dimopoulos, Suleyman Buyukberber, Qi You, Heribert Jürgens, Konstantinos Mandrekas, Ahmet Elmaagacli, Edgar Jost, Jianhua Zheng, Hanoch Kashtan, Aphrodite Nonni, Christos Papadimitriou, Petros Sfikakis, Irene Dimitriadis, George H. Sakorafas, Liankun Li, Kiyohisa Sekizawa, Panagiota Kontogianni, Gabriele Braun-Munzinger, Svetlana Machlenkin, and Flora Zagouri

Subjects
Cancer Research, Oncology, Hematology
Published
2008
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32. Fatal Bleeding Disorder as the First Manifestation of a Giant Aortic Aneurysm

Author

Petros Sfikakis, Angelos Evangelopoulos, and Natalia G. Vallianou

Subjects
Disseminated intravascular coagulation, medicine.medical_specialty, Exacerbation, business.industry, Consumption Coagulopathy, medicine.disease, Surgery, Conservative treatment, Aortic aneurysm, Aneurysm, medicine.artery, cardiovascular system, medicine, Thoracic aorta, Radiology, Nuclear Medicine and imaging, Radiology, Chronic disseminated intravascular coagulation, business
Abstract

Aortic aneurysms are a rare cause of consumption coagulopathy. We describe an 82-year old woman with a previously unrecognized giant aneurysm of the thoracic aorta. The first manifestation of this condition was hemoptysis that was due to an exacerbation of chronic disseminated intravascular coagulation. The patient eventually died despite intensive conservative treatment, as she declined late surgical intervention. This case underscores the need to exclude aortic aneurysms by performing a chest X-ray in elderly patients with bleeding disorders.

Published
2009
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33. Elective laparoscopic splenectomy for giant hemangioma: a case report

Author

Georgios Anthimidis, Kalliopi Vasiliadou, Petros Sfikakis, N. Tziris, Marios Grigoriou, Epaminondas Fahantidis, Christophoros Kosmidis, and Christopher Efthimiadis

Subjects
Medicine(all), medicine.medical_specialty, business.industry, medicine.medical_treatment, Splenectomy, Case Report, Splenic Neoplasm, Giant Hemangioma, Spleen, General Medicine, medicine.disease, Laparoscopic splenectomy, Asymptomatic, Surgery, Hemangioma, medicine.anatomical_structure, medicine, Splenic Hemangioma, medicine.symptom, business
Abstract

Although unusual, hemangioma is the most common primary splenic neoplasm. Splenectomy is indicated when the tumor is large, with increased risk of hemorrhage. The laparoscopic approach is preferred for most elective splenectomies. Although technically feasible, laparoscopic splenectomy can be a challenge in the patient with splenomegaly. We present herein a case of an 18-year-old male asymptomatic patient who underwent laparoscopic splenectomy for the incidental finding of splenomegaly caused by a large splenic hemangioma. Laparoscopic splenectomy appears to be a safe and effective procedure, in appropriately experienced hands, for patients with splenomegaly, given the spleen's fragile anatomy and its relationship to other abdominal viscera.

Published
2009
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34. Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Author

Elias, Gialafos J. Ioannis, Moyssakis Theodora, Psaltopoulou and Dimitrios, Papadopoulos P. Despoina, Perea Kostantinos, Vlasis and Charalampos, Kostopoulos Vassilios, Votteas Petros, Sfikakis P.

Subjects
integumentary system
Abstract

Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n = 69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P = .03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc. Copyright (c) 2008 Gialafos J. Elias et al.

Published
2008

35. DGHO fordert verbesserte Bedingungen für die Durchführung nicht-kommerzieller Studien

Author

Eftychia Kafantari, Efraim Idelevich, John Bramis, Effstratios Patsouris, Sebastian Pieper, Banu Ozturk, Emel Yaman, Stavros Dimopoulos, Dietrich W. Beelen, Suleyman Buyukberber, Dimitra Koulocheri, Reinhard Osieka, Meletios A. Dimopoulos, Ugur Coskun, Panagiota Kontogianni, Qi You, Sinan Sozen, Ran Reshef, Heribert Jürgens, Michael Koldehoff, Michael Bendel, Xiaojing Tong, Christos Papadimitriou, Maria Sotiropoulou, Donald E. Tsai, Martina Crysandt, Petros Sfikakis, Konstantinos Mandrekas, Victor Buyevich, Morio Ohtsuka, Konstantinos Dimitrakakis, Hiroaki Satoh, Emmanouil Magiorkinis, Flora Zagouri, Aristidis Diamantis, Svetlana Machlenkin, Irene Dimitriadis, Gabriele Braun-Munzinger, Stefan Wilop, Andreas Ranft, Edgar Jost, George Androutsos, Kiyohisa Sekizawa, Michael Dinerman, Jianhua Zheng, Nadya Ziv-Sokolovsky, Uta Dirksen, Ahmet Elmaagacli, Nikolaos V. Michalopoulos, Theodoros N. Sergentanis, Ekmel Tezel, George C. Zografos, Mustafa Benekli, Baruch Brenner, Ramazan Yildiz, Rudolf Trenschel, Chunyan Wang, Michael Paulussen, Ali Osman Kaya, Kensuke Nakazawa, Lambros Kordelas, George H. Sakorafas, Liankun Li, Hanoch Kashtan, Aphrodite Nonni, Deniz Yamac, Andreas H. Mahnken, and Liying Cai

Subjects
Cancer Research, Oncology, Hematology
Published
2008
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36. Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Author

Elias, Gialafos J., primary, Ioannis, Moyssakis, additional, Theodora, Psaltopoulou, additional, Dimitrios, Papadopoulos P., additional, Despoina, Perea, additional, Kostantinos, Vlasis, additional, Charalampos, Kostopoulos, additional, Vassilios, Votteas, additional, and Petros, Sfikakis P., additional

Published
2008
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37. A data mining framework for predicting drug response in cancer

Author

Konstantinos Vougas, Theodore Sakelaropoulos, Filippos Koinis, Alexander Polyzos, Athanassios Kotsinas, Vassilis Myrianthopoulos, Moss, Tyler J., Sarina Piha-Paul, Hua Zhou, Sonali Narang, Foukas, George-Romanos P., Andreas Ntargaras, Vassilis Georgoulias, Leonidas Alexopoulos, Iannis Aifantis, Paul Townsend, Petros Sfikakis, Rebecca Fitzgerald, Dimitris Thanos, Mills Shaw, Kenna R., Jiri Bartek, Russell Petty, Aristotelis Tsirigos, and Vasileios Gorgoulis

Subjects
Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc
Abstract

Defining therapeutically “vulnerable” genes that modulate anti-cancer drug response is of paramount importance in precision cancer treatment. The success of such a task largely depends on the ability to develop computational resources that integrate big “omic” data into effective drug-response models. Herein, based on the pharmacogenomic profile of 1,001 cancer cell lines we constructed a novel in silico screening process based on Association Rule Mining for identifying genes as candidate drivers of drug response. Our computational pipeline explores with high efficiency large sample-spaces, is able to detect low frequency events and evaluate statistical significance even in the multidimensional space, presenting the results in the form of easily interpretable rules. The selection algorithm was validated by in silico and experimental means. Within this context, we identified experimentally novel targets related with responsiveness to: i) Doxorubicin treatment, and ii) MAPK and PI3K inhibitor administration. The presented data mining scheme provides evidence for potential practical applications and a proof-of-concept for the implementation of precision medicine in everyday clinical practice.

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