Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) Cells

BACKGROUND: mTOR kinase forms the mTORC1 complex by associating with raptor and other proteins and affects a number of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E-BP1, with the latter negatively regulating eukaryotic initiation factor 4E (eIF-4E). MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E. Rapamycin and its analogs are highly specific, potent, and relatively non-toxic inhibitors of mTORC1. Although mTORC1 activation is present in many types of malignancies, rapamycin-type inhibitors shows relatively limited clinical efficacy as single agents. Initially usually indolent, CTCL displays a tendency to progress to the aggressive forms with limited response to therapy and poor prognosis. Our previous study (M. Marzec et al. 2008) has demonstrated that CTCL cells display mTORC1 activation and short-term treatment of CTCL-derived cells with rapamycin suppressed their proliferation and had little effect on the cell survival. METHODS: Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and MNK inhibitor and evaluated for inhibition of the mTORC1 signaling pathway and cell growth and survival. RESULTS: Whereas the treatment with rapamycin persistently inhibited mTORC1 signaling, it suppressed only partially the cell growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferation of the CTCL cells when combined with the rapamycin-mediated inhibition of mTORC1. While MNK inhibition alone mildly suppressed the CTCL cell growth, the combined MNK and mTORC1 inhibition totally abrogated the growth. Similarly, MNK inhibitor alone displayed a minimal pro-apoptotic effect; in combination with rapamycin it triggered profound cell apoptosis. CONCLUSIONS: These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of CTCL and other malignancies

An automated, cost-effective and scalable, flood-and-drain based root phenotyping system for cereals

Background: Genetic studies on the molecular mechanisms of the regulation of root growth require the characterisation of a specific root phenotype to be linked with a certain genotype. Such studies using classical labour-intensive methods are severely hindered due to the technical limitations that are associated with the impeded observation of the root system of a plant during its growth. The aim of the research presented here was to develop a reliable, cost-effective method for the analysis of a plant root phenotype that would enable the precise characterisation of the root system architecture of cereals. Results: The presented method describes a complete system for automatic supplementation and continuous sensing of culture solution supplied to plants that are grown in transparent tubes containing a solid substrate. The presented system comprises the comprehensive pipeline consisting of a modular-based and remotely-controlled plant growth system and customized imaging setup for root and shoot phenotyping. The system enables an easy extension of the experimental capacity in order to form a combined platform that is comprised of parallel modules, each holding up to 48 plants. The conducted experiments focused on the selection of the most suitable conditions for phenotyping studies in barley: an optimal size of the glass beads, diameters of the acrylic tubes, composition of a medium, and a rate of the medium flow. Conclusions: The developed system enables an efficient, accurate and highly repeatable analysis of the morphological features of the root system of cereals. Because a simple and fully-automated control system is used, the experimental conditions can easily be normalised for different species of cereals. The scalability of the module-based system allows its capacity to be adjusted in order to meet the requirements of a particular experiment

Defective Proinsulin Handling Modulates the MHC I Bound Peptidome and Activates the Inflammasome in β-Cells

How immune tolerance is lost to pancreatic β-cell peptides triggering autoimmune type 1 diabetes is enigmatic. We have shown that loss of the proinsulin chaperone glucose-regulated protein (GRP) 94 from the endoplasmic reticulum (ER) leads to mishandling of proinsulin, ER stress, and activation of the immunoproteasome. We hypothesize that inadequate ER proinsulin folding capacity relative to biosynthetic need may lead to an altered β-cell major histocompatibility complex (MHC) class-I bound peptidome and inflammasome activation, sensitizing β-cells to immune at-tack. We used INS-1E cells with or without GRP94 knockout (KO), or in the presence or absence of GRP94 inhibitor PU-WS13 (GRP94i, 20 µM), or exposed to proinflammatory cytokines interleukin (IL)-1β or interferon gamma (IFNγ) (15 pg/mL and 10 ng/mL, respectively) for 24 h. RT1.A (rat MHC I) expression was evaluated using flow cytometry. The total RT1.A-bound peptidome analysis was performed on cell lysates fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC), followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein (NLRP1), nuclear factor of kappa light polypeptide gene enhancer in B-cells in-hibitor alpha (IκBα), and (pro) IL-1β expression and secretion were investigated by Western blot-ting. GRP94 KO increased RT1.A expression in β-cells, as did cytokine exposure compared to relevant controls. Immunopeptidome analysis showed increased RT1.A-bound peptide repertoire in GRP94 KO/i cells as well as in the cells exposed to cytokines. The GRP94 KO/cytokine exposure groups showed partial overlap in their peptide repertoire. Notably, proinsulin-derived peptide diversity increased among the total RT1.A peptidome in GRP94 KO/i along with cytokines exposure. NLRP1 expression was upregulated in GRP94 deficient cells along with decreased IκBα content while proIL-1β cellular levels declined, coupled with increased secretion of mature IL-1β. Our results suggest that limiting β-cell proinsulin chaperoning enhances RT1.A expression alters the MHC-I peptidome including proinsulin peptides and activates inflammatory pathways, suggesting that stress associated with impeding proinsulin handling may sensitize β-cells to immune-attack

Correction to: Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry (Infection, (2022), 50, 5, (1191-1202), 10.1007/s15010-022-01792-0)

In this article the “EURO-ENDO Investigators group” member U. Y. Sinan was incorrectly written as U.S. Yasar. The original article has been corrected

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

none912Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.nonePazdernik, Michal; Iung, Bernard; Mutlu, Bulent; Alla, François; Riezebos, Robert; Kong, William; Nunes, Maria Carmo Pereira; Pierard, Luc; Srdanovic, Ilija; Yamada, Hirotsugu; De Martino, Andrea; Miglioranza, Marcelo Haertel; Magne, Julien; Piper, Cornelia; Laroche, Cécile; Maggioni, Aldo P; Lancellotti, Patrizio; Habib, Gilbert; Selton-Suty, Christine, EURO-ENDO Investigators group: R Ronderos, G Avegliano, P Fernandez Oses, E Filipini, I Granada, A Iribarren, M Mahia, F Nacinovich, S Ressi, R Obregon, M Bangher, J Dho, L Cartasegna, M L Plastino, V Novas, C Shigel, G Reyes, M De Santos, N Gastaldello, M Granillo Fernandez, M Potito, G Streitenberger, P Velazco, J H Casabé, C Cortes, E Guevara, F Salmo, M Seijo, F Weidinger, M Heger, R Brooks, C Stöllberger, C-Y Ho, L Perschy, L Puskas, G Goliasch, C Binder, R Rosenhek, M Schneider, M-P Winter, E Hoffer, M Melissopoulou, E Lecoq, D Legrand, S Jacquet, M Massoz, P Lancellotti, L Pierard, R Dulgheru, S Marchetta, C D Emal, C Oury, B Cosyns, S Droogmans, D Kerkhove, A Motoc, D Plein, B Roosens, L Soens, C Weytjens, I Lemoine, I Rodrigus, B Paelinck, B Amsel, P Unger, D Konopnicki, C Beauloye, A Pasquet, S Pierard, D Vancraeynest, J L Vanoverschelde, F Sinnaeve, J L Andrade, A C Tude Rodrigues, K Staszko, R Dos Santos Monteiro, M H Miglioranza, D L Shuha, M Alcantara, V Cravo, L Fazzio, A Felix, M Iso, C Musa, A P Siciliano, F Villaca Filho, J Braga, A Rodrigues, R Silva, F Vilela, D Rodrigues, L Silva, S Morhy, C Fischer, R Silva, M Vieira, T Afonso, J Abreu, S N Falcao, V Moises, A Gouvea, G João, F Mancuso, C Silva, A C Souza, C S Abboud, R Bellio de Mattos Barretto, A Ramos, R Arnoni, J E Assef, D J Della Togna, D Le Bihan, L Miglioli, A P Romero Oliveira, R Tadeu Magro Kroll, D Cortez, C L Gelape, M D C Peirira Nunes, T C De Abreu Ferrari, K-L Chan, K Hay, V Le, M Page, F Poulin, C Sauve, K Serri, C Mercure, J Beaudoin, P Pibarot, I Sebag, L Rudski, G Ricafort, B Barsic, V Krajinovic, M Vargovic, J Separovic-Hanzevacki, D Lovric, V Reskovic-Luksic, J Vincelj, S Jaksic Jurinjak, V Yiannikourides, M Ioannides, C Kyriakou, C Pofaides, V Masoura, K Yiangou, J Pudich, A Linhart, M Siranec, J Marek, K Blechova, M Kamenik, M Pazdernik, R Pelouch, Z Coufal, M Mikulica, M Griva, E Jancova, M Mikulcova, M Taborsky, J Precek, M Jecmenova, J Latal, J Widimsky, T Butta, S Machacek, R Vancata, J Spinar, M Holicka, F Pow Chon Long, N Anzules, A Bajana Carpio, G Largacha, E Penaherrera, D Moreira, E Mahfouz, E Elsafty, A Soliman, Y Zayed, J Aboulenein, M Abdel-Hay, A Almaghraby, M Abdelnaby, M Ahmed, B Hammad, Y Saleh, H Zahran, O Elgebaly, A Saad, M Ali, A Zeid, R El Sharkawy, M Meshaal, A Al Kholy, R Doss, D Osama, H Rizk, A Elmogy, M Mishriky, P Assayag, S El Hatimi, Saint- E Botelho-Nevers, S Campisi, J-F Fuzellier, A Gagneux-Brunon, R Pierrard, C Tulane, M Detoc, T Mehalla, D Boutoille, O Al Habash, N Asseray-Madani, C Biron, J Brochard, J Caillon, C Cueff, T Le Tourneau, A S Lecompte, R Lecomte, M Lefebvre, M M Magali Michel, S Pattier, S Delarue, M Le Bras, J Orain, J-F Faucher, V Aboyans, A Beeharry, H Durox, M Lacoste, J Magne, D Mohty, A David, V Pradel, V Sierra, A Neykova, B Bettayeb, S Elkentaoui, B Tzvetkov, G Landry, C Strady, K Ainine, S Baumard, C Brasselet, C Tassigny, V Valente-Pires, M Lefranc, B Hoen, B Lefevre, E Curlier, C Callier, N Fourcade, Y Jobic, S Ansard, R Le Berre, P Le Roux, F Le Ven, M-C Pouliquen, G Prat, F Bouchart, A Savoure, C Alarcon, C Chapuzet, I Gueit, C Tribouilloy, Y Bohbot, F Peugnet, M Gun, B Iung, X Duval, X Lescure, E Ilic-Habensus, N Sadoul, C Selton-Suty, F Alla, E Chevalier, F Goehringer, O Huttin, R Garcia, V Le Marcis, P Tattevin, E Donal, E Flecher, M Revest, G Habib, S Hubert, J-P Casalta, F Gouriet, F Arregle, S Cammilleri, L Tessonnier, A Riberi, C Chirouze, K Bouiller, A-S Brunel, D Fournier, L Hustache-Mathieu, T Klopfenstein, J Moreau, P Lim, L Oliver, J Ternacle, A Moussafeur, P Chavanet, L Piroth, M Buisson, S Mahy, C Martins, A Salmon-Rousseau, S Gohier, C Piper, J Börgermann, D Guckel, D Horstkotte, B Brockmeier, E Winkelmann, A Hagendorff, D Grey, G Nickenig, R Schueler, C Öztürk, E Stöhr, C Hamm, T Walther, R Brandt, A-C Frühauf, C T Hartung, C Hellner, C Wild, M Becker, S Hamada, W Kaestner, K Stangl, F Knebel, G Baldenhofer, A Brecht, H Dreger, C Isner, F Pfafflin, M Stegemann, R Zahn, B Fraiture, C Kilkowski, A-K Karcher, S Klinger, H Tolksdorf, D Tousoulis, C Aggeli, G Sarri, S Sideris, E Venieri, G Athanassopoulos, D Tsiapras, I Armenis, A Koutsiari, G Floros, C Grassos, S Dragasis, L Rallidis, C Varlamos, L Michalis, K Naka, A Bechlioulis, A Kotsia, L Lakkas, K Pappas, C Papadopoulos, S Kiokas, A Lioni, S Misailidou, J Barbetseas, M Bonou, C Kapelios, I Tomprou, K Zerva, A Manolis, E Hamodraka, D Athanasiou, G Haralambidis, L Poulimenos, H Samaras, A Nagy, A Bartykowszki, E Gara, S Sengupta, K Mungulmare, R Kasliwal, M Bansal, A Bhan, S Ranjan, M Kyavar, M Maleki, F Noohi Bezanjani, A Sadeghpour, A Alizadehasl, S Boudagh, A Ghavidel, P Moradnejad, H R Pasha, B Ghadrdoost, D Gilon, J Strahilevitz, S Israel, M Wanounou, C d'Agostino, P Colonna, L De Michele, F Fumarola, M Stante, N Marchionni, V Scheggi, B Alterini, S Del Pace, P Stefano, C Sparano, L P Badano, D Muraru, N Ruozi, R Tenaglia, U Limbruno, A Cresti, P Baratta, M Solari, C Giannattasio, A Moreo, B De Chiara, B Lopez Montero, F Musca, C A Orcese, F Panzeri, C F Russo, F Spano, O Alfieri, M De Bonis, E Agricola, E Busnardo, S Carletti, B Castiglioni, S Chiappetta, B Del Forno, D Ferrara, M Guffanti, G Iaci, E Lapenna, T Nisi, C Oltolini, U Pajoro, R Pasciuta, M Ripa, P Scarpellini, C Tassan Din, R Meneghin, D Schiavi, F Piscione, R Citro, R M Benvenga, L Greco, C Prota, I Radano, L Soriente, M Bellino, D Di Vece, F Santini, A Salsano, G M Olivieri, F Turrini, R Messora, S Tondi, A Olaru, V Agnoletto, L Grassi, C Leonardi, S Sansoni, S Del Ponte, G M Actis Dato, A De Martino, N Ohte, S Kikuchi, K Wakami, K Aonuma, Y Seo, T Ishizu, T Machino-Ohtsuka, M Yamamoto, N Iida, H Nakajima, Y Nakagawa, C Izumi, M Amano, M Miyake, K Takahashi, I Shiojima, Y Miyasaka, H Maeba, Y Suwa, N Taniguchi, S Tsujimoto, T Kitai, M Ota, S Yuda, S Sasaki, N Hagiwara, K Yamazaki, K Ashihara, K Arai, C Saitou, S Saitou, G Suzuki, Y Shibata, N Watanabe, S Nishino, K Ashikaga, N Kuriyama, K Mahara, K Abe, H Fujimaki, T Okubo, H Shitan, S Takanashi, M Terada, H Yamamoto, M Sata, H Yamada, K Kusunose, Y Saijo, H Seno, O Yuichiro, Y Sakata, H Mizuno, S Nakatani, T Onishi, K Sengoku, F Sera, S W Park, K Eun Kyoung, L Ga Yeon, J-W Hwang, C Jin-Oh, S-J Park, L Sang-Chol, C Sung-A, S Y Jang, D-H Kang, R Heo, S Lee, J-M Song, E Jung, J Plisiene, A Dambrauskaite, G Gruodyte, R Jonkaitiene, J Vaskelyte, V Mizariene, J Atkocaityte, R Zvirblyte, R Sow, A Codreanu, E C L De la Vega, C Michaux, T Staub, L Jacobs-Orazi, C Mallia Azzopardi, R G Xuereb, T Piscopo, D Borg, R Casha, J Farrugia, M Fenech, E Pllaha, C Vella, K Yamagata, L Grib, E Raevschi, A Grejdieru, G Balan, I Cardaniuc, L Cardaniuc, V Corcea, A Feodorovici, V Gaina, L Girbu, P Jimbei, D Kravcenco, E Panfile, E Prisacari, E Samohvalov, S Samohvalov, N Sceglova, I Benesco, V Marian, N Sumarga, M Mirocevic, B Bozovic, N Bulatovic, P Lakovic, L Music, J Roos-Hesselink, R Budde, T Gamela, A Wahadat, O Kamp, T Meijers, J P Van Melle, V M Deursen, H Crijns, S Bekkers, E Cheriex, M Gilbers, B Kietselaer, C Knackstedt, R Lorusso, S Schalla, S Streukens, S Chamuleau, M-J Cramer, A Teske, T Van der Spoel, A Wind, O Liesbek, J Lokhorst, H Van Heusden, W Tanis, I Van der Bilt, J Vriend, H De Lange-van Bruggen, E Karijodikoro, R Riezebos, E van Dongen, J Schoep, V Stolk, O Axler, F Baumann, S Lebras, T Edvardsen, J T Offstad, J O Beitnes, T Helle-Valle, H Skulstad, R Skardal, N Qamar, S Furnaz, B Ahmed, M H Butt, M F Khanzada, T Saghir, A Wahid, T Hryniewiecki, P Szymanski, K Marzec, M Misztal-Ogonowska, W Kosmala, M Przewlocka-Kosmala, A Rojek, K Woznicka, J Zachwyc, A Lisowska, M Kaminska, J Kasprzak, E Kowalczyk, D F Strzecka, P Wejner-Mik, M Trabulo, P Freitas, S Ranchordas, G Rodrigues, P Pinto, C Queiros, J Azevedo, L Marques, D Seabra, L Branco, J Abreu, M Cruz, A Galrinho, R Moreira, P Rio, A T Timoteo, M Selas, N M Cardim, V Carmelo, B Duque Neves, H Pereira, I Cruz, A Guerra, A Marques, I Pintassilgo, M C Tomescu, N-M Trofenciuc, M Andor, A Bordejevic, H S Branea, F Caruntu, L Cirin, I M Citu, C A Cotoraci, D Darabantiu, R Farcas, I Marincu, A Mavrea, M F Onel, T Parvanescu, D Pop, A L Pop-Moldovan, M I Puticiu, L A Velcean, A Ionac, D Cozma, C Mornos, F Goanta, I Popescu, R Beyer, R Mada, R Rancea, H Rosianu, R Tomoaia, C Stanescu, Z Kobalava, J Karaulova, E Kotova, A Milto, A Pisaryuk, N Povalyaev, M Sorokina, J Alrahimi, A Elshiekh, A Jamiel, A Ahmed, M Al-Mallah, N Attia, B Putnikovic, A Neskovic, A Dimic, B Ivanovic, S Matic, D Trifunovic, J Petrovic, D Kosevic, P Dabic, P Milojevic, I Petrovic, I Stojanovic, I Srdanovic, M Kovacevic, A Redzek, M Stefanovic, S Susak, L Velicki, A Vulin, T C Yeo, W K F Kong, K K Poh, I Vilacosta, M Abd El- Nasser, C Ferrera, C Olmos, F Calvo Iglesias, E Blanco-Gonzalez, M Bravo Amaro, A N Germinas, E Lopez-Rodriguez, J Lugo Adan, P Pazos-Lopez, M Pereira Loureiro, M T Perez, S Raposeiras-Roubin, S Rasheed Yas, M-M Suarez-Varela, F Vasallo Vidal, D Garcia-Dorado, A Sambola, N Fernandez-Hidalgo, T Gonzalez-Alujas, J Lozano, O Maisterra, N Pizzi, R Rios, P Tornos, A Bayes-Genis, L Pedro Botet, N Vallejo, E Berastegui, C Llibre, L Mateu, R Nunez, D Quesada, D Bosch Portell, J Aboal Vinas, X Albert Bertran, R Brugada Tarradellas, P Loma-Osorio Ricon, C Tiron de Llano, M A Arnau, A Bel, M Blanes, A Osa, M Anguita, F Carrasco, J Castillo, J L Zamorano, J L Moya Mur, M Alvaro, C Fernandez-Golfin, J M Monteagudo, E Navas Elorza, M C Farinas Alvarez, J Aguero Balbin, C Arminanzas, F Arnaiz de Las Revillas, A Arnaiz Garcia, M Cobo Belaustegui, M Fernandez Sampedro, M Gutierrez Cuadra, J F Gutierrez-Diez, J Zarauza, L Garcia Cuello, C Gonzalez Rico, R Rodriguez-Alvarez, J Goikoetxea, M Montejo, J Miro, M Almela, J Ambrosioni, C Falces, D Fuster, C Garcia-de-la-Maria, M Hernandez-Meneses, J Llopis, F Marco, A Moreno, E Quintana, E Sandoval, A Tellez, J M Tolosana, B Vidal, I Ruiz-Zamora, A Bardaji Ruiz, E Sanz Girgas, G Garcia-Pardo, M Guillen Marzo, A Rodriguez Oviedo, A Villares Jimenez, L Abid, R Hammami, S Kammoun, M S Mourali, F Mghaieth Zghal, M Ben Hlima, S Boudiche, S Ouali, L Zakhama, S Antit, I Slama, O Gulel, M Sahin, L E Sade, E Karacaglar, S Kucukoglu, O Cetinarslan, U S Yasar, U Canpolat, B Mutlu, H Atas, R Dervishova, C Ileri, H Zaky, J Alhashmi, F Baslib, J Tahir, P Zarger, S Woldman, L Menezes, C Primus, R Uppal, I Bvekerwa, B Chandrasekaran, A Kopanska, B Prendergast, S Cannata, J Chambers, J Hancock, J Klein, R Rajani, M P Ursi, R Dworakowski, A Fife, J Breeze, M Browne-Morgan, M Gunning, S Streather, F Asch, M Zemedkun, B Alyavi, J UzokovMichal, Pazdernik; Bernard, Iung; Bulent, Mutlu; François, Alla; Robert, Riezebos; William, Kong; Maria Carmo Pereira, Nunes; Luc, Pierard; Ilija, Srdanovic; Hirotsugu, Yamada; Andrea, De Martino; Marcelo Haertel, Miglioranza; Julien, Magne; Cornelia, Piper; Cécile, Laroche; Aldo P, Maggioni; Patrizio, Lancellotti; Gilbert, Habib; Christine, Selton-Suty; R Ronderos, EURO-ENDO Investigators group:; Avegliano, G; Fernandez Oses, P; Filipini, E; Granada, I; Iribarren, A; Mahia, M; Nacinovich, F; Ressi, S; Obregon, R; Bangher, M; Dho, J; Cartasegna, L; L Plastino, M; Novas, V; Shigel, C; Reyes, G; De Santos, M; Gastaldello, N; Granillo Fernandez, M; Potito, M; Streitenberger, G; Velazco, P; H Casabé, J; Cortes, C; Guevara, E; Salmo, F; Seijo, M; Weidinger, F; Heger, M; Brooks, R; Stöllberger, C; Ho, C-Y; Perschy, L; Puskas, L; Goliasch, G; Binder, C; Rosenhek, R; Schneider, M; Winter, M-P; Hoffer, E; Melissopoulou, M; Lecoq, E; Legrand, D; Jacquet, S; Massoz, M; Lancellotti, P; Pierard, L; Dulgheru, R; Marchetta, S; D Emal, C; Oury, C; Cosyns, B; Droogmans, S; Kerkhove, D; Motoc, A; Plein, D; Roosens, B; Soens, L; Weytjens, C; Lemoine, I; Rodrigus, I; Paelinck, B; Amsel, B; Unger, P; Konopnicki, D; Beauloye, C; Pasquet, A; Pierard, S; Vancraeynest, D; L Vanoverschelde, J; Sinnaeve, F; L Andrade, J; C Tude Rodrigues, A; Staszko, K; Dos Santos Monteiro, R; H Miglioranza, M; L Shuha, D; Alcantara, M; Cravo, V; Fazzio, L; Felix, A; Iso, M; Musa, C; P Siciliano, A; Villaca Filho, F; Braga, J; Rodrigues, A; Silva, R; Vilela, F; Rodrigues, D; Silva, L; Morhy, S; Fischer, C; Silva, R; Vieira, M; Afonso, T; Abreu, J; N Falcao, S; Moises, V; Gouvea, A; João, G; Mancuso, F; Silva, C; C Souza, A; S Abboud, C; Bellio de Mattos Barretto, R; Ramos, A; Arnoni, R; E Assef, J; J Della Togna, D; Le Bihan, D; Miglioli, L; P Romero Oliveira, A; Tadeu Magro Kroll, R; Cortez, D; L Gelape, C; C Peirira Nunes, M D; C De Abreu Ferrari, T; Chan, K-L; Hay, K; Le, V; Page, M; Poulin, F; Sauve, C; Serri, K; Mercure, C; Beaudoin, J; Pibarot, P; Sebag, I; Rudski, L; Ricafort, G; Barsic, B; Krajinovic, V; Vargovic, M; Separovic-Hanzevacki, J; Lovric, D; Reskovic-Luksic, V; Vincelj, J; Jaksic Jurinjak, S; Yiannikourides, V; Ioannides, M; Kyriakou, C; Pofaides, C; Masoura, V; Yiangou, K; Pudich, J; Linhart, A; Siranec, M; Marek, J; Blechova, K; Kamenik, M; Pazdernik, M; Pelouch, R; Coufal, Z; Mikulica, M; Griva, M; Jancova, E; Mikulcova, M; Taborsky, M; Precek, J; Jecmenova, M; Latal, J; Widimsky, J; Butta, T; Machacek, S; Vancata, R; Spinar, J; Holicka, M; Pow Chon Long, F; Anzules, N; Bajana Carpio, A; Largacha, G; Penaherrera, E; Moreira, D; Mahfouz, E; Elsafty, E; Soliman, A; Zayed, Y; Aboulenein, J; Abdel-Hay, M; Almaghraby, A; Abdelnaby, M; Ahmed, M; Hammad, B; Saleh, Y; Zahran, H; Elgebaly, O; Saad, A; Ali, M; Zeid, A; El 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Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43–3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06–2.13], p = 0.0210; 1-yr: HR 1.58[1.21–2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients