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1. Evaluation of the cytochrome P450 2C19 and 3A4 inhibition potential of the complement factor 5a receptor 1 antagonist ACT‐1014‐6470 in vitro and in vivo

Author

Marion Anliker‐Ort, Jasper Dingemanse, Stephane Delahaye, Luboš Janů, John van denAnker, Benjamin Berger, and Priska Kaufmann

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Abstract ACT‐1014‐6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto‐inflammatory diseases. The in vitro inhibition potential of ACT‐1014‐6470 on cytochrome P450 isozymes (CYPs) and its effect on the pharmacokinetics (PK) of the CYP2C19 and CYP3A4 substrates omeprazole and midazolam, respectively, in humans were assessed. In vitro assays were conducted with isoform‐specific substrates in human liver microsomes. In an open‐label, two‐period, fixed‐sequence cocktail study, single doses of 20 mg omeprazole and 2 mg midazolam were administered concomitantly to 20 healthy male subjects alone (treatment A) and after a single dose of 100 mg ACT‐1014‐6470 (treatment B) under fed conditions. Safety and PK assessments were performed. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of noncompartmental PK parameters of treatment B versus treatment A were calculated. In vitro, no time‐dependent inhibition was observed and the lowest inhibition constant of 4.3 μM ACT‐1014‐6470 was recorded for CYP2C19. In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5–2.5) for maximum plasma concentration (Cmax) and 1.9 (1.5–2.3) for area under the plasma concentration‐time curve from 0 to 12 h (AUC0‐12 h). Midazolam PK showed GMRs (90% CI) of 1.1 (1.1–1.2) for Cmax and 1.5 (1.4–1.6) for AUC0‐24 h. All treatments were well‐tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT‐1014‐6470 reflected a weak inhibition of CYP2C19 and CYP3A4.

Published
2023
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2. Influence of hepatic impairment on the pharmacokinetics and pharmacodynamics of the P2Y12 receptor antagonist selatogrel

Author

Uta Schilling, Chih‐Hsuan Hsin, Stephane Delahaye, Andreas Krause, Hauke Wuelfrath, Atef Halabi, and Jasper Dingemanse

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Abstract Selatogrel is a potent and selective reversible P2Y12 receptor antagonist in development for early treatment of acute myocardial infarction via subcutaneous (s.c.) self‐injection. Selatogrel is almost exclusively eliminated via the hepatobiliary route. Hepatic impairment is associated with reduced drug clearance and primary hemostasis. This single‐center, open‐label study investigated the effect of mild and moderate hepatic impairment on pharmacokinetics (PK) and pharmacodynamics (PD) of a single s.c. dose of selatogrel (16 mg). The study included groups of eight subjects with mild and moderate hepatic impairment, and matched healthy control subjects. Compared to healthy subjects, exposure to selatogrel in subjects with mild and moderate hepatic impairment was 30% and 108% (maximum plasma concentration [Cmax]) and 47% and 212% (area under the concentration‐time curve from zero to infinity [AUC0–∞]) higher, respectively. Hepatic impairment was associated with lower clearance and volume of distribution, whereas plasma protein binding was not affected. Marked inhibition of platelet aggregation (IPA > 80%) was attained within 30 min in all subjects and hepatic impairment prolonged IPA duration. Area under the effect curve was 60% and 160% higher in subjects with mild and moderate hepatic impairment, respectively. PK/PD modeling identified a change in the relationship between exposure and IPA, with a steeper concentration‐effect relationship in healthy subjects compared to subjects with hepatic impairment. The combination of higher exposure and lower half‐maximum inhibitory concentration resulted in longer lasting effect. In conclusion, hepatic impairment alters the PK/PD relationship leading to prolonged effects. Therefore, dose adjustments may be warranted in subjects with moderate hepatic impairment.

Published
2022
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3. An open‐label, nonrandomized, phase Ib feasibility study of cusatuzumab in patients with nasopharyngeal carcinoma

Author

Astrid De Meulenaere, Tijl Vermassen, David Creytens, Stijn De Keukeleire, Tim Delahaye, Philippe Deron, Fréderic Duprez, Samson Fung, Patrick Pauwels, Liesbeth Ferdinande, and Sylvie Rottey

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Abstract CD70 is expressed in up to 80% of nasopharyngeal carcinoma (NPC) cases. Cusatuzumab is a humanized anti‐CD70 monoclonal antibody, with dual action mechanisms: induction of cytotoxicity against CD70+ tumor cells and reduction in CD70‐CD27 signaling mediated immune evasion. The aim of this study was to assess the safety, pharmacokinetic profile, immunogenicity, pharmacodynamic profile, and preliminary activity of cusatuzumab in advanced NPC. Eleven patients were enrolled: one patient was assigned to arm A (adjuvant cusatuzumab monotherapy after curative chemoradiation), nine patients to arm B (cusatuzumab monotherapy; noncurative setting), and one patient to arm C (cusatuzumab + chemotherapy; noncurative setting); irrespective of tumoral CD70 expression. Both patients in arms A and C completed the study. All patients in arm B discontinued at an early stage. Five patients experienced grade greater than or equal to 3 nondrug related treatment‐emergent adverse events, most commonly fatigue and pneumonia (18%). An infusion‐related reaction was observed in two of 11 patients. Laboratory results showed no trend over time. Seven patients were eligible for response evaluation. No objective response to cusatuzumab was observed with stable disease being the best response. The current study indicates that the safety profile of cusatuzumab (with or without concurrent chemotherapy) is manageable in patients with advanced NPC, which is consistent with known safety profile. Limited activity of cusatuzumab in advanced NPC was observed. Combination therapies of cusatuzumab and other types of therapy should be explored for the improvement of activity in NPC and other CD70‐expressing malignancies.

Published
2021
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4. Prevalence of low health literacy levels in decompensated heart failure compared with acute myocardial infarction patients

Author

Adèle Perrin, Gergis Abdalla, Marie Viprey, François Delahaye, Nathan Mewton, Michel Ovize, Laurent Sebbag, Thomas Bochaton, Alexandra L. Dima, Estelle Bravant, Anne‐Marie Schott, and Julie Haesebaert

Subjects
Cardiovascular diseases, Heart failure, Myocardial infarction, Health literacy, Epidemiology, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Health literacy (HL) is a health determinant in cardiovascular diseases as the active participation of patients is essential for optimizing self‐management of these conditions. We aimed to estimate the prevalence of low HL level in patients hospitalized for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and explore low HL determinants. Methods and results A prospective cross‐sectional study was performed in three cardiology units. HL level was assessed using Brief Health Literacy Screen (BHLS) and categorized as low or adequate. Dimensions of HL were assessed with the Health Literacy Questionnaire (HLQ). Associations with sociodemographic factors, disease history, and comorbidities were explored. A total of 208 patients were included, mean ± SD age was 68.5 ± 14.9 years, and 65.9% were men. Patients with ADHF were significantly older and more often women than AMI patients. Prevalence of low HL was 36% overall, 51% in ADHF patients, and 21% in AMI patients (P

Published
2021
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5. TRIAL21: A COHORT OF ADULTS WITH DOWN SYNDROME AT RISK OF DEVELOPING ALZHEIMER'S DISEASE

Author

Rebillat, Anne‐Sophie, primary, Laffon De Mazieres, Clarisse, additional, Hiance‐Delahaye, Anne, additional, Baraton, Caroline, additional, Bourgerie, Anne‐Sophie, additional, Bourgeois, Pauline, additional, Clert, Manon, additional, Falquero, Segolene, additional, Martet, Diane, additional, Sacco, Silvia, additional, Vilaire, Marie, additional, Durand, Sophie, additional, and Mircher, Clotilde, additional

Published
2023
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7. Integrated systems‐genetic analyses reveal a network target for delaying glioma progression

Author

Liisi Laaniste, Prashant K. Srivastava, Julianna Stylianou, Nelofer Syed, Silvia Cases‐Cunillera, Kirill Shkura, Qingyu Zeng, Owen J. L. Rackham, Sarah R. Langley, Andree Delahaye-Duriez, Kevin O'Neill, Matthew Williams, Albert Becker, Federico Roncaroli, Enrico Petretto, and Michael R. Johnson

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Objective To identify a convergent, multitarget proliferation characteristic for astrocytoma transformation that could be targeted for therapy discovery. Methods Using an integrated functional genomics approach, we prioritized networks associated with astrocytoma progression using the following criteria: differential co‐expression between grade II and grade III IDH1‐mutated and 1p/19q euploid astrocytomas, preferential enrichment for genetic risk to cancer, association with patient survival and sample‐level genomic features. Drugs targeting the identified multitarget network characteristic for astrocytoma transformation were computationally predicted using drug transcriptional perturbation data and validated using primary human astrocytoma cells. Results A single network, M2, consisting of 177 genes, was associated with glioma progression on the basis of the above criteria. Functionally, M2 encoded physically interacting proteins regulating cell cycle processes and analysis of genome‐wide gene‐regulatory interactions using mutual information and DNA–protein interactions revealed the known regulators of cell cycle processes FoxM1, B‐Myb, and E2F2 as key regulators of M2. These results suggest functional disruption of M2 via gene mutation or altered expression as a convergent pathway regulating astrocytoma transformation. By considering M2 as a multitarget drug target regulating astrocytoma transformation, we identified several drugs that are predicted to restore M2 expression in anaplastic astrocytoma toward its low‐grade profile and of these, we validated the known antiproliferative drug resveratrol as down‐regulating multiple nodes of M2 including at nanomolar concentrations achievable in human cerebrospinal fluid by oral dosing. Interpretation Our results identify M2 as a multitarget network characteristic for astrocytoma progression and encourage M2‐based drug screening to identify new compounds for preventing glioma transformation.

Published
2019
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9. The endothelin receptor antagonist macitentan for the treatment of pulmonary arterial hypertension: A cross‐species comparison of its cytochrome P450 induction pattern

Author

Alexander Treiber, Stephane Delahaye, Swen Seeland, and Carmela Gnerre

Subjects
endothelin receptor antagonist, macitentan, P450 induction, species differences, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract The dual endothelin receptor antagonist macitentan was approved in 2013 for the treatment of pulmonary arterial hypertension. Macitentan is an inducer of cytochrome P450 expression in vivo in animal species but not in man. In rat and dog, changes in P450 expression manifest as autoinduction upon repeat dosing. The induction pattern, however, significantly differed between both species, and between male and female rats. While macitentan exposure steadily declined with dose in the dog, P450 induction was saturable in the rat reaching levels of 40%‐60% and 60%‐80% at steady‐state in male and female animals, respectively. The nature and number of P450 enzymes involved in macitentan clearance were identified as a major reason for the observed species differences. In the dog, macitentan was metabolized by a single P450 enzyme, that is, Cyp3a12, whereas several members of the Cyp2c and Cyp3a families were involved in the rat. Macitentan selectively upregulated Cyp3a expression in rat, whereas the expression of the Cyp2c enzymes involved in macitentan metabolism remained mostly unchanged, eventually leading to a higher contribution of Cyp3a upon induction. Macitentan also induced CYP3A4 expression in human hepatocytes via initial activation of the human pregnane X receptor. No such induction was evident in humans at the therapeutic macitentan dose of 10 mg as shown in a clinical drug‐drug interaction study with the CYP3A4 substrate sildenafil.

Published
2020
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12. Evaluation of the cytochrome <scp>P450 2C19</scp> and <scp>3A4</scp> inhibition potential of the complement factor 5a receptor 1 antagonist <scp>ACT</scp> ‐1014‐6470 in vitro and in vivo

Author

Marion Anliker‐Ort, Jasper Dingemanse, Stephane Delahaye, Luboš Janů, John van den Anker, Benjamin Berger, and Priska Kaufmann

Subjects
General Neuroscience, General Medicine, General Pharmacology, Toxicology and Pharmaceutics, General Biochemistry, Genetics and Molecular Biology
Published
2023

15. Cusatuzumab for treatment of CD70‐positive relapsed or refractory cutaneous T‐cell lymphoma

Author

Leupin, Nicolas, Zinzani, Pier Luigi, Morschhauser, Franck, Dalle, Stephane, Maerevoet, Marie, Michot, Jean-Marie, Ribrag, Vincent, Offner, Fritz, Beylot-Barry, Marie, Moins-Teisserenc, Helene, Zwaenepoel, Karen, De Winne, Koen, Battistella, Maxime, Hultberg, Anna, Gandini, Domenica, Moshir, Mahan, Jacobs, Julie, Delahaye, Tim, Khan, Aitzaz, Zabrocki, Piotr, Silence, Karen, van Rompaey, Luc, Borg, Christophe, Motta, Giovanna, Melle, Federica, Calleri, Angelica, Pauwels, Patrick, de Haard, Hans, Pileri, Stefano, Bagot, Martine, and de Winne, Koen

Subjects
Cancer Research, medicine.medical_specialty, Skin Neoplasms, Antineoplastic Agents, Gastroenterology, Pharmacokinetics, Refractory, Internal medicine, medicine, Humans, Adverse effect, business.industry, Immunogenicity, Cutaneous T-cell lymphoma, Antibodies, Monoclonal, medicine.disease, Lymphoma, T-Cell, Cutaneous, Lymphoma, Clinical trial, Treatment Outcome, Oncology, Human medicine, Neoplasm Recurrence, Local, Vasculitis, business, CD27 Ligand
Abstract

Background The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL). Methods In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed. Results The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sezary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses. Conclusions Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development.

Published
2021

16. Treatment Efficacy and Compliance in Patients with Diabetic Macular Edema Treated with Ranibizumab in a Real-Life Setting

Author

Anne-Laurence Best, Franck Fajnkuchen, Sylvia Nghiem-Buffet, Typhaine Grenet, Gabriel Quentel, Corinne Delahaye-Mazza, Salomon Y. Cohen, and Audrey Giocanti-Aurégan

Subjects
Ophthalmology, RE1-994
Abstract

Purpose. To assess real-life efficacy of ranibizumab and treatment compliance of patients with vision loss secondary to diabetic macular edema (DME). Methods. A retrospective study was conducted in DME patients treated with ranibizumab. Patients were monitored every 4 weeks for visual acuity (VA) and central retinal thickness (CRT) by SD-OCT. All patients received a loading dose of 3 monthly injections followed by retreatments on an as-needed basis. The primary endpoint was the change in VA at M12. Patient compliance to the follow-up and the correlation between the injection number and VA were also investigated. Compliance was compared to that of neovascular age-related macular degeneration (nAMD) patients. Results. Seventy-two eyes of 55 consecutive DME patients were included. At baseline, the mean VA was 56.5 letters and CRT was 470 μm. At M12, the mean VA was 63.4 letters (p 70 letters, the mean VA change was +6.9 letters, and the mean CRT was 361.9 μm (p=0.0001) after a mean number of 5.33 intravitreal injections. In patients who received ≥7 injections, the VA gain and final VA were significantly higher than in patients who received

Published
2018
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17. Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Author

Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A. L., M. Diez A. R., A. Fernandez A. R., F. Fruhwald A. T., Fazlibegovic, E., P. Gatzov B. G., A. Kurlianskaya B. Y., R. Hullin C. H., T. Christodoulides C. Y., J. Hradec C. Z., O. Wendelboe Nielsen D. K., R. Nedjar D. Z., T. Uuetoa E. E., M. Hassanein E. G., J. F. Delgado Jimenez E. S., P. Harjola F. I., V, D. Logeart F. R., V. Chumburidze G. E., D. Tousoulis G. R., D. Milicic H. R., B. Merkely H. U., O'Donoghue IE, E., O. Amir I. L., A. Shotan I. L., D. Shafie I. R., M. Metra I. T., A. Matsumori J. P., E. Mirrakhimov K. G., A. Kavoliuniene L. T., A. Erglis L. V., Vataman, E., M. Otljanska M. K., E. Srbinovska Kostovska M. K., D. Cassar DeMarco M. T., J. Drozdz P. L., Fonseca, C., O. Chioncel R. O., M. Dekleva R. S., E. Shkolnik R. U., U. Dahlstrom S. E., M. Lainscak S. I., E. Goncalvesova S. K., A. Temizhan T. R., V. Estrago U. Y., G. Bajraktari X. K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A., L., M. Diez A., R., A. Fernandez A., R., F. Fruhwald A., T., Fazlibegovic, E., P. Gatzov B., G., A. Kurlianskaya B., Y., R. Hullin C., H., T. Christodoulides C., Y., J. Hradec C., Z., O. Wendelboe Nielsen D., K., R. Nedjar D., Z., T. Uuetoa E., E., M. Hassanein E., G., J. F. Delgado Jimenez E., S., V-, P. Harjola F. I., D. Logeart F., R., V. Chumburidze G., E., D. Tousoulis G., R., D. Milicic H., R., B. Merkely H., U., O'Donoghue IE, E., O. Amir I., L., A. Shotan I., L., D. Shafie I., R., M. Metra I., T., A. Matsumori J., P., E. Mirrakhimov K., G., A. Kavoliuniene L., T., A. Erglis L., V., Vataman, E., M. Otljanska M., K., E. Srbinovska Kostovska M., K., D. Cassar DeMarco M., T., J. Drozdz P., L., Fonseca, C., O. Chioncel R., O., M. Dekleva R., S., E. Shkolnik R., U., U. Dahlstrom S., E., M. Lainscak S., I., E. Goncalvesova S., K., A. Temizhan T., R., V. Estrago U., Y., G. Bajraktari X., K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., University of Zurich, and Seferović, Petar M

Subjects
Male, Registry, medicine.medical_specialty, Adverse outcomes, 610 Medicine & health, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Independent predictor, 2705 Cardiology and Cardiovascular Medicine, Ventricular Function, Left, 03 medical and health sciences, Age, 0302 clinical medicine, Internal medicine, Age related, Hospitalization, Mortality, Sex, medicine, Humans, Registries, Medical prescription, Aged, Heart Failure, Ejection fraction, business.industry, Stroke Volume, medicine.disease, Ageing, Heart failure, 10209 Clinic for Cardiology, Female, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, business
Abstract

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

Published
2019

20. Simple Scoring System to Predict In‐Hospital Mortality After Surgery for Infective Endocarditis

Author

Giuseppe Gatti, Andrea Perrotti, Jean‐François Obadia, Xavier Duval, Bernard Iung, François Alla, Catherine Chirouze, Christine Selton‐Suty, Bruno Hoen, Gianfranco Sinagra, François Delahaye, Pierre Tattevin, Vincent Le Moing, Aniello Pappalardo, and Sidney Chocron

Subjects
cardiac valvular surgery, critical care, infective endocarditis, mortality, predictors, pulmonary hypertension, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundAspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in‐hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. Methods and ResultsOutcomes of 361 consecutive patients (mean age, 59.1±15.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in‐hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty‐six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in‐hospital death. A scoring system was devised to predict in‐hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734–0.822). The score performed better than 5 of 6 scoring systems for in‐hospital death after cardiac surgery that were considered. ConclusionsA simple scoring system based on risk factors for in‐hospital death was specifically created to predict mortality risk postsurgery in patients with IE.

Published
2017
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23. Climate, soil resources and microbial activity shape the distributions of mountain plants based on their functional traits

Author

Jérôme Poulenard, Amélie Saillard, Julien Renaud, Wilfried Thuiller, Cédric Dentant, Tamara Münkemüller, Maxime Rome, Camille Martinez-Almoyna, Gabin Piton, Virgile Noble, Philippe Choler, Sylvain Abdulhak, Thierry Delahaye, Arnaud Foulquier, Louise Boulangeat, Environnements, Dynamiques et Territoires de la Montagne (EDYTEM), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire d'Ecologie Alpine (LECA ), and Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
[SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0106 biological sciences, 2. Zero hunger, Ecology, [SDE.MCG]Environmental Sciences/Global Changes, fungi, hierarchical species distribution model, plant biogeography, food and beverages, [SDV.BID]Life Sciences [q-bio]/Biodiversity, 15. Life on land, 010603 evolutionary biology, 01 natural sciences, ORCHAMP, Soil resources, 13. Climate action, [SDE]Environmental Sciences, trait-based model, Environmental science, extracellular enzymatic activity, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, French Alps, Ecology, Evolution, Behavior and Systematics, 010606 plant biology & botany
Abstract

International audience; While soil ecosystems undergo important modifications due to global change, the effect of soil properties on plant distributions is still poorly understood. Plant growth is not only controlled by soil physico-chemistry but also by microbial activities through the decomposition of organic matter and the recycling of nutrients essential for plants. A growing body of evidence also suggests that plant functional traits modulate spe-cies' response to environmental gradients. However, no study has yet contrasted the importance of soil physico-chemistry, microbial activities and climate on plant species distributions, while accounting for how plant functional traits can influence species-specific responses. Using hierarchical effects in a multi-species distribution model, we investigate how four functional traits related to resource acquisition (plant height, leaf carbon to nitrogen ratio, leaf dry matter content and specific leaf area) modulate the response of 44 plant species to climatic variables, soil physico-chemical properties and microbial decomposition activity (i.e. exoenzymatic activities) in the French Alps. Our hierarchical trait-based model allowed to predict well 41 species according to the TSS statistic. In addition to climate, the combination of soil C/N, as a measure of organic matter quality, and exoenzymatic activity, as a measure of microbial decomposition activity, strongly improved predictions of plant distributions. Plant traits played an important role. In particular, species with conservative traits performed better under limiting nutrient conditions but were outcompeted by exploitative plants in more favorable environments. We demonstrate tight associations between microbial decomposition activity, plant functional traits associated to different resource acquisition strategies and plant distributions. This highlights the importance of plant-soil linkages for mountain plant distributions. These results are crucial for biodiversity modelling in a world where both climatic and soil systems are undergoing profound and rapid transformations.

Published
2020

24. New evidence that biallelic loss of function in EEF1B2 gene leads to intellectual disability

Author

Lise Larcher, Julien Buratti, Brigitte Benzacken, Boris Keren, Bénédicte Héron‐Longe, Eva Pipiras, and Andrée Delahaye-Duriez

Subjects
Male, 0301 basic medicine, Protein subunit, Loss of Heterozygosity, 030105 genetics & heredity, Biology, Pathogenesis, Consanguinity, 03 medical and health sciences, Peptide Elongation Factor 1, Intellectual Disability, Intellectual disability, Genetics, medicine, Guanine Nucleotide Exchange Factors, Humans, Genetic Predisposition to Disease, Child, Gene, Genetics (clinical), Loss function, Siblings, Homozygote, EEF1B2, medicine.disease, Pedigree, 030104 developmental biology, Neurodevelopmental Disorders, Child, Preschool, Mutation, EEF1B2 Gene, Female, Guanine nucleotide exchange factor
Abstract

The guanine exchange factor subunit eEF1Bα encoded by the EEF1B2 gene belongs to the eukaryotic elongation translational machinery. Pathogen variants in genes of the translational machinery have been associated with several neurodevelopmental disorders. However, only one family of three siblings with intellectual disability (ID) has been reported so far with a homozygous variant in EEF1B2. Here, we report a second family with a novel homozygous loss of function (LoF) variant p.(Ser128*), carried by two siblings with moderate ID and seizures. Our findings confirm the role of EEF1B2 variants in the pathogenesis of autosomal-recessive ID, expand the variant spectrum and precisely describe the clinical consequences of the LoF of EEF1B2.

Published
2020

28. An open‐label, nonrandomized, phase Ib feasibility study of cusatuzumab in patients with nasopharyngeal carcinoma

Author

De Meulenaere, Astrid, primary, Vermassen, Tijl, additional, Creytens, David, additional, De Keukeleire, Stijn, additional, Delahaye, Tim, additional, Deron, Philippe, additional, Duprez, Fréderic, additional, Fung, Samson, additional, Pauwels, Patrick, additional, Ferdinande, Liesbeth, additional, and Rottey, Sylvie, additional

Published
2021
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33. Diagnostic lumbar puncture in people with Down syndrome: The experience of the Jerome Lejeune Institute

Author

Anne-Sophie Rebillat and Anne Hiance-Delahaye

Subjects
medicine.medical_specialty, Down syndrome, Epidemiology, business.industry, Health Policy, Diagnostic lumbar puncture, media_common.quotation_subject, medicine.disease, Method development, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, medicine, Quality (business), Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business, media_common
Published
2020

35. Prevalence of low health literacy levels in decompensated heart failure compared with acute myocardial infarction patients

Author

Perrin, Adèle, primary, Abdalla, Gergis, additional, Viprey, Marie, additional, Delahaye, François, additional, Mewton, Nathan, additional, Ovize, Michel, additional, Sebbag, Laurent, additional, Bochaton, Thomas, additional, Dima, Alexandra L., additional, Bravant, Estelle, additional, Schott, Anne‐Marie, additional, and Haesebaert, Julie, additional

Published
2021
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37. Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

Author

Delsart, Pascal, primary, Delahaye, Camille, additional, Devos, Patrick, additional, Domanski, Olivia, additional, Azzaoui, Richard, additional, Sobocinski, Jonathan, additional, Juthier, Francis, additional, Vincentelli, Andre, additional, Rousse, Natacha, additional, Mugnier, Agnes, additional, Soquet, Jerome, additional, Loobuyck, Valentin, additional, Koussa, Mohamed, additional, Modine, Thomas, additional, Jegou, Bruno, additional, Bical, Antoine, additional, Hysi, Ilir, additional, Fabre, Olivier, additional, Pontana, François, additional, Matran, Regis, additional, Mounier‐Vehier, Claire, additional, and Montaigne, David, additional

Published
2020
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43. Investigation of the sintering mechanisms of GDC pellets obtained by the compaction of nanostructured oxide microspheres

Author

Thibaud Delahaye, Rémy Boulesteix, Marie Caisso, Sébastien Picart, Alexandre Maitre, André Ayral, CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Axe 1 : procédés céramiques, Science des Procédés Céramiques et de Traitements de Surface (SPCTS), Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CEA PACFA program, and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, GDC compounds, Oxide, Pellets, Compaction, Sintering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, Microsphere, chemistry.chemical_compound, CRMP process, porous nanomaterials, Materials Chemistry, [CHIM]Chemical Sciences, Composite material, Porosity, sintering, 021001 nanoscience & nanotechnology, dilatometry, 0104 chemical sciences, chemistry, Ceramics and Composites, Crystallite, Particle size, 0210 nano-technology
Abstract

The sintering behavior of green pellets obtained from nanostructured Ce0.8Gd0.2O1.9 submillimetric microspheres is studied in the present paper. Corresponding shrinkage rate curve shows a two-step densification in dynamic conditions, with the presence of two successive extrema, at 1200 K and 1500 K. To fully understand this non-common densification behavior, an iterative study was performed. Multiple characterizations point out multiscale organization of the matter with temperature giving rise to differential sintering stages of two different particle size classes. Concerning 1200 K-first shrinkage rate maximum, it corresponds to the densification of nanometric aggregates of crystallites into submicrometric pre-sintered aggregates, resulting in a specific porous microstructure with residual open porosity. As-generated porosity combined with submicron size of pre-sintered aggregates thus prevent from a homogeneous sintering illustrated by a single maximum shrinkage rate. Finally, the second maximum shrinkage rate at 1500 K can then be associated to optimal temperature for submicrometric particles sintering. This article is protected by copyright. All rights reserved.

Published
2017

44. Error Budget of the MEthane Remote LIdar missioN and Its Impact on the Uncertainties of the Global Methane Budget

Author

Bruno Millet, Achim Friker, Patrick Rairoux, Christoph Kiemle, Cyril Crevoisier, Andreas Fix, Vincent Cassé, Mathias Alpers, Frederic Esteve, Martin Wirth, Frédéric Chevallier, Fabien Gibert, Gerhard Ehret, Clémence Pierangelo, Julia Marshall, Cédric Bacour, Jordi Chinaud, Caroline Bes, Thibault Delahaye, François-Marie Bréon, A. Klonecki, R. Armante, Pradeebane Vaittinada Ayar, Olivier Chomette, Dimitri Edouart, Philippe Bousquet, Philippe Peylin, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Modélisation INVerse pour les mesures atmosphériques et SATellitaires (SATINV), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National d'Études Spatiales [Toulouse] (CNES), NOVELTIS [Sté], Max-Planck-Institut für Biogeochemie (MPI-BGC), Modélisation des Surfaces et Interfaces Continentales (MOSAIC), DLR Institut für Physik der Atmosphäre (IPA), Deutsches Zentrum für Luft- und Raumfahrt [Oberpfaffenhofen-Wessling] (DLR), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Deutsches Zentrum für Luft- und Raumfahrt [Bonn] (DLR), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Atmospheric Science, 010504 meteorology & atmospheric sciences, Meteorology, methane emissions, 010502 geochemistry & geophysics, 01 natural sciences, atmospheric methane, global methane budget, Methane, Latitude, chemistry.chemical_compound, inversion, Earth and Planetary Sciences (miscellaneous), Uncertainty reduction theory, 0105 earth and related environmental sciences, [PHYS.PHYS.PHYS-AO-PH]Physics [physics]/Physics [physics]/Atmospheric and Oceanic Physics [physics.ao-ph], Lidar, Atmospheric methane, Inversion (meteorology), Ranging, uncertainties, error budget, Impact study, MERLIN, Geophysics, chemistry, 13. Climate action, Space and Planetary Science, Greenhouse gas, Environmental science, Raumfahrtmanagement, space-based Lidar, MERLIN mission
Abstract

International audience; MEthane Remote LIdar missioN (MERLIN) is a German‐French space mission, scheduled for launch in 2024 and built around an innovative light detecting and ranging instrument that will retrieve methane atmospheric weighted columns. MERLIN products will be assimilated into chemistry transport models to infer methane emissions and sinks. Here the expected performance of MERLIN to reduce uncertainties on methane emissions is estimated. A first complete error budget of the mission is proposed based on an analysis of the plausible causes of random and systematic errors. Systematic errors are spatially and temporally distributed on geophysical variables and then aggregated into an ensemble of 32 scenarios. Observing System Simulation Experiments are conducted, originally carrying both random and systematic errors. Although relatively small (±2.9 ppb), systematic errors are found to have a larger influence on MERLIN performances than random errors. The expected global mean uncertainty reduction on methane emissions compared to the prior knowledge is found to be 32%, limited by the impact of systematic errors. The uncertainty reduction over land reaches 60% when the largest desert regions are removed. At the latitudinal scale, the largest uncertainty reductions are achieved for temperate regions (84%) and then tropics (56%) and high latitudes (53%). Similar Observing System Simulation Experiments based on error scenarios for Greenhouse Gases Observing SATellite reveal that MERLIN should perform better than Greenhouse Gases Observing SATellite for most continental regions. The integration of error scenarios for MERLIN in another inversion system suggests similar results, albeit more optimistic in terms of uncertainty reduction.

Published
2018

45. Gene expression of MAGE-A3 and PRAME tumor antigens and EGFR mutational status in Taiwanese non-small cell lung cancer patients

Author

An de Creus, Nicolas F. Delahaye, Bart Spiessens, Aung Myo, Sung-Liang Yu, Jamila Louahed, Nicole Kusuma, Olivier Gruselle, Szu-Hua Pan, Gee-Cheng Chang, Kang-Yi Su, and Pan-Chyr Yang

Subjects
Adult, Male, 0301 basic medicine, Oncology, MAGEA3, medicine.medical_specialty, Lung Neoplasms, Population, Taiwan, Single-nucleotide polymorphism, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Internal medicine, Biomarkers, Tumor, Humans, Medicine, education, Lung cancer, Aged, Retrospective Studies, PRAME, education.field_of_study, Polymorphism, Genetic, business.industry, Melanoma, General Medicine, Middle Aged, medicine.disease, digestive system diseases, Neoplasm Proteins, Reverse transcription polymerase chain reaction, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Adenocarcinoma, Female, business
Abstract

Aim To determine the frequency of expression of the tumor-associated antigens (TAAs) melanoma-associated antigen A3 (MAGE-A3) and preferentially expressed antigen of melanoma (PRAME) and the rate of EGFR mutations in a Taiwanese non–small cell lung cancer (NSCLC) population including only adenocarcinomas and squamous cell carcinomas. Furthermore, to investigate associations between TAA expression and EGFR mutations and to evaluate these TAAs as prognostic markers for overall survival. The occurrence of single nucleotide polymorphisms in MAGEA3 and PRAME was also assessed. Methods Archival fresh-frozen tumor tissue specimens were tested by quantitative reverse transcription polymerase chain reaction assays to detect MAGE-A3 and PRAME expression. EGFR mutations were detected by mass spectroscopy and single nucleotide polymorphisms by gene sequencing. Results Of the 156 adenocarcinomas examined, 3.3% expressed MAGE-A3, 32.2% expressed PRAME and 62.8% had EGFR mutations. Of the 128 squamous cell carcinomas, 29.8% expressed MAGE-A3, 59.2% expressed PRAME and 20.5% harbored EGFR mutations. TAA expression was similar across subgroups determined by patient or tumor characteristics. There was no association between TAA expression and EGFR mutation status and TAA expression was found not to be a prognostic marker for survival. Single nucleotide polymorphisms were identified, one of which with a possible impact on MAGE-A3 expression. Conclusions In this NSCLC population, expression of MAGE-A3 and PRAME was more frequent in squamous cell carcinomas than in adenocarcinomas tumors. EGFR mutations were not associated with TAA expression for either histology and were three times more frequent in adenocarcinomas than in squamous cell carcinomas tumors.

Published
2016

46. Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition

Author

Jessica Tozour, Hye Heo, Lingguang Cui, Fabien Delahaye, Francine H. Einstein, Yongmei Zhao, and Nir Barzilai

Subjects
Male, 0301 basic medicine, Aging, medicine.medical_specialty, Offspring, Biology, liver, maternal overnutrition, Epigenesis, Genetic, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Overnutrition, Pregnancy, Internal medicine, medicine, Animals, Epigenetics, Genetic Association Studies, 2. Zero hunger, DNA methylation, Genome, Malnutrition, maternal undernutrition, Original Articles, Cell Biology, Methylation, medicine.disease, Phenotype, Disease Models, Animal, 030104 developmental biology, Endocrinology, In utero, 030220 oncology & carcinogenesis, Lipogenesis, Original Article, Female
Abstract

Summary Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers’ nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease.

Published
2016

47. A series of 38 novel germline and somatic mutations ofNIPBLin Cornelia de Lange syndrome

Author

Hervé Testard, Martine Doco-Fenzy, Alice Goldenberg, Fabienne Prieur, Caroline Michot, Marcia Henry, Sandrine Marlin, Sophie Blesson, Clarisse Baumann, Valérie Cormier-Daire, Philippe Loget, Sylvie Odent, Marlène Rio, Anne-Lise Delezoide, Andrée Delahaye-Duriez, Jean-Paul Bonnefont, Anne Dieux-Coeslier, Audrey Putoux, Marie-Pierre Cordier-Alex, Ghislaine Plessis, Valérie Layet, Albert David, Mathilde Nizon, Bettina Bessières, Jelena Martinovic, Laurent Pasquier, Anne Bazin, and Laurence Faivre

Subjects
0301 basic medicine, Genetics, Sanger sequencing, Mutation, Microcephaly, Cornelia de Lange Syndrome, Genetic counseling, Buccal swab, NIPBL, Biology, medicine.disease_cause, medicine.disease, Germline, 3. Good health, 03 medical and health sciences, symbols.namesake, 030104 developmental biology, medicine, symbols, Genetics (clinical)
Abstract

Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to an heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: 1) intrauterine growth retardation and postnatal short stature, 2) feeding difficulties and/or gastro-oesophageal reflux, 3) microcephaly, 4) intellectual disability and 5) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and three in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for twenty cases which does not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counseling

Published
2016

48. Temporal evolution of collar lesions associated with ash dieback and the occurrence ofArmillariain Belgian forests

Author

M. Herman, G. San Martin, L. Delahaye, F. Gerarts, and Anne Chandelier

Subjects
0106 biological sciences, 0301 basic medicine, Ecology, Armillaria, biology, Hymenoscyphus fraxineus, Crown (botany), Forestry, Context (language use), 030108 mycology & parasitology, biology.organism_classification, Fraxinus, Positive correlation, 01 natural sciences, Collar, 03 medical and health sciences, medicine.drug_formulation_ingredient, Horticulture, Botany, medicine, 010606 plant biology & botany
Abstract

Summary Ash dieback, caused by the fungus Hymenoscyphus fraxineus, has been observed in Europe for several years. In Belgium, the disease was first reported in 2010. Besides crown defoliation and dieback, collar lesions have sometimes been reported. To evaluate the prevalence and the progression of collar lesions and crown defoliation in ash dieback-affected stands of various ages, a survey was conducted in 2013 and 2014 on 268 ash trees (Fraxinus excelsior) originating from 17 Walloon forest stands. The results showed that the proportion of trees with collar lesions greatly increased between June 2013 and September 2014 and that there appeared to be no significant link between a tree's diameter-at-breast height (DBH) and collar lesion occurrence. The mean percentage of defoliation increased in each forest stand across time, with observations conducted in September 2013 and 2014 showing a positive correlation with the mean percentage of trees with collar lesions. Molecular tests were carried out on 103 additional trees originating from 12 of the 17 stands to evaluate the occurrence of H. fraxineus and Armillaria spp. at the collar level. Most of the trees (98%) were infected by H. fraxineus. In contrast, only 41% of the samples were infected with Armillaria spp., most commonly A. gallica and A. cepistipes. This study discusses the role of Armillaria spp. and the rapid increase in the number of trees with collar lesions within the context of the evolution of ash dieback in Europe.

Published
2016

49. Integrated systems‐genetic analyses reveal a network target for delaying glioma progression

Author

Laaniste, Liisi, primary, Srivastava, Prashant K., additional, Stylianou, Julianna, additional, Syed, Nelofer, additional, Cases‐Cunillera, Silvia, additional, Shkura, Kirill, additional, Zeng, Qingyu, additional, Rackham, Owen J. L., additional, Langley, Sarah R., additional, Delahaye-Duriez, Andree, additional, O'Neill, Kevin, additional, Williams, Matthew, additional, Becker, Albert, additional, Roncaroli, Federico, additional, Petretto, Enrico, additional, and Johnson, Michael R., additional

Published
2019
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