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1. Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project

Author: Belltall A, Zúñiga-Trejos S, Garrido-Cano I, Eroles P, Argente-Navarro MP, Buggy DJ, Díaz-Cambronero O, and Mazzinari G
Subjects: surgery, tumor, immunohistochemistry, cancer, perioperative opioid, opioid receptors, neoplasm
Abstract: Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes.; Methods: We investigated the normalized gene expression of , kappa, delta opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS).; Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes.; Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive. Copyright © 2022 Belltall, Zuniga-Trejos, Garrido-Cano, Eroles, Argente-Navarro, Buggy, Diaz-Cambronero and Mazzinari.
Published: 2022

2. A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit

Author: Kotfis, K., Wittebole, X., Jaschinski, U., Sole-Violan, J., Kashyap, R., Leone, M., Nanchal, R., Fontes, Le, Sakr, Y., Vincent, Jl, Tomas, E., Bibonge, Ea, Charra, B., Faroudy, M., Doedens, L., Farina, Z., Adler, D., Balkema, C., Kok, A., Alaya, S., Gharsallah, H., Muzha, D., Temelkov, A., Georgiev, G., Simeonov, G., Tsaryanski, G., Georgiev, S., Seliman, A., Vrankovic, S., Vucicevic, Z., Gornik, I., Barsic, B., Husedzinovic, I., Pavlik, P., Manak, J., Kieslichova, E., Turek, R., Fischer, M., Valkova, R., Dadak, L., Dostal, P., Malaska, J., Hajek, R., Zidkova, A., Lavicka, P., Starkopf, J., Kheladze, Z., Chkhaidze, M., Kaloiani, V., Medve, L., Sarkany, A., Kremer, I., Marjanek, Z., Tamasi, P., Krupnova, I., Vanags, I., Liguts, V., Pilvinis, V., Vosylius, S., Kekstas, G., Balciunas, M., Kolbusz, A., Kubler, A., Mielczarek, B., Mikaszewska-Sokolewicz, M., Tamowicz, B., Sulkowski, W., Smuszkiewicz, P., Pihowicz, A., Trejnowska, E., Hagau, N., Filipescu, D., Droc, G., Lupu, M., Nica, A., Stoica, R., Tomescu, D., Constantinescu, D., Zbaganu, Gv, Slavcovici, A., Bagin, V., Belsky, D., Palyutin, S., Shlyapnikov, S., Bikkulova, D., Gritsan, A., Natalia, G., Makarenko, E., Kokhno, V., Tolkach, A., Kokarev, E., Belotserkovskiy, B., Zolotukhin, K., Kulabukhov, V., Soskic, L., Palibrk, I., Jankovic, R., Jovanovic, B., Pandurovic, M., Bumbasirevic, V., Uljarevic, B., Surbatovic, M., Ladjevic, N., Slobodianiuk, G., Sobona, V., Cikova, A., Gebhardtova, A., Jun, C., Yunbo, S., Dong, U., Feng, S., Duan, M., Xu, Y., Xue, X., Gao, T., Xing, X., Zhao, X., Li, C., Gengxihua, G., Tan, H., Xu, J., Jiang, L., Tiehe, Q., Bingyu, Q., Shi, Q., Lv, Z., Zhang, L., Jingtao, L., Zhen, Z., Wang, Z., Wang, T., Yuhong, L., Zhai, Q., Chen, Y., Wang, C., Jiang, W., Ruilan, W., Xiaobo, H., Ge, H., Yan, T., Yuhui, C., Zhang, J., Jian-Hong, F., Zhu, H., Huo, F., Wang, Y., Zhuang, M., Ma, Z., Sun, J., Liuqingyue, L., Yang, M., Meng, J., Ma, S., Kang, Y., Yu, L., Peng, Q., Wei, Y., Zhang, W., Sun, R., Yeung, A., Wan, W., Sin, K., Lee, K., Wijanti, M., Widodo, U., Samsirun, H., Sugiman, T., Wisudarti, C., Maskoen, T., Hata, N., Kobe, Y., Nishida, O., Miyazaki, D., Nunomiya, S., Uchino, S., Kitamura, N., Yamashita, K., Hashimoto, S., Fukushima, H., Adib, Nn, Tai, L., Tony, B., Bigornia, R., Palo, J., Chatterjee, S., Tan, B., Kong, A., Goh, S., Lee, C., Pothirat, C., Khwannimit, B., Theerawit, P., Pornsuriyasak, P., Piriyapatsom, A., Mukhtar, A., Dsicu, Hamdy, An, Hosny, H., Ashraf, A., Mokhtari, M., Nowruzinia, S., Lotfi, A., Zand, F., Nikandish, R., Moghaddam, Om, Cohen, J., Sold, O., Sfeir, T., Hasan, A., Abugaber, D., Ahmad, H., Tantawy, T., Baharoom, S., Algethamy, H., Amr, A., Almekhlafi, G., Coskun, R., Sungur, M., Cosar, A., Gucyetmez, B., Demirkiran, O., Senturk, E., Ulusoy, H., Atalan, H., Serin, S., Kati, I., Alnassrawi, Z., Almemari, A., Krishnareddy, K., Kashef, S., Alsabbah, A., Poirier, G., Marshall, J., Herridge, M., Fernandez-Medero, R., Fulda, G., Banschbach, S., Quintero, J., Schroeder, E., Sicoutris, C., Gueret, R., Bauer, P., Wunderink, R., Jimenez, E., Ryan, A., Prince, D., Edington, J., Haren, F., Bersten, A., Hawkins, Dj, Kilminster, M., Sturgess, D., Ziegenfuss, M., O Connor, S., Lipman, J., Campbell, L., Mcallister, R., Roberts, B., Williams, P., Parke, R., Seigne, P., Freebairn, R., Nistor, D., Oxley, C., Young, P., Valentini, R., Wainsztein, N., Comignani, P., Casaretto, M., Sutton, G., Villegas, P., Galletti, C., Neira, J., Rovira, D., Hidalgo, J., Sandi, F., Caser, E., Thompson, M., Dias, Md, Fontes, L., Lunardi, M., Youssef, N., Lobo, S., Silva, R., Sales, J., Melo, Lmc, Oliveira, M., Fonte, M., Grion, C., Feijo, C., Rezende, V., Assuncao, M., Neves, A., Gusman, P., Dalcomune, D., Teixeira, C., Kaefer, K., Maia, I., Dantas, Vs, Filho, Rc, Amorim, F., Assef, M., Schiavetto, P., Houly, J., Bianchi, F., Dias, F., Avila, C., Gomez, J., Rego, L., Castro, P., Passos, J., Mendes, C., Mecatti, Gc, Ferrreira, M., Irineu, V., Guerreiro, M., Ugarte, S., Tomicic, V., Godoy, C., Samaniego, W., Escamilla, I., Castro, Lc, Duque, Gl, Diaz-Guio, D., Benitez, F., Urrego, Ag, Buitrago, R., Ortiz, G., Gaviria, Mv, Salas, D., Ramirez-Arce, J., Salgado, E., Morocho, D., Vergara, J., Sang, Mc, Carlos E. Orellana-Jimenez, Garrido, L., Diaz, O., Resiere, D., Osorio, C., La Vega, A., Carrillo, R., Sanchez, V., Villagomez, A., Zubieta, Rm, Sandia, M., Zalatiel, M., Poblano, M., Gonzalez, Dr, Arrazola, F., Francisco, Lj, Liamendys-Silva, Sa, Hernandez, M., Cadena, Dr, Islas, Il, Zarzavilla, Cb, Matos, A., Oyanguren, I., Cerna, J., Sierra, Rq, Jimenez, R., Castillo, L., Ocal, R., Sencan, A., Gianoni, Sm, Deicas, A., Hurtado, J., Burghi, G., Martinelli, A., Osten, I., Du Maine, C., Bhattacharyya, M., Bandyopadhyay, S., Yanamala, S., Gopal, P., Sahu, S., Ibrahim, M., Rathod, D., Mukundan, N., Dewan, A., Amin, P., Samavedam, S., Shah, B., Gurupal, D., Lahkar, B., Mandal, A., Sircar, M., Ghosh, S., Balasubramani, V., Kapadia, F., Vadi, S., Nair, K., Tripathy, S., Nandakumar, S., Sharma, J., Kar, A., Jha, S., Gurav, Kz, Patel, M., Bhaysar, A., Samaddar, D., Kulkarni, A., Hashmi, M., Ali, W., Nadeem, S., Indraratna, K., Margarit, A., Urbanek, P., Schlieber, J., Reisinger, J., Auer, U., Hartjes, A., Lerche, A., Janous, T., Kink, E., Krahulec, W., Smolle, K., Schueren, M., Thibo, P., Vanhoof, M., Ahmet, I., Gadisseux, P., Dufaye, P., Jacobs, O., Fraipont, V., Biston, P., Dive, A., Bouckaert, Y., Gilbert, E., Gressens, B., Pinck, E., Collin, V., Waele, J., Rimachi, R., Gusu, D., Decker, K., Mandianga, K., Heytens, L., Spapen, H., Olivier, V., Vandenheede, W., Rogiers, P., Kolodzeike, P., Kruse, M., Andersen, T., Harjola, V., Saarinen, K., Durocher, A., Moulront, S., Lepape, A., Losser, M., Cabaret, P., Kalaitzis, E., Zogheib, E., Charve, P., Francois, B., Lefrant, Jy, Beilouny, B., Forceville, X., Misset, B., Jacobs, F., Floccard, B., Payen, D., Wynckel, A., Castelain, V., Faure, A., Lavagne, P., Thierry, I., Moussa, M., Vieillard-Baron, A., Durand, M., Gainnier, M., Ichai, C., Arens, S., Hoffmann, C., Kaffarnik, M., Scharnofske, C., Voigt, I., Peckelsen, C., Weber, M., Gille, J., Lange, A., Schoser, G., Sablotzki, A., Bluethgen, A., Vogel, F., Tscheu, A., Fuchs, T., Wattenberg, M., Helmes, T., Scieszka, S., Heintz, M., Sakka, S., Kohler, J., Fiedler, F., Danz, M., Riessen, R., Kerz, T., Kersten, A., Tacke, F., Marx, G., Volkert, T., Schmutz, A., Nierhaus, A., Kluge, S., Abel, P., Janosi, R., Utzolino, S., Bracht, H., Toussaint, S., Peftoulidou, Mg, Myrianthefs, P., Armaganidis, A., Routsi, C., Xini, A., Mouloudi, E., Kokoris, I., Kyriazopoulos, G., Vlachos, S., Lavrentieva, A., Partala, P., Nakos, G., Moller, A., Stefansson, S., Barry, J., O Leary, R., Motherway, C., Faheem, M., Dunne, E., Donnelly, M., Konrad, T., Bonora, E., Achilli, C., Rossi, S., Castiglione, G., Penis, A., Albanese, D., Stocchetti, N., Citerio, G., Mozzoni, L., Sisillo, E., Negri, P., Savioli, M., Vecchiarelli, P., Puflea, F., Stankovic, V., Minoja, G., Montibeller, S., Calligaro, P., Sorrentino, R., Feri, M., Zambon, M., Colombaroli, E., Giarratano, A., Pellis, T., Capra, C., Antonelli, M., Gullo, A., Chelazzi, C., Capraris, A., Patroniti, N., Girardis, M., Franchi, F., Berlot, G., Buttigieg, M., Ponssen, H., Cate, Jt, Bormans, L., Husada, S., Buise, M., Hoven, B., Reidinga, A., Kuiper, M., Pickkers, P., Kluge, G., Den Boer, S., Kesecioglu, J., Leeuwen, H., Flaatten, H., Mo, S., Branco, V., Rua, F., Lafuente, E., Sousa, M., Catorze, N., Barros, M., Pereira, L., Oliveira, Av, Gomes, J., Gaspar, I., Pereira, M., Cymbron, M., Dias, A., Almeida, E., Beirao, S., Serra, I., Ribeiro, R., Povoa, P., Faria, F., Costa-E-Silva, Z., Nobrega, A., Fernandes, F., Gabriel, J., Voga, G., Rupnik, E., Kosec, L., Povsic, Mk, Osojnik, I., Tomic, V., Sinkovic, A., Gonzalez, J., Zavala, E., Valenzuela, Ap, Marina, L., Vidal-Cortes, P., Posada, I., Martin-Loeches, Ai, Guillen, Nm, Palomar, M., Sole-Violan, U., Torres, A., Gallego, Mg, Aguilar, G., Allue, Rm, Argueso, M., Parejo, M., Navarro, Mp, Jose, A., Nin, N., Lerma, Fa, Martinez, O., Lozano, Et, Lopez, Sa, Granda, Mp, Moreno, S., Llubia, C., Martos, Cd, Gonzalez-Arenas, P., Fernandez, Nl, Rueda, Bg, Pons, Ie, Cruza, N., Maroto, F., Estella, A., Ferrer, A., Fraile, Li, Quindos, B., Quintano, A., Tebar, M., Cardinal, I., Reyes, A., Rodriguez, A., Abella, A., Del Valle, Sg, Yus, S., Maseda, E., Berezo, U., Pedregosa, At, Laplaza, C., Ferrer, R., Rico-Feijoo, U., Rodriguez, M., Monedero, P., Eriksson, K., Lind, D., Chabanel, D., Zender, H., Heer, K., Frankenberger, B., Jakob, S., Mathew, S., Downes, R., Groba, Cb, Johnston, A., Meacher, R., Keays, R., Haji-Michael, P., Tyler, C., Ferguson, A., Jones, S., Tyl, D., Ball, A., Vogel, U., Booth, M., Downie, P., Watters, M., Brett, S., Garfield, M., Everett, L., Heenen, S., Dhir, S., Beardow, Z., Mostert, M., Brosnan, S., Pinto, N., Harris, S., Summors, A., Andrew, N., Rose, A., Appelboam, R., Davies, O., Vickers, E., Agarwal, B., Szakmany, T., Wimbush, S., Welters, I., Pearse, R., Hollands, R., Kirk-Bayley, U., Fletcher, N., Bray, B., Brealey, D., Intensive Care, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, UCL - (MGD) Services des soins intensifs, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], and University of Wisconsin School of Medicine and Public Health
Subjects: Adult, Male, medicine.medical_specialty, Critical Illness, Medizin, Audit, Critical Care and Intensive Care Medicine, Sepsis, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Epidemiology, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In patient, Hospital Mortality, Prospective Studies, Mortality, ComputingMilieux_MISCELLANEOUS, Outcome, Aged, computer.programming_language, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Critically ill, ICU, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Hospitalization, Intensive Care Units, Increased risk, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Observational study, Icon, business, computer
Abstract: Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world., Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure., Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying., Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. All rights reserved., C1 [Kotfis, Katarzyna] Pomeranian Med Univ, Dept Anaesthesiol Intens Therapy & Acute Intoxica, Szczecin, Poland., [Wittebole, Xavier] UCL, Clin Univ St Luc, Dept Crit Care, Brussels, Belgium., [Jaschinski, Ulrich] Klinikum Augsburg, Klin Anasthesiol & Operat Intens Med, Augsburg, Germany., [Sole-Violan, Jordi] Hosp Univ Gran Canaria Dr Negrin, Dept Intens Care, Las Palmas Gran Canaria, Spain., [Kashyap, Rahul] Mayo Clin, Dept Anesthesia Ei Perioperat Med, Rochester, MN USA., [Leone, Marc] Aix Marseille Univ, Hop Nord, AP HM, Serv Anesthesie & Reanimat, Marseille, France., [Nanchal, Rahul] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA., [Fontes, Luis E.] Hosp Alcides Carneiro, Petropolis Med Sch, Dept Intens Care & Evidence Based Med, Petropolis, Brazil., [Sakr, Yasser] Uniklinikum Jena, Dept Anesthesiol & Intens Care, Jena, Germany., [Vincent, Jean-Louis] Univ Libre Bruxelles, Erasme Univ Hosp, Dept Intens Care, Route Lenn 808, B-1070 Brussels, Belgium., [Tomas, E.] Clin Sagrada Esperanca, Luanda, Angola., [Bibonge, E. Amisi] Clin Univ Kinshasa, Kinshasa, DEM REP CONGO., [Charra, B.] Chu Ibn Rochd Casablanca, Casablanca, Morocco., [Faroudy, M.] Ibn Sina Hosp, Rabat, Morocco., [Doedens, L.] Chris Hani Baragwanath Acad Hosp, Soweto, South Africa., [Farina, Z.] Grays Hosp, Pietermaritzburg, South Africa., [Adler, D.] Sandton Medi Clin, Sandton, South Africa., [Balkema, C.] Tygerberg Hosp, Cape Town, South Africa., [Kok, A.] Union Hosp Alberton, Alberton, South Africa., [Alaya, S.] Bizerte Hosp, Bizerte, Tunisia., [Gharsallah, H.] Mil Hosp Tunis, Tunis, Tunisia., [Muzha, D.] Natl Trauma Ctr & Mil Hosp, Tirana, Albania., [Temelkov, A.] Alexandrovska Univ Hosp, Sofia, Bulgaria., [Georgiev, G.] Emergency Univ Hosp Pirogov, Sofia, Bulgaria., [Simeonov, G.] Tokuda Hosp Sofia, Sofia, Bulgaria., [Tsaryanski, G.] Uh St Ekaterina Sofia, Sofia, Bulgaria., [Georgiev, S.] Univ Hosp Obstet & Gynaecol, Sofia, Bulgaria., [Seliman, A.] Univ Hosp Sveta Marina Varna, Varna, Bulgaria., [Vrankovic, S.] Gen Hosp Siben, Shibenik, Croatia., [Vucicevic, Z.] Univ Hosp Ctr Sestre Milosrdnice, Zagreb, Croatia., [Gornik, I] Univ Hosp Ctr Zagreb, Zagreb, Croatia., [Barsic, B.] Univ Hosp Infect Dis, Zagreb, Croatia., [Husedzinovic, I] Univ Hosp Dubrava, Zagreb, Croatia., [Pavlik, P.] Ctr Cardiovasc & Transplant Surg, Prague, Czech Republic., [Manak, J.] Charles Univ Hosp, Prague, Czech Republic., [Kieslichova, E.] IKEM, Prague, Czech Republic., [Turek, R.] KNTB Zlin AS, Prague, Czech Republic., [Fischer, M.] Krajska Nemocnice Liberec, Prague, Czech Republic., [Valkova, R.] Masarykova Nemocnice V Usti Labem, Labem, Czech Republic., [Dadak, L.] St Annes Univ Hosp Brno, Brno, Czech Republic., [Dostal, P.] Univ Hosp Haradec Kralove, Haradec Kralove, Czech Republic., [Malaska, J.] Univ Hosp Brno, Brno, Czech Republic., [Hajek, R.] Univ Hosp Olomouc, Olomouc, Czech Republic., [Zidkova, A.] Univ Hosp Plzen, Plzen, Czech Republic., [Lavicka, P.] Charles Univ Hosp Plzen, Plzen, Czech Republic., [Starkopf, J.] Tartu Univ Hosp, Tartu, Estonia., [Kheladze, Z.] Crit Care Med Inst, Gainesville, Georgia., [Chkhaidze, M.] Jo Ann Med Ctr, Tbilisi, Georgia., [Kaloiani, V] Kipshidze Cent Univ Hosp, Tbilisi, Georgia., [Medve, L.] Dr Kenessey Albert Hosp, Balassagyarmat, Hungary., [Sarkany, A.] Fejer Cty St George Teaching Hosp, Szekesfehervar, Hungary., [Kremer, I] Flor Ferenc Cty Hosp, Budapest, Hungary., [Marjanek, Z.] Javorszky Odon Hosp, Vac, Hungary., [Tamasi, P.] Peterfy Hosp Budapest, Budapest, Hungary., [Krupnova, I] Infectol Ctr Latvia, Riga, Latvia., [Vanags, I] Paul Stradins Clin Univ Hosp, Riga, Latvia., [Liguts, V] Riga East Clin Univ Hosp, Riga, Latvia., [Pilvinis, V] Hosp Lithuanian Univ Hlth Sci Kauno Klinikos, Kaunas, Lithuania., [Vosylius, S.] Vilnius Univ Hosp, Vilnius, Lithuania., [Kekstas, G.] HSICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Balciunas, M.] CICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Kolbusz, A.] Csk Mswia, Warsaw, Poland., [Kubler, A.] Med Univ, Wroclaw, Poland., [Mielczarek, B.] Med Univ Wroclaw, Wroclaw, Poland., [Mikaszewska-Sokolewicz, M.] Med Univ Warsaw, Warsaw, Poland., [Kotfis, K.] Pomeranian Med Univ, Szczecin, Poland., [Tamowicz, B.] Reg Hosp Poznan, Poznan, Poland., [Sulkowski, W.] Szpital Powiatowy W Ostrowi Mazowieckiej, Ostrow Mazowiecka, Poland., [Smuszkiewicz, P.] Univ Hosp, Poznan, Poland., [Pihowicz, A.] Wojewodzki Szpital Zakazny, Torun, Poland., [Trejnowska, E.] Wojewodzkie Ctr Med, Warsaw, Poland., [Hagau, N.] Emergency Cty Hosp Cluj, Cluj Napoca, Romania., [Filipescu, D.] Emergency Inst Cardiovasc Dis, Bucharest, Romania., [Droc, G.] Fundeni Clin Inst, Bucharest, Romania., [Lupu, M.] Galati Hosp, Bucharest, Romania., [Nica, A.] Lnbi Prof Dr Matei Bals, Bucharest, Romania., [Stoica, R.] Inst Pulmonol Marius Nasta, Bucharest, Romania., [Tomescu, D.] Inst Clin Fundeni, Bucharest, Romania., [Constantinescu, D.] Sfantul Pantelimon Hosp, Bucharest, Romania., [Zbaganu, G. Valcoreanu] Spitalul Cf 2 Bucuresti, Bucharest, Romania., [Slavcovici, A.] Iuliu Hatieganu Univ Med & Pharm, Teaching Hosp Infect Dis, Cluj Napoca, Romania., [Bagin, V] City Clin Hosp 40, St Petersburg, Russia., [Belsky, D.] City Hosp 40, St Petersburg, Russia., [Palyutin, S.] Clin Hosp NVNV Solovyev, Yaroslavl, Russia., [Shlyapnikov, S.] Emergency Res Inst NA Djanelidze, St Petersburg, Russia., [Bikkulova, D.] Fed Res Ctr Paediat Haematol Oncol & Immunol, Moscow, Russia., [Gritsan, A.] Krasnoyarsk State Med Univ, Krasnoyarsk Reg Hosp, Krasnoyarsk, Russia., [Natalia, G.] Med Assoc Novaya Bolnitsa, Ekaterinburg, Russia., [Makarenko, E.] Mil Med Acad, Ekaterinburg, Russia., [Kokhno, V] Novosibirsk Med Univ, Novosibirsk, Russia., [Tolkach, A.] Omsk Reg Clin Hosp, Omsk, Russia., [Kokarev, E.] Railway Hosp Khabarovsk, Khabarovsk, Russia., [Belotserkovskiy, B.] St Alexy Hosp, St Louis, France., [Zolotukhin, K.] State Dist Hosp, Moscow, Russia., [Kulabukhov, V] Vishnevsky Inst Surg, Moscow, Russia., [Soskic, L.] Clin Ctr Serbia, Clin Cardiac Surg, Belgrade, Serbia., [Palibrk, I] Clin Ctr Serbia, Clin Digest Surg, Belgrade, Serbia., [Jankovic, R.; Jovanovic, B.] Clin Ctr Nis, Clin Vasc Surg, Nish, Serbia., [Pandurovic, M.] Clin Ctr Serbia, Emergency Ctr, Belgrade, Serbia., [Bumbasirevic, V] Clin Ctr Belgrade, Emergency Ctr, Belgrade, Serbia., [Uljarevic, B.] Gen Univ Hosp, Belgrade, Serbia., [Surbatovic, M.] Mil Med Acad, Belgrade, Serbia., [Ladjevic, N.] Urol Hosp, Belgrade, Serbia., [Slobodianiuk, G.] Dist Hosp, Bratislava, Slovakia., [Sobona, V] Fac Hosp, Bratislava, Slovakia., [Cikova, A.] Univ Hosp Bratislava, Hosp Ruzinov ICU, Bratislava, Slovakia., [Gebhardtova, A.] Univ Hosp Ruzinov Bratislava, Bratislava, Slovakia., [Jun, C.] Qingdao Univ, Tertiary Hosp, Qingdao, Shandong, Peoples R China., [Yunbo, S.] Qingdao Univ, Affiliated Hosp, Med Coll, Qingdao, Shandong, Peoples R China., [Dong, U.] Beijing Canc Hosp, Beijing Inst Canc Res, Beijing, Peoples R China., [Feng, S.] Beijing Chaoyang Hosp, Beijing, Peoples R China., [Duan, M.] Beijing Friendship Hosp, Beijing, Peoples R China., [Xu, Y.] Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China., [Xue, X.] Beijing Univ Peoples Hosp, Beijing, Peoples R China., [Gao, T.] Beijing Luhe Hosp, Beijing, Peoples R China., [Xing, X.] Chinese Acad Med Sci, Canc Hosp, Beijing, Peoples R China., [Zhao, X.] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing, Peoples R China., [Li, C.] Peoples Hosp, Chuxiong, Yunnan, Peoples R China., [Gengxihua, G.] Donge Cty Peoples Hosp Shandong Prov, Liaocheng, Shandong, Peoples R China., [Tan, H.] Chinese Acad Med Sci, Fu Wai Hosp, Beijing, Peoples R China., [Xu, J.] Fujian Prov Hosp, Fuzhou, Fujian, Peoples R China., [Jiang, L.] Capital Med Univ, Fuxing Hosp, Beijing, Peoples R China., [Tiehe, Q.] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China., [Bingyu, Q.] Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China., [Shi, Q.] Xi An Jiao Tong Univ, Coll Med, Xian, Shaanxi, Peoples R China., [Lv, Z.] Kunming Third Peoples Hosp, Kunming, Yunnan, Peoples R China., [Zhang, L.] Lanzhou Univ, Hosp 2, Lanzhou, Gansu, Peoples R China., [Jingtao, L.] 309th Hosp, Beijing, Peoples R China., [Zhen, Z.] China Med Univ, Hosp 1, Beijing, Peoples R China., [Wang, Z.] Peking Univ, Shougang Hosp, Beijing, Peoples R China., [Wang, T.] Peking Univ, Hosp 3, Beijing, Peoples R China., [Yuhong, L.] Pla Navy Gen Hosp, Beijing, Peoples R China., [Zhai, Q.] Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China., [Chen, Y.] Jiaotong Univ, Affiliated Med Sch, Ruijin Hosp, Shanghai, Peoples R China., [Wang, C.] Shandong Prov Hosp, Jinan, Shandong, Peoples R China., [Jiang, W.] Shanghai 10th Peoples Hosp, Shanghai, Peoples R China., [Ruilan, W.] Shanghai First Peoples Hosp, Shanghai, Peoples R China., [Chen, Y.; Xiaobo, H.] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China., [Ge, H.] Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China., [Yan, T.] Affiliated Guiyang Med Coll, Guiyang, Guizhou, Peoples R China., [Yuhui, C.] Fudan Univ, Peoples Hosp Shanghai 5, Shanghai, Peoples R China., [Zhang, J.] Dalian Med Univ, Affiliated Hosp 1, Dalian, Peoples R China., [Jian-Hong, F.] Suzhou Univ, Affiliated Hosp 1, Suzhou, Peoples R China., [Zhu, H.] Xinjiang Med Univ, Affiliated Hosp 1, Urumqi, Peoples R China., [Huo, F.; Wang, Y.] Jilin Univ, Hosp 1, Changchun, Jilin, Peoples R China., [Li, C.] First Peoples Hosp Kunming, Kunming, Yunnan, Peoples R China., [Zhuang, M.] Gen Hosp Shenyang Mil Reg, Shenyang, Liaoning, Peoples R China., [Ma, Z.] Peoples Hosp Cangzhou, Cangzhou, Peoples R China., [Sun, J.] Jilin Univ, Hosp 2, Changchun, Jilin, Peoples R China., [Liuqingyue, L.] Second Peoples Hosp Liaocheng City Shandong Prov, Liaocheng, Shandong, Peoples R China., [Yang, M.] Third Xiangya Hosp, Changsha, Hunan, Peoples R China., [Meng, J.] Tongde Hosp Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China., [Ma, S.] Tongji Univ, Shanghai East Hosp, Shanghai, Peoples R China., [Kang, Y.] West China Hosp, Scu, Peoples R China., [Yu, L.] Wuhan Ctr Hosp, Wuhan, Hubei, Peoples R China., [Peng, Q.] Xiangya Hosp, Changsha, Hunan, Peoples R China., [Wei, Y.] Yantai Yuhuangding Hosp, Yantai, Peoples R China., [Zhang, W.] Yantaishan Hosp, Yantai, Shandong, Peoples R China., [Sun, R.] Zhejiang Prov Peoples Hosp, Hangzhou, Zhejiang, Peoples R China., [Yeung, A.] Pamela Youde Nethersole Eastern Hosp, Hong Kong, Peoples R China., [Wan, W.] Princess Margaret Hosp, Hong Kong, Peoples R China., [Sin, K.] Queen Elizabeth Hosp, Hong Kong, Peoples R China., [Lee, K.] United Christian Hosp Hong Kong SAR, Hong Kong, Peoples R China., [Wijanti, M.] Anestesi, Yogyakarta, Indonesia., [Widodo, U.] Pku Muhammadiyah Bantu, Yogyakarta, Indonesia., [Samsirun, H.] Rd Mattaher Hosp Jambi, Jambi City, Indonesia., [Sugiman, T.] Rumah Sakit Pantai Lndah Kapuk, North Jakarta, Indonesia., [Wisudarti, C.] Sardjito Hosp, Yogyakarta, Indonesia., [Maskoen, T.] Sch Med Unpad, Hasan Sadikin Hosp, Bandung, Indonesia., [Hata, N.] Nippon Med Sch, Chiba Hokusoh Hosp, Inzai, Japan., [Kobe, Y.] Chiba Univ Hosp, Chiba, Japan., [Nishida, O.] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan., [Miyazaki, D.] Japanese Red Cross Maebashi Hosp, Maebashi, Gumma, Japan., [Nunomiya, S.] Jichi Med Univ Hosp, Shimotsuke, Japan., [Uchino, S.] Jikei Univ, Sch Med, Tokyo, Japan., [Kitamura, N.] Kimitsu Chuo Hosp, Kisarazu, Japan., [Yamashita, K.] Kochi Med Sch, Nankoku, Kochi, Japan., [Hashimoto, S.] Kyoto Prefectural Univ Med, Kyoto, Japan., [Fukushima, H.] Nara Med Univ Hosp, Kashihara, Nara, Japan., [Adib, N. Nik] Hosp Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia., [Tai, L.] Kuala Lumpur Hosp, Kuala Lumpur, Malaysia., [Tony, B.] Queen Elizabeth Hosp 2, Kota Kinabalu, Malaysia., [Bigornia, R.] Cebu Velez Gen Hosp, Cebu, Philippines., [Bigornia, R.] Perpetual Succour Hosp, Cebu, Philippines., [Palo, J.] Med City, Pasig, Philippines., [Chatterjee, S.] Alexandra Hosp, Singapore, Singapore., [Tan, B.] Natl Univ Hlth Syst, Singapore, Singapore., [Kong, A.] Singapore Gen Hosp, Singapore, Singapore., [Goh, S.] Tan Tock Seng Hosp, Singapore, Singapore., [Lee, C.] Natl Taiwan Univ Hosp, Taipei, Taiwan., [Pothirat, C.] Chiaingmai Univ, Maharaj Nakorn Chiangmai Hosp, Chiang Mai, Thailand., [Khwannimit, B.] Prince Songkla Univ, Hat Yai, Thailand., [Theerawit, P.] Ramathibodi Hosp, Bangkok, Thailand., [Pornsuriyasak, P.] Ramathibodi Hosp, Somdech Phra Debaratana Med Ctr, Bangkok, Thailand., [Piriyapatsom, A.] Mahidol Univ, Siriraj Hosp, Bangkok, Thailand., [Mukhtar, A.] Cairo Univ, Giza, Egypt., [Dsicu] Demerdash Surg Intens Care Unit, Cairo, Egypt., [Hamdy, A. Nabil] Ain Shams Fac Med, Cairo, Egypt., [Hosny, H.] Zaitoun Specialized Hosp, Cairo, Egypt., [Ashraf, A.] Gums, Tehran, Iran., [Mokhtari, M.] Sbums, Imam Hossein Hosp, Tehran, Iran., [Nowruzinia, S.] Imamreza Hosp, Mashhad, Razavi Khorasan, Iran., [Lotfi, A.] Laleh Hosp, Tehran, Iran., [Zand, F.] Shiraz Anesthesiol & Crit Care Res Ctr, Shiraz, Iran., [Nikandish, R.] Shiraz Univ Med Sci, Shiraz, Iran., [Moghaddam, O. Moradi] Tehran Med Sci Univ, Tehran, Iran., [Cohen, J.] Rabin Med Ctr, Petah Tiqwa, Israel., [Sold, O.] Sourasky Tel Aviv Med Ctr, Tel Aviv, Israel., [Sfeir, T.] Ctr Hosp Nord, Ettelbruck, Luxembourg., [Hasan, A.] Sohar Hosp, Sohar, Oman., [Abugaber, D.] Specialized Arab Hosp, Nablus, Palestine., [Ahmad, H.] Almana Gen Hosp, Khobar, Saudi Arabia., [Tantawy, T.] KFSHRC, Riyadh, Saudi Arabia., [Baharoom, S.] King Abdulaziz Med City Riyadh, Riyadh, Saudi Arabia., [Algethamy, H.] King Abdulaziz Univ, Jeddah, Saudi Arabia., [Amr, A.] King Saud Med City, Riyadh, Saudi Arabia., [Almekhlafi, G.] Riyadh Mil Hosp, Riyadh, Saudi Arabia., [Coskun, R.] Erciyes Univ, Med Fac, Kayseri, Turkey., [Sungur, M.] Erciyes Univ, Med Sch, Kayseri, Turkey., [Cosar, A.] Gulhane Mil Med Acad, Ankara, Turkey., [Gucyetmez, B.] Int Hosp, Istanbul, Turkey., [Demirkiran, O.] Istanbul Univ, Cerrahpasa Med Sch Hosp, Istanbul, Turkey., [Senturk, E.] Istanbul Univ, Istanbul Med Fac, Istanbul, Turkey., [Ulusoy, H.] Karadeniz Tech Univ, Med Fac, Trabzon, Turkey., [Atalan, H.] Mem Atasehir Hosp, Istanbul, Turkey., [Serin, S.] Pamukkale Univ, Denizli, Turkey., [Kati, I] Yuzuncu Yil Univ, Med Fac, Van, Turkey., [Alnassrawi, Z.] Dubai Hosp, Dubai, U Arab Emirates., [Almemari, A.] Mafraq Hosp, Abu Dhabi, U Arab Emirates., [Krishnareddy, K.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates., [Kashef, S.] Tawam Hosp, Al Ain, U Arab Emirates., [Alsabbah, A.] City Hosp, Dubai, U Arab Emirates., [Poirier, G.] Hop Charles Lemoyne, Longueuil, PQ, Canada., [Marshall, J.] St Michaels Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Gen Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Western Hosp, Toronto, ON, Canada., [Fernandez-Medero, R.] San Juan Hosp, San Juan, PR USA., [Fulda, G.] Christiana Care Hlth Syst, Newark, DE USA., [Banschbach, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA., [Quintero, J.] El Camino Hosp, Mountain View, CA USA., [Schroeder, E.] George Washington Hosp, Washington, DC USA., [Sicoutris, C.] Hosp Univ Penn, Philadelphia, PA 19104 USA., [Gueret, R.] John H Stroger Hosp Cook Cty, Chicago, IL USA., [Kashyap, R.] Mayo Clin, CCM, Rochester, MN USA., [Bauer, P.] Mayo Clin, PCC, Rochester, MN USA., [Nanchal, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA., [Wunderink, R.] Northwestern Mem Hosp, Chicago, IL 60611 USA., [Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA., [Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA., [Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA., [Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia., [Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia., [Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia., [Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia., [Hawkins, D. J.] Joondalup Hlth Campus, Joondalup, WA, Australia., [Kilminster, M.] Lismore Base Hosp, Lismore, NSW, Australia., [Sturgess, D.] Mater Adult Hosp, South Brisbane, Qld, Australia., [Ziegenfuss, M.] Prince Charles Hosp, Brisbane, Qld, Australia., [O'Connor, S.] Royal Adelaide Hosp, Adelaide, SA, Australia., [Lipman, J.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia., [Campbell, L.] Royal Darwin Hosp, Tiwi, NT, Australia., [Mcallister, R.] Royal Hobart Hosp, Hobart, Tas, Australia., [Roberts, B.] Sir Charles Gairdner Hosp, Nedlands, WA, Australia., [Williams, P.] Queen Elizabeth Hosp, Woodville, SA, Australia., [Parke, R.] Auckland Dist Hlth Board, Auckland, New Zealand., [Seigne, P.] Christchurch Hosp, Christchurch, New Zealand., [Freebairn, R.] Hawkes Bay Hosp, Hastings, New Zealand., [Nistor, D.] Palmerston North Hosp, Midcent Hlth, Palmerston North, New Zealand., [Oxley, C.] Middlemore Hosp, Auckland, New Zealand., [Young, P.] Wellington Hosp, Wellington, New Zealand., [Valentini, R.] Cemic, Buenos Aires, DF, Argentina., [Wainsztein, N.] Fleni, Buenos Aires, DF, Argentina., [Comignani, P.] Hosp Aleman, Buenos Aires, DF, Argentina., [Casaretto, M.] Hosp Cent San Isidro, Buenos Aires, DF, Argentina., [Sutton, G.] Hosp Fernandez, Buenos Aires, DF, Argentina., [Villegas, P.] Hosp Francisco Lopez Lima Area Programa Gen Roca, Gen Roca, Argentina., [Galletti, C.] Sanatorio Allende, Cordoba, Argentina., [Neira, J.] Sanatorio Trinidad Palermo, Buenos Aires, DF, Argentina., [Rovira, D.] Sanatorio Julio Corzo Rosario, Rosario, Santa Fe, Argentina., [Hidalgo, J.] Karl Heusner Mem Hosp, Belize City, Belize., [Hidalgo, J.] Belize Healthcare Partner, Belize City, Belize., [Sandi, F.] Hosp Obrero 1, La Paz, Bolivia., [Caser, E.] Cias Unimed Vitoria, Vitoria, ES, Brazil., [Thompson, M.] Evangelical Hosp Cachoeiro De Itapemirim, Cachoeiro De Itapemirim, Brazil., [D'agostino Dias, M.] Hosp 9 Julho, Sao Paulo, Brazil., [Fontes, L.] Hosp Alcides Carneiro, Petropolis, Brazil., [Lunardi, M.] Hosp Clin Luzia De Pinho Melo, Mogi Das Cruzes, Brazil., [Youssef, N.] Hosp Nacoes Curitiba, Curitiba, Parana, Brazil., [Lobo, S.] Hosp Base Famerp, Sao Jose Do Rio Preto, Brazil., [Silva, R.] Hosp Clin Niteroi, Niteroi, RJ, Brazil., [Sales Jr, J.] Hosp Clin Padre Miguel, Rio De Janeiro, Brazil., [Madeira Campos Melo, L.] Hosp Terapia Intens, Sao Paulo, Brazil., [Oliveira, M.] Hosp Trabalhador, Curitiba, Parana, Brazil., [Fonte, M.] Hosp Esperanza, Olinda, PE, Brazil., [Grion, C.] Hosp Evangel Londrina, Londrina, Brazil., [Feijo, C.] Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil., [Rezende, V] Hosp Geral Roraima, Boa Vista, Brazil., [Assuncao, M.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil., [Neves, A.] Hosp Mater Dei, Belo Horizonte, MG, Brazil., [Gusman, P.; Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil., [Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil., [Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil., [Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil., [Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil., [Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil., [Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil., [Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil., [Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil., [Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil., [Houly, J.] Hosp Santapaula, Sao Paulo, Brazil., [Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil., [Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil., [Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil., [Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil., [Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil., [Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil., [Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil., [Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil., [Grion, C.] Hosp Univ Londrina, Londrina, Brazil., [Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil., [Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil., [Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil., [Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil., [Ugarte, S.] Clin Indisa, Providencia, Chile., [Tomicic, V] Clin Las Lilas, Providencia, Chile., [Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile., [Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile., [Escamilla, I] Hosp El Pino, San Bernardo, Chile., [Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile., [Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia., [Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia., [Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia., [Benitez, F.] Clin La Estancia SA, Popayan, Colombia., [Guerra Urrego, A.] Clin Medellin, Medellin, Colombia., [Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia., [Ortiz, G.] Hosp Santa Clara, Bogota, Colombia., [Villalba Gaviria, M.] Hosp Univ Fdn Santa Fe De Bogota, Bogota, Colombia., [Salas, D.] Calderon Guardia Hosp, San Jose, Costa Rica., [Ramirez-Arce, J.] Hosp Dr Rafael Angel Varlderon Guardia Ccss, San Jose, Costa Rica., [Salgado, E.] Clin La Merced, Quito, Ecuador., [Morocho, D.] Hosp Eugenio Espejo, Quito, Ecuador., [Vergara, J.] Hosp Luis Vernaza, Quito, Ecuador., [Chung Sang, M.] Shdug Sistema Hosp Docente De La Univ Guayaquil, Quito, Ecuador., [Orellana-Jimenez, C.] Gen Hosp, San Salvador, El Salvador., [Garrido, L.] Hosp Ctr Med, Guatemala City, Guatemala., [Diaz, O.] Inst Hondureno Seguro Social, La Ceiba, Honduras., [Resiere, D.] Ctr Hosp Univ Ft De France, Fort De France, Martinique, France., [Osorio, C.] Ctr Estatal Cuidados Crit, Salamanca, Mexico., [De La Vega, A.] Ctr Med Nacl 20 Noviembre Issste, Mexico City, DF, Mexico., [Carrillo, R.] Fdn Clin Med Sur, Mexico City, DF, Mexico., [Sanchez, V] Hosp San Jose TEC Monterrey, Monterrey, Mexico., [Villagomez, A.] Hosp 1 Octubre, Issste, Mexico., [Martinez Zubieta, R.] Hosp Espanol Mexico, Mexico City, DF, Mexico., [Sandia, M.] Hosp Gen Ajusco Medio, Mexico City, DF, Mexico., [Zalatiel, M.] Hosp Gen Guadalupe Victoria, Texcoco, Mexico., [Poblano, M.] Hosp Juarez Mexico, Mexico City, DF, Mexico., [Rodriguez Gonzalez, D.] Hosp Civil Guadalajara, Hspitaljuan I Menchaca, Guadalajara, Jalisco, Mexico., [Arrazola, F.; Juan Francisco, L.] Inst Mexicano Seguro Social, Mexico City, DF, Mexico., [Liamendys-Silva, S. A.] Inst Nacl Cancerol, Mexico City, DF, Mexico., [Hernandez, M.] ISSSTE Guerra Moya, Mexico City, DF, Mexico., [Hernandez, M.] Med Ctr ISSEMYM Toluca, Mexico City, DF, Mexico., [Rodriguez Cadena, D.] Mixta, Mexico City, DF, Mexico., [Lopez Islas, I.] Secretaria Salud Dist Fed, Mexico City, DF, Mexico., [Ballesteros Zarzavilla, C.] Hosp Santo Comas, Panama City, Panama., [Matos, A.] Social Secur Hosp, La Chorrera, Panama., [Oyanguren, I] Clin Anglo Amer, Lima, Peru., [Cerna, J.] Essalud, Lima, Peru., [Quispe Sierra, R.] Hosp Nacl Dos De Mayo, Lima, Peru., [Jimenez, R.] Hosp Rebagliati, Lince Dist, Peru., [Castillo, L.] Inst Nacl Enfermedades Neoplas, Surquillo, Peru., [Ocal, R.] Gulhane Med Fac, Istanbul, Turkey., [Sencan, A.] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey., [Gianoni, S. 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Zirpe] Ruby Hall Pune, Pune, Maharashtra, India., [Patel, M.] Saifee Hosp, Mumbai, Maharashtra, India., [Bhaysar, A.] Spandan Multispecial Hosp, Vadodara, India., [Samaddar, D.] Tata Main Hosp, Jamshedpur, Jharkhand, India., [Kulkarni, A.] Tata Mem Hosp, Mumbai, Maharashtra, India., [Hashmi, M.] Aga Khan Univ, Karachi, Pakistan., [Ali, W.] Hearts Int Hosp, Rawalpindi, Pakistan., [Nadeem, S.] Liaquat Natl Hosp, Karachi, Pakistan., [Indraratna, K.] Sri Jayewardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka., [Margarit, A.] Hosp Nostra Senyora Meritxell, Les Escaldes, Andorra., [Urbanek, P.] Akh Wien, Vienna, Austria., [Schlieber, J.] Allgemeines & Orthopad Landeskrankenhaus Stolzalp, Stolzalpe, Austria., [Reisinger, J.] Barmherzige Schwestern Linz, Linz, Austria., [Auer, U.] Gen Hosp Braunau, Braunau, Austria., [Hartjes, A.] Krankenhaus D Barmherzigen Schwestern Ried II, Ried Im Innkreis, Austria., [Lerche, A.] Krankenhaus Floridsdorf, Vienna, Austria., [Janous, T.] LK Gmund Waidhofen Thaya Zwettl, Standort Zwettl, Austria., [Kink, E.] LKH Horgas Enzenbach, Gratwein, Austria., [Krahulec, W.] LKH West, Graz, Austria., [Smolle, K.] Univ Hosp, Graz, Austria., [Van der Schueren, M.] AZ Groeninge Kortrijk, Kortrijk, Belgium., [Thibo, P.] AZ Jan Palfijn Gent, Ghent, Belgium., [Vanhoof, M.] AZ Turnhout, Turnhout, Belgium., [Ahmet, I] Bracops Anderlecht, Anderlecht, Belgium., [Gadisseux, P.] Ctr Hosp Mouscron, Mouscron, Belgium., [Dufaye, P.] CH Peltzer La Tourelle, Verviers, Belgium., [Jacobs, O.] Chirec Edith Cavell, Auderghem, Belgium., [Fraipont, V] CHR Citadelle, Liege, Belgium., [Biston, P.] CHU Charleroi, Charleroi, Belgium., [Dive, A.] CHU Mt Godinne, Yvoir, Belgium., [Bouckaert, Y.] CHU Tivoli, La Louviere, Belgium., [Gilbert, E.] CHwapi, Tournai, Belgium., [Gressens, B.] Clin St Pierre Ottignies, Ottignies, Belgium., [Pinck, E.] Clin Maternite St Elisabeth, Namur, Belgium., [Collin, V] Clin Europe St Michel, Etterbeek, Belgium., [Vincent, J. L.] Erasme Univ Hosp, Anderlecht, Belgium., [De Waele, J.] Ghent Univ Hosp, Ghent, Belgium., [Rimachi, R.] Moliere Hosp, Forest, Belgium., [Gusu, D.] Notre Dame, Brussels, Belgium., [De Decker, K.] Onze Lieve Vrouw Hosp, Aalst, Belgium., [Mandianga, K.] Ixelles Hosp, Ixelles, Belgium., [Heytens, L.] Sint Augustinus, Antwerp, Belgium., [Wittebole, X.] St Luc Univ Hosp UCL, Brussels, Belgium., [Spapen, H.] UZ Brussel, Brussels, Belgium., [Olivier, V] Vivalia Site Libramt, Libramont, Belgium., [Vandenheede, W.] VZW Gezondheidszorg Oostkust Knokke Heist, Knokke Heist, Belgium., [Rogiers, P.] ZNA Middelheim, Antwerp, Belgium., [Kolodzeike, P.] Herning Hosp, Herning, Denmark., [Kruse, M.] Hjoerring Hosp, Hjorring, Denmark., [Andersen, T.] Vejle Hosp, Vejle, Denmark., [Harjola, V] Helsinki Univ Cent Hosp, Helsinki, Finland., [Saarinen, K.] Seinajoki Cent Hosp, Seinajoki, Finland., [Leone, M.] Aix Marseille Univ, Hop Nord, Marseille, France., [Durocher, A.] Calmette Hosp, Lille, France., [Moulront, S.] Ctr Hosp Dunkerque, Dunkerque, France., [Lepape, A.] Ctr Hosp Lyon Sud, Lyon, France., [Losser, M.] CHU Nancy Brabois, Nancy, France., [Cabaret, P.] CH St Philibert, GHICL, Lille, France., [Kalaitzis, E.] CHR Dax, Dax, France., [Zogheib, E.] CHU Amiens, Amiens, France., [Charve, P.] CHU Dijon, Dijon, France., [Francois, B.] CHU Dupuytren, Limoges, France., [Lefrant, J. Y.] CHU Nimes, Nimes, France., [Beilouny, B.] Ctr Hosp Troyes, Troyes, France., [Forceville, X.] Ctr Hosp Meaux, Grp Hosp Est Francilien, Meaux, France., [Misset, B.] Grp Hosp Paris St Joseph, Paris, France., [Jacobs, F.] Hop Antoine Beclere, Clamart, France., [Floccard, B.] Hop Edouard Herriot, Lyon, France., [Payen, D.] Hop Lariboisere, AP HP, Paris, France., [Wynckel, A.] Hop Maison Blanche, Reims, France., [Castelain, V] Hop Univ Strasbourg, Strasbourg, France., [Faure, A.] Hosp Civils Lyon, Lyon, France., [Lavagne, P.] CHU Grenoble, Grenoble, France., [Thierry, I] CHU Nantes, Nantes, France., [Moussa, M.] CHRU Lille, Reanimat Chirurg Cardiovasc, Lille, France., [Vieillard-Baron, A.] Univ Hosp Ambroise Pare, Boulogne, France., [Durand, M.] Univ Hosp Grenoble, La Tronche, France., [Gainnier, M.] Univ Hosp Marseille, Marseille, France., [Ichai, C.] Univ Nice, Nice, France., [Arens, S.] Alexianer Krefeld Gmbh, Krefeld, Germany., [Hoffmann, C.] Charite Hochschulmed Berlin, Berlin, Germany., [Kaffarnik, M.] Charite, Berlin, Germany., [Scharnofske, C.] Diakoniekrankenhaus Henriettenstiftung Gmbh, Hannover, Germany., [Voigt, I] Elisabeth Krankenhaus Essen, Essen, Germany., [Peckelsen, C.] Munich Municipal Hosp Grp, Harlaching Hosp, Munich, Germany., [Weber, M.] Helios St Johannes Klin, Duisburg, Germany., [Gille, J.] Hosp St Georg Leipzig, Leipzig, Germany., [Lange, A.] Klin Hennigsdorf Oberhavel Kliniken Gmbh, Hennigsdorf, Germany., [Schoser, G.] Klin Tettnang, Tettnang, Germany., [Sablotzki, A.] Klinikum St Georg Leipzig, Leipzig, Germany., [Jaschinski, U.; Bluethgen, A.] Klinikum Augsburg, Augsburg, Germany., [Vogel, F.] Klinikum Bremen Mitte, Bremen, Germany., [Tscheu, A.] Klinikum Bremen Ost, Bremen, Germany., [Fuchs, T.] Klinikum Heidenheim, Heidenheim, Germany., [Wattenberg, M.] Klinikum Links Weser Gmbh, Bremen, Germany., [Helmes, T.] Klinikum Luedenscheid, Luedenscheid, Germany., [Scieszka, S.] Krankenhaus Neuwerk, Monchengladbach, Germany., [Heintz, M.] Marienkrankenhaus Schwerte, Schwerte, Germany., [Sakka, S.] Med Ctr Cologne Merheim, Cologne, Germany., [Kohler, J.] Schwarzwald Baar Klinikum Villingen Schwenningen, Villingen Schwenningen, Germany., [Fiedler, F.] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany., [Danz, M.] St Martinus Hosp Olpe, Olpe, Germany., [Sakr, Y.] Uniklinikum Jena, Jena, Germany., [Riessen, R.] Univ Klinikum Tubingen, Tubingen, Germany., [Kerz, T.] Univ Med Mainz, Mainz, Germany., [Kersten, A.] Univ Hosp Aachen, CPACC, Aachen, Germany., [Tacke, F.] Univ Hosp Aachen, DMIII, Aachen, Germany., [Marx, G.] Univ Hosp Aachen, OIC, Aachen, Germany., [Volkert, T.] Univ Hosp Muenster, Munster, Germany., [Schmutz, A.] Univ Med Ctr Freiburg, Fr
Published: 2019
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3. Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial

Author: Mazzinari G, Diaz-Cambronero O, Alonso-Iñigo JM, Garcia-Gregorio N, Ayas-Montero B, Ibañez JL, Serpa Neto A, Ball L, Gama de Abreu M, Pelosi P, Maupoey J, Argente Navarro MP, and Schultz MJ
Abstract: Transpulmonary driving pressure (ratio of tidal volume to respiratory system compliance) increases with increased intraabdominal pressure during laparoscopic surgery. High transpulmonary driving pressure during laparoscopic surgery is associated with increased risk of postoperative pulmonary complications.Intraoperative positive end-expiratory pressure prevents atelectasis, but may also cause overdistension.
Published: 2020

4. Effect of an individualized versus standard pneumoperitoneum pressure strategy on postoperative recovery: a randomized clinical trial in laparoscopic colorectal surgery

Author: Díaz-Cambronero O, Mazzinari G, Flor Lorente B, García Gregorio N, Robles-Hernandez D, Olmedilla Arnal LE, Martin de Pablos A, Schultz MJ, Errando CL, Argente Navarro MP, and on behalf of the IPPColLapSe II study investigators
Abstract: Background It remains uncertain whether individualization of pneumoperitoneum pressures during laparoscopic surgery improves postoperative recovery. This study compared an individualized pneumoperitoneum pressure (IPP) strategy with a standard pneumoperitoneum pressure (SPP) strategy with respect to postoperative recovery after laparoscopic colorectal surgery. Methods This was a multicentre RCT. The IPP strategy comprised modified patient positioning, deep neuromuscular blockade, and abdominal wall prestretching targeting the lowest intra-abdominal pressure (IAP) that maintained acceptable workspace. The SPP strategy comprised patient positioning according to the surgeon's preference, moderate neuromuscular blockade and a fixed IAP of 12 mmHg. The primary endpoint was physiological postoperative recovery, assessed by means of the Postoperative Quality of Recovery Scale. Secondary endpoints included recovery in other domains and overall recovery, the occurrence of intraoperative and postoperative complications, duration of hospital stay, and plasma markers of inflammation up to postoperative day 3. Results Of 166 patients, 85 received an IPP strategy and 81 an SPP strategy. The IPP strategy was associated with a higher probability of physiological recovery (odds ratio (OR) 2 center dot 77, 95 per cent c.i. 1 center dot 19 to 6 center dot 40, P = 0 center dot 017; risk ratio (RR) 1 center dot 82, 1 center dot 79 to 1 center dot 87, P = 0 center dot 049). The IPP strategy was also associated with a higher probability of emotional (P = 0 center dot 013) and overall (P = 0 center dot 011) recovery. Intraoperative adverse events were less frequent with the IPP strategy (P < 0 center dot 001) and the plasma neutrophil-lymphocyte ratio was lower (P = 0 center dot 029). Other endpoints were not affected. Conclusion In this cohort of patients undergoing laparoscopic colorectal surgery, an IPP strategy was associated with faster recovery, fewer intraoperative complications and less inflammation than an SPP strategy. Registration number: NCT02773173 ( ).
Published: 2020

5. A multifaceted individualized pneumoperitoneum strategy for laparoscopic colorectal surgery: a multicenter observational feasibility study

Author: Diaz-Cambronero O, Flor Lorente B, Mazzinari G, Vila Montañes M, García Gregorio N, Robles Hernandez D, Olmedilla Arnal LE, Argente Navarro MP, Schultz MJ, Errando CL, and IPPColLapSe study group
Subjects: Colorectal surgery, Colorectal surgery, Laparoscopy, Neuromuscular blockade, Laparoscopy, Neuromuscular blockade
Abstract: BackgroundWhile guidelines for laparoscopic abdominal surgery advise using the lowest possible intra-abdominal pressure, commonly a standard pressure is used. We evaluated the feasibility of a predefined multifaceted individualized pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure during laparoscopic colorectal surgery.MethodsMulticenter prospective study in patients scheduled for laparoscopic colorectal surgery. The strategy consisted of ventilation with low tidal volume, a modified lithotomy position, deep neuromuscular blockade, pre-stretching of the abdominal wall, and individualized intra-abdominal pressure titration; the effect was blindly evaluated by the surgeon. The primary endpoint was the proportion of surgical procedures completed at each individualized intra-abdominal pressure level. Secondary endpoints were the respiratory system driving pressure, and the estimated volume of insufflated CO2 gas needed to perform the surgical procedure.ResultsNinety-two patients were enrolled in the study. Fourteen cases were converted to open surgery for reasons not related to the strategy. The intervention was feasible in all patients and well-accepted by all surgeons. In 61 out of 78 patients (78%), surgery was performed and completed at the lowest possible IAP, 8mmHg. In 17 patients, IAP was raised up to 12mmHg. The relationship between IAP and driving pressure was almost linear. The mean estimated intra-abdominal CO2 volume at which surgery was performed was 3.2L.ConclusionA multifaceted individualized pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and resulted in an adequate working space in most patients at lower intra-abdominal pressure and lower respiratory driving pressure.ClinicalTrials.gov (Trial Identifier: NCT03000465).
Published: 2019

6. age: Observational data from the ICON audit

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Slavcovici, A, Bagin, V, Belsky, D, Palyutin, S, Shlyapnikov, S, Bikkulova, D, Gritsan, A, Natalia, G, Makarenko, E, Kokhno, V, Tolkach, A, Kokarev, E, Belotserkovskiy, B, Zolotukhin, K, Kulabukhov, V, Soskic, L, Palibrk, I, Jankovic, R, Jovanovic, B, Pandurovic, M, Bumbasirevic, V, Uljarevic, B, Surbatovic, M, Ladjevic, N, Slobodianiuk, G, Sobona, V, Cikova, A, Gebhardtova, A, Jun, C, Yunbo, S, Dong, U, Feng, S, Duan, M, Xu, Y, Xue, X, Gao, T, Xing, X, Zhao, X, Li, C, Gengxihua, G, Tan, H, Xu, J, Jiang, L, Tiehe, Q, Bingyu, Q, Shi, Q, Lv, Z, Zhang, L, Jingtao, L, Zhen, Z, Wang, Z, Wang, T, Yuhong, L, Zhai, Q, Chen, Y, Wang, C, Jiang, W, Ruilan, W, Xiaobo, H, Ge, H, Yan, T, Yuhui, C, Zhang, J, Jian-Hong, F, Zhu, H, Huo, F, Wang, Y, Zhuang, M, Ma, Z, Sun, J, Liuqingyue, L, Yang, M, Meng, J, Ma, S, Kang, Y, Yu, L, Peng, Q, Wei, Y, Zhang, W, Sun, R, Yeung, A, Wan, W, Sin, K, Lee, K, Wijanti, M, Widodo, U, Samsirun, H, Sugiman, T, Wisudarti, C, Maskoen, T, Hata, N, Kobe, Y, Nishida, O, 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Abstract: Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world. Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure. Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying. Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. All rights reserved. C1 [Kotfis, Katarzyna] Pomeranian Med Univ, Dept Anaesthesiol Intens Therapy & Acute Intoxica, Szczecin, Poland. [Wittebole, Xavier] UCL, Clin Univ St Luc, Dept Crit Care, Brussels, Belgium. [Jaschinski, Ulrich] Klinikum Augsburg, Klin Anasthesiol & Operat Intens Med, Augsburg, Germany. [Sole-Violan, Jordi] Hosp Univ Gran Canaria Dr Negrin, Dept Intens Care, Las Palmas Gran Canaria, Spain. [Kashyap, Rahul] Mayo Clin, Dept Anesthesia Ei Perioperat Med, Rochester, MN USA. [Leone, Marc] Aix Marseille Univ, Hop Nord, AP HM, Serv Anesthesie & Reanimat, Marseille, France. [Nanchal, Rahul] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Fontes, Luis E.] Hosp Alcides Carneiro, Petropolis Med Sch, Dept Intens Care & Evidence Based Med, Petropolis, Brazil. 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[Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA. [Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA. [Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA. [Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA. [Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA. [Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA. [Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA. [Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA. [Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia. [Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia. [Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia. [Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia. [Hawkins, D. J.] Joondalup Hlth Campus, Joondalup, WA, Australia. [Kilminster, M.] Lismore Base Hosp, Lismore, NSW, Australia. [Sturgess, D.] Mater Adult Hosp, South Brisbane, Qld, Australia. [Ziegenfuss, M.] Prince Charles Hosp, Brisbane, Qld, Australia. [O'Connor, S.] Royal Adelaide Hosp, Adelaide, SA, Australia. [Lipman, J.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Campbell, L.] Royal Darwin Hosp, Tiwi, NT, Australia. [Mcallister, R.] Royal Hobart Hosp, Hobart, Tas, Australia. [Roberts, B.] Sir Charles Gairdner Hosp, Nedlands, WA, Australia. [Williams, P.] Queen Elizabeth Hosp, Woodville, SA, Australia. [Parke, R.] Auckland Dist Hlth Board, Auckland, New Zealand. [Seigne, P.] Christchurch Hosp, Christchurch, New Zealand. [Freebairn, R.] Hawkes Bay Hosp, Hastings, New Zealand. [Nistor, D.] Palmerston North Hosp, Midcent Hlth, Palmerston North, New Zealand. [Oxley, C.] Middlemore Hosp, Auckland, New Zealand. [Young, P.] Wellington Hosp, Wellington, New Zealand. [Valentini, R.] Cemic, Buenos Aires, DF, Argentina. [Wainsztein, N.] Fleni, Buenos Aires, DF, Argentina. [Comignani, P.] Hosp Aleman, Buenos Aires, DF, Argentina. [Casaretto, M.] Hosp Cent San Isidro, Buenos Aires, DF, Argentina. [Sutton, G.] Hosp Fernandez, Buenos Aires, DF, Argentina. [Villegas, P.] Hosp Francisco Lopez Lima Area Programa Gen Roca, Gen Roca, Argentina. [Galletti, C.] Sanatorio Allende, Cordoba, Argentina. [Neira, J.] Sanatorio Trinidad Palermo, Buenos Aires, DF, Argentina. [Rovira, D.] Sanatorio Julio Corzo Rosario, Rosario, Santa Fe, Argentina. [Hidalgo, J.] Karl Heusner Mem Hosp, Belize City, Belize. [Hidalgo, J.] Belize Healthcare Partner, Belize City, Belize. [Sandi, F.] Hosp Obrero 1, La Paz, Bolivia. [Caser, E.] Cias Unimed Vitoria, Vitoria, ES, Brazil. [Thompson, M.] Evangelical Hosp Cachoeiro De Itapemirim, Cachoeiro De Itapemirim, Brazil. [D'agostino Dias, M.] Hosp 9 Julho, Sao Paulo, Brazil. [Fontes, L.] Hosp Alcides Carneiro, Petropolis, Brazil. [Lunardi, M.] Hosp Clin Luzia De Pinho Melo, Mogi Das Cruzes, Brazil. [Youssef, N.] Hosp Nacoes Curitiba, Curitiba, Parana, Brazil. [Lobo, S.] Hosp Base Famerp, Sao Jose Do Rio Preto, Brazil. [Silva, R.] Hosp Clin Niteroi, Niteroi, RJ, Brazil. [Sales Jr, J.] Hosp Clin Padre Miguel, Rio De Janeiro, Brazil. [Madeira Campos Melo, L.] Hosp Terapia Intens, Sao Paulo, Brazil. [Oliveira, M.] Hosp Trabalhador, Curitiba, Parana, Brazil. [Fonte, M.] Hosp Esperanza, Olinda, PE, Brazil. [Grion, C.] Hosp Evangel Londrina, Londrina, Brazil. [Feijo, C.] Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil. [Rezende, V] Hosp Geral Roraima, Boa Vista, Brazil. [Assuncao, M.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. [Neves, A.] Hosp Mater Dei, Belo Horizonte, MG, Brazil. [Gusman, P.; Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil. [Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil. [Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil. [Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil. [Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil. [Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil. [Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil. [Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil. [Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil. [Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil. [Houly, J.] Hosp Santapaula, Sao Paulo, Brazil. [Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil. [Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil. [Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil. [Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil. [Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil. [Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil. [Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil. [Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil. [Grion, C.] Hosp Univ Londrina, Londrina, Brazil. [Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil. [Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil. [Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil. [Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil. [Ugarte, S.] Clin Indisa, Providencia, Chile. [Tomicic, V] Clin Las Lilas, Providencia, Chile. [Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile. [Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile. [Escamilla, I] Hosp El Pino, San Bernardo, Chile. [Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile. [Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia. [Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia. [Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia. [Benitez, F.] Clin La Estancia SA, Popayan, Colombia. [Guerra Urrego, A.] Clin Medellin, Medellin, Colombia. [Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia. [Ortiz, G.] Hosp Santa Clara, Bogota, Colombia. [Villalba Gaviria, M.] Hosp Univ Fdn Santa Fe De Bogota, Bogota, Colombia. [Salas, D.] Calderon Guardia Hosp, San Jose, Costa Rica. [Ramirez-Arce, J.] Hosp Dr Rafael Angel Varlderon Guardia Ccss, San Jose, Costa Rica. [Salgado, E.] Clin La Merced, Quito, Ecuador. [Morocho, D.] Hosp Eugenio Espejo, Quito, Ecuador. [Vergara, J.] Hosp Luis Vernaza, Quito, Ecuador. [Chung Sang, M.] Shdug Sistema Hosp Docente De La Univ Guayaquil, Quito, Ecuador. [Orellana-Jimenez, C.] Gen Hosp, San Salvador, El Salvador. [Garrido, L.] Hosp Ctr Med, Guatemala City, Guatemala. [Diaz, O.] Inst Hondureno Seguro Social, La Ceiba, Honduras. [Resiere, D.] Ctr Hosp Univ Ft De France, Fort De France, Martinique, France. [Osorio, C.] Ctr Estatal Cuidados Crit, Salamanca, Mexico. [De La Vega, A.] Ctr Med Nacl 20 Noviembre Issste, Mexico City, DF, Mexico. [Carrillo, R.] Fdn Clin Med Sur, Mexico City, DF, Mexico. [Sanchez, V] Hosp San Jose TEC Monterrey, Monterrey, Mexico. [Villagomez, A.] Hosp 1 Octubre, Issste, Mexico. [Martinez Zubieta, R.] Hosp Espanol Mexico, Mexico City, DF, Mexico. [Sandia, M.] Hosp Gen Ajusco Medio, Mexico City, DF, Mexico. [Zalatiel, M.] Hosp Gen Guadalupe Victoria, Texcoco, Mexico. [Poblano, M.] Hosp Juarez Mexico, Mexico City, DF, Mexico. [Rodriguez Gonzalez, D.] Hosp Civil Guadalajara, Hspitaljuan I Menchaca, Guadalajara, Jalisco, Mexico. [Arrazola, F.; Juan Francisco, L.] Inst Mexicano Seguro Social, Mexico City, DF, Mexico. [Liamendys-Silva, S. A.] Inst Nacl Cancerol, Mexico City, DF, Mexico. [Hernandez, M.] ISSSTE Guerra Moya, Mexico City, DF, Mexico. [Hernandez, M.] Med Ctr ISSEMYM Toluca, Mexico City, DF, Mexico. [Rodriguez Cadena, D.] Mixta, Mexico City, DF, Mexico. [Lopez Islas, I.] Secretaria Salud Dist Fed, Mexico City, DF, Mexico. [Ballesteros Zarzavilla, C.] Hosp Santo Comas, Panama City, Panama. [Matos, A.] Social Secur Hosp, La Chorrera, Panama. [Oyanguren, I] Clin Anglo Amer, Lima, Peru. [Cerna, J.] Essalud, Lima, Peru. [Quispe Sierra, R.] Hosp Nacl Dos De Mayo, Lima, Peru. [Jimenez, R.] Hosp Rebagliati, Lince Dist, Peru. [Castillo, L.] Inst Nacl Enfermedades Neoplas, Surquillo, Peru. [Ocal, R.] Gulhane Med Fac, Istanbul, Turkey. [Sencan, A.] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey. [Gianoni, S. Mareque] CAMS, Montevideo, Uruguay. [Deicas, A.] CASMU, Montevideo, Uruguay. [Hurtado, J.] Hosp Espanol Asse, Montevideo, Uruguay. [Burghi, G.] Hosp Maciel, Montevideo, Uruguay. [Martinelli, A.] Ctr Med Caracas, Caracas, Venezuela. [Von der Osten, I] Hosp Miguel Perez Carreno, Caracas, Venezuela. [Du Maine, C.] MSF Trauma Hosp Kunduz, Kunduz, Afghanistan. [Bhattacharyya, M.] Amri Hosp, Kolkata, India. [Bandyopadhyay, S.] Amri Hosp Salt Lake, Kolkata, W Bengal, India. [Yanamala, S.] Apollo Hosp, Hyderabad, India. [Gopal, P.] Apollo Hosp, Bangalore, Karnataka, India. [Sahu, S.] Apollo Hosp, Bhubaneswar, India. [Ibrahim, M.] Apollo Special Hosp, Chennai, Tamil Nadu, India. [Rathod, D.] Asian Heart Inst, Mumbai, Maharashtra, India. [Mukundan, N.] Baby Mem Hosp Ltd, Calicut, Kerala, India. [Dewan, A.] Batra Hosp & Mrc, New Delhi 110062, India. [Amin, P.] Bombay Hosp Inst Med Sci, Mumbai, Maharashtra, India. [Samavedam, S.] Care Hosp, Hyderabad, India. [Shah, B.] Cims Hosp, Ahmadabad, Gujarat, India. [Gurupal, D.] Columbiaasia Hosp, Mysore, Karnataka, India. [Lahkar, B.] Dispur Hosp, Gauhati, India. [Mandal, A.] Fortis Hosp, Bangalore, Karnataka, India. [Sircar, M.] Fortis Hosp, Noida, India. [Ghosh, S.] Fortis Escorts Hosp, Faridabad, India. [Balasubramani, V] Ganga Med Ctr & Hosp P Ltd, Coimbatore, Tamil Nadu, India. [Kapadia, F.] Hinduja Hosp, Mumbai, Maharashtra, India. [Vadi, S.] KDAH, Mumbai, Maharashtra, India. [Nair, K.] Kerala Inst Med Sci, RMCC, Thiruvananthapuram, Kerala, India. [Tripathy, S.] Kalinga Inst Med Sci, DTEM, Bhubaneswar, Odisha, India. [Nandakumar, S.] Kovai Med Ctr & Hosp, Coimbatore, Tamil Nadu, India. [Sharma, J.] Medanta Medic, Gurgaon, India. [Kar, A.] Med Superspecialty Hosp, Kolkata, W Bengal, India. [Jha, S.] Metro Heart Inst Multispecial, Faridabad, India. [Gurav, K. Zirpe] Ruby Hall Pune, Pune, Maharashtra, India. [Patel, M.] Saifee Hosp, Mumbai, Maharashtra, India. [Bhaysar, A.] Spandan Multispecial Hosp, Vadodara, India. [Samaddar, D.] Tata Main Hosp, Jamshedpur, Jharkhand, India. [Kulkarni, A.] Tata Mem Hosp, Mumbai, Maharashtra, India. [Hashmi, M.] Aga Khan Univ, Karachi, Pakistan. [Ali, W.] Hearts Int Hosp, Rawalpindi, Pakistan. [Nadeem, S.] Liaquat Natl Hosp, Karachi, Pakistan. [Indraratna, K.] Sri Jayewardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka. [Margarit, A.] Hosp Nostra Senyora Meritxell, Les Escaldes, Andorra. [Urbanek, P.] Akh Wien, Vienna, Austria. [Schlieber, J.] Allgemeines & Orthopad Landeskrankenhaus Stolzalp, Stolzalpe, Austria. [Reisinger, J.] Barmherzige Schwestern Linz, Linz, Austria. [Auer, U.] Gen Hosp Braunau, Braunau, Austria. [Hartjes, A.] Krankenhaus D Barmherzigen Schwestern Ried II, Ried Im Innkreis, Austria. [Lerche, A.] Krankenhaus Floridsdorf, Vienna, Austria. [Janous, T.] LK Gmund Waidhofen Thaya Zwettl, Standort Zwettl, Austria. [Kink, E.] LKH Horgas Enzenbach, Gratwein, Austria. [Krahulec, W.] LKH West, Graz, Austria. [Smolle, K.] Univ Hosp, Graz, Austria. [Van der Schueren, M.] AZ Groeninge Kortrijk, Kortrijk, Belgium. [Thibo, P.] AZ Jan Palfijn Gent, Ghent, Belgium. [Vanhoof, M.] AZ Turnhout, Turnhout, Belgium. [Ahmet, I] Bracops Anderlecht, Anderlecht, Belgium. [Gadisseux, P.] Ctr Hosp Mouscron, Mouscron, Belgium. [Dufaye, P.] CH Peltzer La Tourelle, Verviers, Belgium. [Jacobs, O.] Chirec Edith Cavell, Auderghem, Belgium. [Fraipont, V] CHR Citadelle, Liege, Belgium. [Biston, P.] CHU Charleroi, Charleroi, Belgium. [Dive, A.] CHU Mt Godinne, Yvoir, Belgium. [Bouckaert, Y.] CHU Tivoli, La Louviere, Belgium. [Gilbert, E.] CHwapi, Tournai, Belgium. [Gressens, B.] Clin St Pierre Ottignies, Ottignies, Belgium. [Pinck, E.] Clin Maternite St Elisabeth, Namur, Belgium. [Collin, V] Clin Europe St Michel, Etterbeek, Belgium. [Vincent, J. L.] Erasme Univ Hosp, Anderlecht, Belgium. [De Waele, J.] Ghent Univ Hosp, Ghent, Belgium. [Rimachi, R.] Moliere Hosp, Forest, Belgium. [Gusu, D.] Notre Dame, Brussels, Belgium. [De Decker, K.] Onze Lieve Vrouw Hosp, Aalst, Belgium. [Mandianga, K.] Ixelles Hosp, Ixelles, Belgium. [Heytens, L.] Sint Augustinus, Antwerp, Belgium. [Wittebole, X.] St Luc Univ Hosp UCL, Brussels, Belgium. [Spapen, H.] UZ Brussel, Brussels, Belgium. [Olivier, V] Vivalia Site Libramt, Libramont, Belgium. [Vandenheede, W.] VZW Gezondheidszorg Oostkust Knokke Heist, Knokke Heist, Belgium. [Rogiers, P.] ZNA Middelheim, Antwerp, Belgium. [Kolodzeike, P.] Herning Hosp, Herning, Denmark. [Kruse, M.] Hjoerring Hosp, Hjorring, Denmark. [Andersen, T.] Vejle Hosp, Vejle, Denmark. [Harjola, V] Helsinki Univ Cent Hosp, Helsinki, Finland. [Saarinen, K.] Seinajoki Cent Hosp, Seinajoki, Finland. [Leone, M.] Aix Marseille Univ, Hop Nord, Marseille, France. [Durocher, A.] Calmette Hosp, Lille, France. [Moulront, S.] Ctr Hosp Dunkerque, Dunkerque, France. [Lepape, A.] Ctr Hosp Lyon Sud, Lyon, France. [Losser, M.] CHU Nancy Brabois, Nancy, France. [Cabaret, P.] CH St Philibert, GHICL, Lille, France. [Kalaitzis, E.] CHR Dax, Dax, France. [Zogheib, E.] CHU Amiens, Amiens, France. [Charve, P.] CHU Dijon, Dijon, France. [Francois, B.] CHU Dupuytren, Limoges, France. [Lefrant, J. Y.] CHU Nimes, Nimes, France. [Beilouny, B.] Ctr Hosp Troyes, Troyes, France. [Forceville, X.] Ctr Hosp Meaux, Grp Hosp Est Francilien, Meaux, France. [Misset, B.] Grp Hosp Paris St Joseph, Paris, France. [Jacobs, F.] Hop Antoine Beclere, Clamart, France. [Floccard, B.] Hop Edouard Herriot, Lyon, France. [Payen, D.] Hop Lariboisere, AP HP, Paris, France. [Wynckel, A.] Hop Maison Blanche, Reims, France. [Castelain, V] Hop Univ Strasbourg, Strasbourg, France. [Faure, A.] Hosp Civils Lyon, Lyon, France. [Lavagne, P.] CHU Grenoble, Grenoble, France. [Thierry, I] CHU Nantes, Nantes, France. [Moussa, M.] CHRU Lille, Reanimat Chirurg Cardiovasc, Lille, France. [Vieillard-Baron, A.] Univ Hosp Ambroise Pare, Boulogne, France. [Durand, M.] Univ Hosp Grenoble, La Tronche, France. [Gainnier, M.] Univ Hosp Marseille, Marseille, France. [Ichai, C.] Univ Nice, Nice, France. [Arens, S.] Alexianer Krefeld Gmbh, Krefeld, Germany. [Hoffmann, C.] Charite Hochschulmed Berlin, Berlin, Germany. [Kaffarnik, M.] Charite, Berlin, Germany. [Scharnofske, C.] Diakoniekrankenhaus Henriettenstiftung Gmbh, Hannover, Germany. [Voigt, I] Elisabeth Krankenhaus Essen, Essen, Germany. [Peckelsen, C.] Munich Municipal Hosp Grp, Harlaching Hosp, Munich, Germany. [Weber, M.] Helios St Johannes Klin, Duisburg, Germany. [Gille, J.] Hosp St Georg Leipzig, Leipzig, Germany. [Lange, A.] Klin Hennigsdorf Oberhavel Kliniken Gmbh, Hennigsdorf, Germany. [Schoser, G.] Klin Tettnang, Tettnang, Germany. [Sablotzki, A.] Klinikum St Georg Leipzig, Leipzig, Germany. [Jaschinski, U.; Bluethgen, A.] Klinikum Augsburg, Augsburg, Germany. [Vogel, F.] Klinikum Bremen Mitte, Bremen, Germany. [Tscheu, A.] Klinikum Bremen Ost, Bremen, Germany. [Fuchs, T.] Klinikum Heidenheim, Heidenheim, Germany. [Wattenberg, M.] Klinikum Links Weser Gmbh, Bremen, Germany. [Helmes, T.] Klinikum Luedenscheid, Luedenscheid, Germany. [Scieszka, S.] Krankenhaus Neuwerk, Monchengladbach, Germany. [Heintz, M.] Marienkrankenhaus Schwerte, Schwerte, Germany. [Sakka, S.] Med Ctr Cologne Merheim, Cologne, Germany. [Kohler, J.] Schwarzwald Baar Klinikum Villingen Schwenningen, Villingen Schwenningen, Germany. [Fiedler, F.] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany. [Danz, M.] St Martinus Hosp Olpe, Olpe, Germany. [Sakr, Y.] Uniklinikum Jena, Jena, Germany. [Riessen, R.] Univ Klinikum Tubingen, Tubingen, Germany. [Kerz, T.] Univ Med Mainz, Mainz, Germany. [Kersten, A.] Univ Hosp Aachen, CPACC, Aachen, Germany. [Tacke, F.] Univ Hosp Aachen, DMIII, Aachen, Germany. [Marx, G.] Univ Hosp Aachen, OIC, Aachen, Germany. [Volkert, T.] Univ Hosp Muenster, Munster, Germany. [Schmutz, A.] Univ Med Ctr Freiburg, Freiburg, Germany. [Nierhaus, A.; Kluge, S.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Abel, P.] Univ Med Greifswald, Greifswald, Germany. [Janosi, R.] Univ Duisburg Essen, Essen, Germany. [Utzolino, S.] Univ Freiburg, Freiburg, Germany. [Bracht, H.] Univ Clin Ulm, Ulm, Germany. [Toussaint, S.] Vivantes Klinikum Neukoelln, Berlin, Germany. [Peftoulidou, M. Giannakou] Ahepa Univ Hosp, Thessaloniki, Greece. [Myrianthefs, P.] Univ Athens, Athens, Greece. [Armaganidis, A.] Univ Athens, Med Sch, Athens, Greece. [Routsi, C.] Evangelismos Med Ctr, Athens, Greece. [Xini, A.] Gen Hosp Chania, Iraklion, Greece. [Mouloudi, E.] Hippokrateion Hosp, Thessaloniki, Greece. [Kokoris, I] Gen Hosp Velos, Volos, Greece. [Kyriazopoulos, G.] Lamia Gen Hosp, Lamia, Greece. [Vlachos, S.] Naval & Vet Hosp, Athens, Greece. [Lavrentieva, A.] Apanikolaou Gen Hosp, Thessaloniki, Greece. [Partala, P.] Univ Hosp Alexandroupolis, Alexandroupolis, Greece. [Nakos, G.] Univ Ioannina, Ioannina, Greece. [Moller, A.] Landspitali Univ Hosp, Reykjavik, Iceland. [Stefansson, S.] Landspitali Univ Hosp Fossvogur, Reykjavik, Iceland. [Barry, J.] Cork Univ Hosp, Cork, Ireland. [O'Leary, R.] Mercy Univ Hosp, Cork, Ireland. [Motherway, C.] Mid Western Reg Hosp Complex, Limerick, Ireland. [Faheem, M.] Midland Reg Hosp Mullingar, Mullingar, Co Westmeath, Ireland. [Dunne, E.] St Vincents Univ Hosp, Dublin, Ireland. [Donnelly, M.] Tallaght Hosp, Dublin, Ireland. [Konrad, T.] Univ Hosp Galway, Galway, Ireland. [Bonora, E.] Anesthesiol & Intens Care, Milan, Italy. [Achilli, C.] AO Osped Niguarda Ca Granda, Milan, Italy. [Rossi, S.] Azienda Osped Padova, Padua, Italy. [Castiglione, G.] Azienda Ospedaliero Univ Policlin Vittorio Emanue, Catania, Italy. [Penis, A.] Careggi Teaching Hosp, Florence, Italy. [Albanese, D.] Clinicized Hosp Ss Annunziata Chieti, Chieti, Italy. [Stocchetti, N.] Fdn Irccs Ca Granda Osped Maggiore Policlin, Milan, Italy. [Stocchetti, N.] Univ Milan, Milan, Italy. [Citerio, G.] H San Gerardo Monza, Monza, Italy. [Mozzoni, L.] Icu Ceccarini Hosp Ricc, Rimini, Italy. [Sisillo, E.] Irccs Ctr Cardiol Monzino, Milan, Italy. [De Negri, P.] Irccs Ctr Riferimento Oncol Basilicata, Basilicata, Italy. [Savioli, M.] Irccs Fdn Ca Granda, Osped Maggiore Policlin, Milan, Italy. [Vecchiarelli, P.] Osped Belcolle Viterbo, Viterbo, Italy. [Puflea, F.; Stankovic, V] Osped Civile Maggiore AOUI Verona, Verona, Italy. [Minoja, G.] Osped Circolo E Fdn Macchi, Varese, Italy. [Montibeller, S.] Osped Trento, Azienda Prov I Servizi Sanitari Prov Autonoma Tre, Trento, Italy. [Calligaro, P.] Osped Orlandi, Bussolengo, Italy. [Sorrentino, R.] Osped Regionale U Parini Aosta, Aosta, Italy. [Feri, M.] Osped San Donato Arezzo, Arezzo, Italy. [Zambon, M.] Osped San Raffaele, Segrate, Italy. [Colombaroli, E.] Policlin GB Rossi AOUI Verona, Verona, Italy. [Giarratano, A.] Policlin Univ Palermo, Palermo, Italy. [Pellis, T.] Santa Maria Angeli Hosp, Rome, Italy. [Capra, C.] Saronno Hosp, Saronno, Italy. [Antonelli, M.] Univ Cattolica Sacro Cuore, Milan, Italy. [Gullo, A.] Univ Catania, Catania, Italy. [Chelazzi, C.] Univ Florence, Florence, Italy. [De Capraris, A.] Univ Foggia, Foggia, Italy. [Patroniti, N.] Univ Milano Bicocca, San Gerardo Hosp, Milan, Italy. [Girardis, M.] Univ Modena, Modena, Italy. [Franchi, F.] Univ Siena, Siena, Italy. [Berlot, G.] Univ Trieste, Trieste, Italy. [Buttigieg, M.] Mater Hosp, Msida, Malta. [Ponssen, H.] Albert Schweitzer Hosp, Dordrecht, Netherlands. [Cate, J. Ten] Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, Netherlands. [Bormans, L.] Atrium Med Ctr Parkstad, Heerlen, Netherlands. [Husada, S.] Bovenij Hosp, Amsterdam, Netherlands. [Buise, M.] Catharina Hosp, Eindhoven, Netherlands. [Van Der Hoven, B.] Erasmus MC, Rotterdam, Netherlands. [Reidinga, A.] Martiniziekenhuis Groningen, Groningen, Netherlands. [Kuiper, M.] Med Ctr Leeuwarden, Leeuwarden, Netherlands. [Pickkers, P.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Kluge, G.] Slotervaart Ziekenhuis Amsterdam, Amsterdam, Netherlands. [Den Boer, S.] Spaarne Ziekenhuis, Hoofddrop, Netherlands. [Kesecioglu, J.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Van Leeuwen, H.] Ziekenhuis Rijnstate, Arnhem, Netherlands. [Flaatten, H.] Haukeland Hosp, Bergen, Norway. [Mo, S.] Trondheim Reg & Univ Hosp, St Olays Hosp, Trondheim, Norway. [Branco, V] Ctr Hosp Cova Da Beira, Covilha, Portugal. [Rua, F.] Ctr Hosp Porto, Porto, Portugal. [Lafuente, E.] Ctr Hosp Tamega E Sousa, Guilhufe, Portugal. [Sousa, M.] Ctr Hosp Gaia Espinho, Epe, Espinho, Portugal. [Catorze, N.] Ctr Hosp Medio Tejo, Lisbon, Portugal. [Barros, M.] Ctr Hosp Tondela Viseu, Viseu, Portugal. [Pereira, L.] Faro Hosp, Faro, Portugal. [De Oliveira, A. Vintern] Hosp Curry Cabral, Lisbon, Portugal. [Gomes, J.] Hosp Luz, Lisbon, Portugal. [Gaspar, I] Hosp Egas Moniz Chlo, Lisbon, Portugal. [Pereira, M.] Ctr Hosp Porto, Hosp Santo Antonio, Proto, Portugal. [Cymbron, M.] Hosp Divino Espirito Santo, Epe, Ponta Delgada, Portugal. [Dias, A.] Hosp Espirito Santo Evora Epe, Evora, Portugal. [Almeida, E.] Hosp Garcia Orta, Almada, Portugal. [Beirao, S.] Hosp Geral Ctr Hosp E Univ Coimbra, Coimbra, Portugal. [Serra, I] Hosp Prof Doutor Fernando Fonseca Epe, Amadora, Portugal. [Ribeiro, R.] Hosp Sao Bernardo, Setubal, Portugal. [Povoa, P.] Hosp Sao Francisco Xavier, Chlo, Lisbon, Portugal. [Faria, F.] Inst Portugues Oncol Francisco Gentil, Porto, Portugal. [Costa-E-Silva, Z.] Santa Maria Hosp, Lisbon, Portugal. [Nobrega, A.] Serv Saude Regiao Autonoma Madeira, Funchal, Portugal. [Fernandes, F.] UCIP, Lisbon, Portugal. [Gabriel, J.] ULS Castelo Branco, Castelo Branco, Portugal. [Voga, G.] Gen Hosp Celje, Celje, Slovenia. [Rupnik, E.] Gen Hosp Izola, Izola, Slovenia. [Kosec, L.] Gen Hosp Novo Mesto, Novo Mesto, Slovenia. [Povsic, M. Kerin] Oncol Inst, Ljubljana, Slovenia. [Osojnik, I] Ukc Maribor, Maribor, Slovenia. [Tomic, V] Univ Clin Resp & Allerg Dis, Golnik, Slovenia. [Sinkovic, A.] Univ Clin Ctr Maribor, Maribor, Slovenia. [Gonzalez, J.] CH Salamanca, Salamanca, Spain. [Zavala, E.] Clin Hosp, Barcelona, Spain. [Perez Valenzuela, A.] Complejo Hosp Jaen, Jaen, Spain. [Marina, L.] Complejo Hosp Toledo, Toledo, Spain. [Vidal-Cortes, P.] Complexo Hosp Univ Ourense, Orense, Spain. [Posada, I] Complexo Hosp Univ Vigo, Galicia, Spain. [Ignacio Martin-Loeches, A.] Corp Sanitaria Parc Tauli, Barcelona, Spain. [Munoz Guillen, N.] Cruz Roja Hosp, Seville, Spain. [Palomar, M.] H Vall Hebron, Barcelona, Spain. [Sole-Violan, U.] HGGC Dr Negrin, Madrid, Spain. [Torres, A.] Hosp Clin Barcelona, Barcelona, Spain. [Gonzalez Gallego, M.] Hosp Clin San Carlos, Madrid, Spain. [Aguilar, G.] Hosp Clin Univ Valencia, Valencia, Spain. [Montoiro Allue, R.] Hosp Clin Univ Lozano Blesa, Zaragoza, Spain. [Argueso, M.] Hosp Clin Valencia, Valencia, Spain. [Parejo, M.] Hosp La Ribera, Valencia, Spain. [Palomo Navarro, M.] Hosp Sagunto, Port De Sagunt, Spain. [Jose, A.] Hosp San Juan Alicante, Alicante, Spain. [Nin, N.] Hosp Torrejon de Ardoz, Madrid, Spain. [Alvarez Lerma, F.] Hosp Mar, Barcelona, Spain. [Martinez, O.] Hosp Tajo, Madrid, Spain. [Tenza Lozano, E.] Hosp Gen Univ Elche, Elche, Spain. [Arenal Lopez, S.; Perez Granda, M.] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Moreno, S.] Hosp Gen Univ Santa Lucia, Murcia, Spain. [Llubia, C.] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain. [De la Fuente Martos, C.] Hosp Infanta Margarita, Cabra, Spain. [Gonzalez-Arenas, P.] Hosp Infanta Sofia, Madrid, Spain. [Llamas Fernandez, N.; Gil Rueda, B.] Hosp JM Morales Meseguer, Murcia, Spain. [Estruch Pons, I] Hosp Marina Salu Denia Alicante, Alicante, Spain. [Cruza, N.] Hosp Nuestra Senora Prado, Toledo, Spain. [Maroto, F.] Hosp San Juan De Dios Aljarafe, Bormujos, Spain. [Estella, A.] Hosp Sas Jerez, Andalucia, Spain. [Ferrer, A.] Hosp Son Llatzer, Palma De Mallorca, Spain. [Iglesias Fraile, L.; Quindos, B.] Hosp Univ Cent Asturias, Oviedo, Spain. [Quintano, A.] Hosp Univ Alava, Santiago, Spain. [Tebar, M.] Hosp Univ Basurto, Bilbao, Spain. [Cardinal, I] Hosp Univ Getafe, Getafe, Spain. [Reyes, A.] Hosp Univ La Princesa, Madrid, Spain. [Rodriguez, A.] Hosp Univ Tarragona Joan Xxiii, Tarragona, Spain. [Abella, A.] Hosp Univ Henares, Coslada, Spain. [Garcia Del Valle, S.] Hosp Univ Fdn Alcorcon, Alcorcon, Spain. [Yus, S.; Maseda, E.] Hosp Univ La Paz, Madrid, Spain. [Berezo, U.] Hosp Univ Rio Hortega, Valladolid, Spain. [Tejero Pedregosa, A.] Hosp Univ San Cecilio, Granada, Spain. [Laplaza, C.] Hosp Virgen Del Camino, Pamplona, Spain. [Ferrer, R.] Mutua Terrassa Univ Hosp, Terrassa, Spain. [Rico-Feijoo, U.] Rao Hortega Univ Hosp, Valladolid, Spain. [Rodriguez, M.] Serv Andaluz Salud, Andalucia, Spain. [Monedero, P.] Univ Okalingaf Navarra, Navarra, Spain. [Eriksson, K.] Karolinska Univ Hosp, Solna, Sweden. [Eriksson, K.] Karolinska Inst, Solna, Sweden. [Lind, D.] Sunderby Hosp, Lulea, Sweden. [Chabanel, D.] Hop Intercantonal La Broye, Payerne, Switzerland. [Zender, H.] Hop Neuchatelois La Chaux De Fonds, La Chaux De Fonds, Switzerland. [Heer, K.] Lindenhofspital, Bern, Switzerland. [Frankenberger, B.] Regionalspital Surselva Ilanz, Ilanz, Switzerland. [Jakob, S.] Univ Hosp Bern, Bern, Switzerland. [Mathew, S.] Alexandra Hosp Redditch, Redditch, England. [Downes, R.] Blackpool Teaching Hosp, Blackpool, England. [Groba, C. Barrera] Brighton & Sussex Univ Hosp, Brighton, E Sussex, England. [Johnston, A.] Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England. [Meacher, R.] Charing Cross Hosp, London, England. [Keays, R.] Chelsea & Westminster Hosp, London, England. [Haji-Michael, P.] Christie Fdn Trust, Manchester, Lancs, England. [Tyler, C.] Cty Hosp, Lincoln, England. [Ferguson, A.] Craigavon Area Hosp, Craigavon, North Ireland. [Jones, S.] Cumberland Infirm, Carlisle, England. [Tyl, D.] Darent Valley Hosp, Dartford, England. [Ball, A.] Dorset Cty Hosp, Dorchester, England. [Vogel, U.] Ealing Hosp NHS Trust, Southall, Middx, England. [Booth, M.] Glasgow Royal Infirm, Glasgow, Lanark, Scotland. [Downie, P.] Gloucester Royal Hosp, Gloucester, England. [Watters, M.] Great Western Hosp, Swindon, Wilts, England. [Brett, S.] Imperial Coll Healthcare NHS Trust, London, England. [Garfield, M.] Ipswich Hosp Nhs Trust, Ipswich, Suffolk, England. [Everett, L.] James Paget Univ Hosp NHS Fdn Trust, Great Yarmouth, Norfolk, England. [Heenen, S.] Kings Coll Hosp London, London, England. [Dhir, S.] Kings Mill Hosp, Sutton In Ashfield, England. [Beardow, Z.] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Mostert, M.] Lewisham Healthcare NHS Trust, London, England. [Brosnan, S.] Luton & Dunstable Hosp NHS Trust, Luton, Beds, England. [Pinto, N.] Medway Maritime Hosp, Gillingham, England. [Harris, S.] Musgrove Pk Hosp, Taunton, Somerset, England. [Summors, A.] Nevill Hall Hosp, Abergavenny, Wales. [Andrew, N.] Pilgrim Hosp, Boston, England. [Rose, A.] Mid Yorkshire NHS Trust, Pinderfields Hosp, Wakefield, England. [Appelboam, R.] Plymouth Hosp Nhs Trust, Plymouth, Devon, England. [Davies, O.] Princess Royal Hosp Telford, Telford, Shrops, England. [Vickers, E.] Royal Bournemouth Hosp, Bournemouth, Dorset, England. [Agarwal, B.] Royal Free Hampstead NHS Fdn Trust, London, England. [Szakmany, T.] Royal Glamorgan Hosp, Llantrisant, Wales. [Wimbush, S.] Royal Hampshire Cty Hosp, Winchester, Hants, England. [Welters, I] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Pearse, R.] Barts Hlth NHS Trust, Royal London Hosp, London, England. [Hollands, R.] Royal Shrewsbury Hosp, Shrewsbury, Salop, England. [Kirk-Bayley, U.] Royal Surrey Cty Hosp, Guildford, Surrey, England. [Fletcher, N.] St Georges Healthcare, London, England. [Bray, B.] Surrey & Sussex Healthcare Trust, Redhill, Surrey, England. [Brealey, D.] Univ Coll Hosp, London, England.
Published: 2019

7. CRISPR-Cas systems: ushering in the new genome editing era

Author: Rojo, FP, Nyman, RKM, Johnson, AAT, Navarro, MP, Ryan, MH, Erskine, W, Kaur, P, Rojo, FP, Nyman, RKM, Johnson, AAT, Navarro, MP, Ryan, MH, Erskine, W, and Kaur, P
Abstract: In recent years there has been great progress with the implementation and utilization of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) systems in the world of genetic engineering. Many forms of CRISPR-Cas9 have been developed as genome editing tools and techniques and, most recently, several non-genome editing CRISPR-Cas systems have emerged. Most of the CRISPR-Cas systems have been classified as either Class I or Class II and are further divided among several subtypes within each class. Research teams and companies are currently in dispute over patents for these CRISPR-Cas systems as numerous powerful applications are concurrently under development. This mini review summarizes the appearance of CRISPR-Cas systems with a focus on the predominant CRISPR-Cas9 system as well as the classifications and subtypes for CRISPR-Cas. Non-genome editing uses of CRISPR-Cas are also highlighted and a brief overview of the commercialization of CRISPR is provided.
Published: 2018

8. Degradation, release and bioavailability of 14C DDT and 14C DDE sediment residues to oysters and mussels

Author: Navarro Mp and Bajet Cm
Subjects: Oyster, Geologic Sediments, Insecticides, animal structures, Dichlorodiphenyl Dichloroethylene, Biological Availability, DDT, biology.animal, parasitic diseases, Environmental Chemistry, Animals, Tissue Distribution, Carbon Radioisotopes, Waste Management and Disposal, Water Science and Technology, biology, Brackish water, Chemistry, organic chemicals, fungi, Hard water, Sediment, Biota, General Medicine, Mussel, Pesticide, Ostreidae, Bivalvia, Environmental chemistry, Seawater, Adsorption, geographic locations, Water Pollutants, Chemical
Abstract: Sediment borne pesticides are one of the major routes of transport of pesticides into the aquatic environment and could affect biota living closely in contact with it. Sediment residues of DDT were found to be easily adsorbed (95.0%) and were released in hard water (8.4%) and seawater (0.1%). DDT and DDE sediment residues were released into sterile and nonsterile brackish water indicating minimal role of micro-organisms. DDT was detected in oyster and in mussel with an average of 46-62% in the shell, 19-31% in the tissues and 19-23% in the fluids. Most of the sediment residues were extractable and released residues in water were in the form of DDT. In the presence oysters, bound was transformed into extractable DDT in sediment after 30 days equivalent to 26% of the total concentration. Most biota residues were extractable and an average of 46% was transformed to DDE. Uptake of residues depend on whether the source of contamination was by direct addition to the water or through sediment residues, if food was given or not, if the source of sediment residues were either aged or freshly treated and if residues were extractable or non-extractable.
Published: 2002

9. Iron metabolism in rats fed diets containing heated glucose-lysine

Author: Cristina Delgado-Andrade, Seiquer, I., Valverde, A., Navarro, Mp, and Comisión Interministerial de Ciencia y Tecnología, CICYT (España)
Abstract: Trabajo presentado al Conjoint congress SENC/NS, celebrado en Pamplona (España) del 8 al 11 de septiembre de 1999., Supported by CICYT.
Published: 1999

10. High triglyceride levels as a predictor of mortality in AIDS patients

Author: Zamora L, Vilardell E, González-Clemente Jm, Miró Jm, and Navarro Mp
Subjects: Adult, Hypertriglyceridemia, Male, medicine.medical_specialty, Aids patients, Acquired Immunodeficiency Syndrome, Triglyceride, business.industry, Immunology, Survival Analysis, chemistry.chemical_compound, Infectious Diseases, chemistry, Internal medicine, medicine, Immunology and Allergy, Humans, business, Follow-Up Studies, Retrospective Studies
Published: 1993

11. Relationship between moderate food restriction during pregnancy and Fe, Zn and Cu contents in maternal tissues and foetuses

Author: Vaquero, MP, primary and Navarro, MP, additional
Published: 1996
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12. Influence of moderate food restriction on calcium metabolism in pregnant rats

Author: Vaquero, MP, primary and Navarro, MP, additional
Published: 1993
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13. Influence of Ethanol on Nutrients Utilization

Author: G. Varela, M. M. Andújar, and Navarro Mp
Subjects: chemistry.chemical_compound, Ethanol, Nutrient, Chemistry, Food science
Published: 1981
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14. Biocontrol Activity of Bacillus altitudinis CH05 and Bacillus tropicus CH13 Isolated from Capsicum annuum L. Seeds against Fungal Strains.

Author: Espinosa Bernal MA, Mena Navarro MP, Arvizu Gómez JL, Saldaña C, Ramos López MÁ, Amaro Reyes A, Escamilla García M, Pacheco Aguilar JR, Moreno VP, Rodríguez Morales JA, Álvarez Hidalgo E, Nuñez Ramírez J, Hernández Flores JL, and Campos Guillén J
Abstract: In this study, seed-surface-associated bacteria from fresh fruits of Capsicum spp. were analyzed to explore potential isolates for biocontrol of phytopathogenic fungal strains. A total of 76 bacterial isolates were obtained from three different species of chili pepper ( C. annuum L., C. pubescens R. & P., and C. chinense Jacq.), and two isolates were selected via mycelial growth inhibition assays based on their production of volatile organic compounds (VOCs) against six fungal strains. Genomic analysis identified these isolates as Bacillus altitudinis CH05, with a chromosome size of 3,687,823 bp and with 41.25% G+C, and Bacillus tropicus CH13, with a chromosome size of 5,283,706 bp and with 35.24% G+C. Both bacterial strains showed high mycelial growth inhibition capacities against Sclerotium rolfsii , Sclerotinia sp., Rhizoctonia solani , and Alternaria alternata but lower inhibition capacities against Colletotrichum gloesporoides and Fusarium oxysporum . VOC identification was carried out after 24 h of fermentation with 64 VOCs for B. altitudinis CH05 and 53 VOCs for B. tropicus CH13. 2,5-Dimethyl pyrazine and acetoin had the highest relative abundance values in both bacterial strains. Our findings revealed that seed-surface-associated bacteria on Capsicum spp. have the metabolic ability to produce VOCs for biocontrol of fungal strains and have the potential to be used in sustainable agriculture.
Published: 2024
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15. Estimation of the difference between peritoneal microenvironment and core body temperature during laparoscopic surgery - a prospective observational study.

Author: Mazzinari G, Rovira L, Vila Montañes M, García Gregorio N, Ayas Montero B, Alberola Estellés MJ, Flor B, Argente Navarro MP, and Diaz-Cambronero O
Subjects: Humans, Female, Male, Prospective Studies, Middle Aged, Aged, Peritoneum surgery, Hypothermia prevention & control, Hypothermia etiology, Adult, Insufflation methods, Pneumoperitoneum, Artificial methods, Peritoneal Cavity surgery, Laparoscopy methods, Body Temperature, Carbon Dioxide
Abstract: Maintaining patients' temperature during surgery is beneficial since hypothermia has been linked with perioperative complications. Laparoscopic surgery involves the insufflation of carbon dioxide (CO 2 ) into the peritoneal cavity and has become the standard in many surgical indications since it is associated with better and faster recovery. However, the use of cold and dry CO 2 insufflation can lead to perioperative hypothermia. We aimed to assess the difference between intraperitoneal and core temperatures during laparoscopic surgery and evaluate the influence of duration and CO 2 insufflation volume by fitting a mixed generalized additive model. In this prospective observational single-center cohort trial, we included patients aged over 17 with American Society of Anesthesiology risk scores I to III undergoing laparoscopic surgery. Anesthesia, ventilation, and analgesia followed standard protocols, while patients received active warming using blankets and warmed fluids. Temperature data, CO 2 ventilation parameters, and intraabdominal pressure were collected. We recruited 51 patients. The core temperature was maintained above 36 °C and progressively raised toward 37 °C as pneumoperitoneum time passed. In contrast, the intraperitoneal temperature decreased, thus creating a widening difference from 0.4 [25th-75th percentile: 0.2-0.8] °C at the beginning to 2.3 [2.1-2.3] °C after 240 min. Pneumoperitoneum duration and CO 2 insufflation volume significantly increased this temperature difference (P < 0.001 for both parameters). Core vs. intraperitoneal temperature difference increased linearly by 0.01 T °C per minute of pneumoperitoneum time up to 120 min and then 0.05 T °C per minute. Each insufflated liter per unit of time, i.e. every 10 min, increased the temperature difference by approximately 0.009 T °C. Our findings highlight the impact of pneumoperitoneum duration and CO 2 insufflation volume on the difference between core and intraperitoneal temperatures. Implementing adequate external warming during laparoscopic surgery effectively maintains core temperature despite the use of dry and unwarmed CO 2 gases, but peritoneal hypothermia remains a concern, suggesting the importance of further research into regional effects.Trial registration: Clinicaltrials.gov: NCT04294758., (© 2024. The Author(s).)
Published: 2024
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16. Role of Volatile Organic Compounds Produced by Kosakonia cowanii Cp1 during Competitive Colonization Interaction against Pectobacterium aroidearum SM2.

Author: Mena Navarro MP, Espinosa Bernal MA, Martinez-Avila AE, Aponte Pineda LS, Montes Flores LA, Chan Ku CD, Hernández Gómez YF, González Espinosa J, Pacheco Aguilar JR, Ramos López MÁ, Arvizu Gómez JL, Saldaña Gutierrez C, Rodríguez Morales JA, Amaro Reyes A, Hernández Flores JL, and Campos Guillén J
Abstract: The competitive colonization of bacteria on similar ecological niches has a significant impact during their establishment. The synthesis speeds of different chemical classes of molecules during early competitive colonization can reduce the number of competitors through metabolic effects. In this work, we demonstrate for the first time that Kosakonia cowanii Cp1 previously isolated from the seeds of Capsicum pubescens R. P. produced volatile organic compounds (VOCs) during competitive colonization against Pectobacterium aroidearum SM2, affecting soft rot symptoms in serrano chili ( Capsicum annuum L.). The pathogen P. aroidearum SM2 was isolated from the fruits of C. annuum var. Serrano with soft rot symptoms. The genome of the SM2 strain carries a 5,037,920 bp chromosome with 51.46% G + C content and 4925 predicted protein-coding genes. It presents 12 genes encoding plant-cell-wall-degrading enzymes (PCDEWs), 139 genes involved in five types of secretion systems, and 16 genes related to invasion motility. Pathogenic essays showed soft rot symptoms in the fruits of C. annuum L., Solanum lycopersicum , and Physalis philadelphica and the tubers of Solanum tuberosum . During the growth phases of K. cowanii Cp1, a mix of VOCs was identified by means of HS-SPME-GC-MS. Of these compounds, 2,5-dimethyl-pyrazine showed bactericidal effects and synergy with acetoin during the competitive colonization of K. cowanii Cp1 to completely reduce soft rot symptoms. This work provides novel evidence grounding a better understanding of bacterial interactions during competitive colonization on plant tissue, where VOC synthesis is essential and has a high potential capacity to control pathogenic microorganisms in agricultural systems.
Published: 2024
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17. A Study of Resistome in Mexican Chili Powder as a Public Health Risk Factor.

Author: Mena Navarro MP, Espinosa Bernal MA, Alvarado Osuna C, Ramos López MÁ, Amaro Reyes A, Arvizu Gómez JL, Pacheco Aguilar JR, Saldaña Gutiérrez C, Pérez Moreno V, Rodríguez Morales JA, García Gutiérrez MC, Álvarez Hidalgo E, Nuñez Ramírez J, Hernández Flores JL, and Campos Guillén J
Abstract: Chili powder is an important condiment around the world. However, according to various reports, the presence of pathogenic microorganisms could present a public health risk factor during its consumption. Therefore, microbiological quality assessment is required to understand key microbial functional traits, such as antibiotic resistance genes (ARGs). In this study, metagenomic next-generation sequencing (mNGS) and bioinformatics analysis were used to characterize the comprehensive profiles of the bacterial community and antibiotic resistance genes (ARGs) in 15 chili powder samples from different regions of Mexico. The initial bacterial load showed aerobic mesophilic bacteria (AMB) ranging between 6 × 10 3 and 7 × 10 8 CFU/g, sporulated mesophilic bacteria (SMB) from 4.3 × 10 3 to 2 × 10 9 CFU/g, and enterobacteria (En) from <100 to 2.3 × 10 6 CFU/g. The most representative families in the samples were Bacillaceae and Enterobacteriaceae , in which 18 potential pathogen-associated species were detected. In total, the resistome profile in the chili powder contained 68 unique genes, which conferred antibiotic resistance distributed in 13 different classes. Among the main classes of antibiotic resistance genes with a high abundance in almost all the samples were those related to multidrug, tetracycline, beta-lactam, aminoglycoside, and phenicol resistance. Our findings reveal the utility of mNGS in elucidating microbiological quality in chili powder to reduce the public health risks and the spread of potential pathogens with antibiotic resistance mechanisms.
Published: 2024
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18. Quantum Molecular Resonance Radiofrequency Disc Decompression and Percutaneous Microdiscectomy for Lumbar Radiculopathy.

Author: Canós-Verdecho Á, Robledo R, Izquierdo RM, Bermejo A, Gallach E, Abejón D, Argente-Navarro MP, Peraita-Costa I, and Morales-Suárez-Varela M
Abstract: Within the practice of pain management, one of the most commonly encountered events is low back pain. Lumbar radiculopathy (LR) is a pain syndrome caused by the compression or irritation of the nerve roots in the lower back due to lumbar disc herniation, vertebra degeneration, or foramen narrowing. Symptoms of LR include low back pain that propagates toward the legs, numbness, weakness, and loss of reflexes. The aim of this study is to assess the long-term effectiveness of quantum molecular resonance disc decompression and its combination with a percutaneous microdiscectomy using Grasper© forceps (QMRG) in patients with persistent lumbar radiculopathy (LR) in relation to patient physical stress status. The main outcome measures of this prospective observational study were DN4, NRS, ODI, SF12, PGI, CGI, and MOS Sleep Scale. An improvement 12 months post-intervention was observed in patients without physical stress, presenting better overall results. The mean change was over the minimal clinically important difference in 64.3% of outcome measures studied for the whole sample. QMRG appears to be an effective treatment option for LR, but a reduction in physical stress is needed to ensure long-term effectiveness.
Published: 2023
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19. Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Author: García-Carmona JA, García-Pérez A, Isidro García G, Forcen-Muñoz LA, Ovejero García S, Sáez Povedano R, González-Galdámez AL, Mata Iturralde L, Hernández-Sánchez F, Ramirez Bonilla M, Fuentes-Pérez P, Ovejas-Catalán C, Suárez-Pinilla P, Valdivia-Muñoz F, Fernández Abascal B, Omaña Colmenares M, de Lourdes Martín-Pérez Á, Campos-Navarro MP, Baca-García E, Benavente-López S, Raya Platero A, Barberán Navalón M, Sánchez-Alonso S, Vázquez-Bourgon J, and Pappa S
Abstract: Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions., Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment., Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration)., Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%., Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice., Competing Interests: JAGC received speaking honoraria from Janssen-Cilag Inc., advisor honoraria from Teva and research and speaking honoraria from Neuraxpharm, all of them outside the submitted work. Sofia Pappa reports grants and honoraria outside the submitted work. Other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)
Published: 2023
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20. An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

Author: Díaz-Cambronero Ó, Mazzinari G, Errando CL, Garutti I, Gurumeta AA, Serrano AB, Esteve N, Montañes MV, Neto AS, Hollmann MW, Schultz MJ, and Argente Navarro MP
Subjects: Humans, Cross-Over Studies, Postoperative Complications epidemiology, Postoperative Complications prevention & control, Anesthesia, General, Neostigmine, Delayed Emergence from Anesthesia, Neuromuscular Blockade
Abstract: Background: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it., Methods: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models., Results: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001)., Conclusions: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications., Clinical Trial Registration: NCT03128151., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
Published: 2023
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21. Effects of high-intensity interval training with an eccentric hamstring exercise program in futsal players: A randomized controlled trial.

Author: Gómez EM, Atef H, Elsayed SH, Zakaria HM, Navarro MP, and Sulé EM
Subjects: Humans, Young Adult, Adult, Exercise, Exercise Therapy, High-Intensity Interval Training, Sports, Hamstring Muscles
Abstract: Background: Physiotherapy protocols based on high-intensity interval training (HIIT) or eccentric hamstring exercises like Nordic Curl (NC) have been scarcely studied in futsal players. The objective of this study was to compare the effectiveness of a HIIT combined with an NC exercise program versus a HIIT-only program in futsal players., Methods: Twenty-one futsal players were divided into (1) HIIT + NC group (n = 11, mean age = 21.55 [4.25]); and (2) HIIT group (n = 10, mean age = 20.90 [1.29]). The HIIT + NC group performed a HIIT circuit combined with 3 sets of 10 NC repetitions for 4 weeks, while the HIIT group performed the same protocol without NC exercise. Body mass index, intermittent work performance, vertical jump performance without and with arms, isometric strength of quadriceps and hamstrings, and the isometric hamstrings/quadriceps (H/Q) ratio, were assessed before and after the interventions., Results: The HIIT + NC group and the HIIT group showed a significant improvement in intermittent work performance after the intervention (P = .04 and P = .01, respectively). Also, both groups showed a trend of increasing quadriceps and hamstring isometric strength, although no significant changes were found (P > .05). In addition, neither the HIIT + NC protocol nor the HIIT protocol was sufficient to yield changes in body mass index nor to improve the vertical jump performance (P > .05)., Conclusion: Both an isolated HIIT protocol and HIIT in combination with NC exercise improved intermittent work performance in futsal players. The present study's findings may guide futsal players' physical preparation and injury prevention programs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
Published: 2023
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22. Frequency of symptoms and the associated factors of eating disorders in a group of dental students in Medellín, Colombia.

Author: Sanjuán-Navarro PS, Agudelo-Suárez AA, Mora-Cárdenas AL, Angarita-Navarro MP, Valdés-Payares L, Martínez-Gómez ML, and Salazar-González CL
Subjects: Male, Adolescent, Humans, Female, Cross-Sectional Studies, Colombia epidemiology, Students, Dental, Pandemics, Feeding and Eating Disorders epidemiology
Abstract: Background: Eating disorders (EDs) are considered a public health problem. Scientific research has focused on teenagers due to their higher prevalence in this population. However, other groups, such as university students, may be exposed to suffering from EDs due to their academic, social and personal characteristics. Identifying the magnitude of EDs and the associated characteristics may impact the generation of prevention strategies., Objectives: The aim of the present study was to establish the prevalence of the risk of EDs (anorexia nervosa (AN) and bulimia nervosa (BN)) and the associated factors in dental students at the University of Antioquia, Medellín, Colombia.., Material and Methods: A cross-sectional study was conducted on 278 students (76 males, 202 females) with the use of a Google-Forms survey. The validated Spanish version of the Eating Attitudes Test-26 (EAT-26) and the Sick, Control, One Stone, Fat, Food (SCOFF) questionnaire were used. Other recorded variables included sociodemographic data, coronavirus disease 2019 (COVID-19)-related factors, health, and social support (the Duke-11 profile). The bivariate analysis of the risk of EDs was conducted according to different variables (95% confidence interval (CI)), followed by the logistic regression models adjusting for different variables (adjusted prevalence ratio (aPR) and 95% CI)., Results: According to EAT-26, the risk of EDs was 27.6% (18.8-38.6) for males and 28.7% (22.9-35.3) for females. However, differences between males and females were higher when the SCOFF questionnaire was applied (males: 6.6% (2.8-14.5); females: 22.3% (17.1-28.5); p < 0.01). According to the SCOFF instrument, after adjusting for sociodemographic and health variables, women were more likely to report the symptoms of EDs (aPR: 2.20; 95% CI: 1.06-4.57). Women receiving information from social networks were more likely to report the symptoms of EDs (aPR: 1.85; 95% CI: 1.19-2.88). Multivariate models showed that women reporting poor self-rated health and some symptoms during the mandatory confinement caused by the COVID-19 pandemic were more likely to report the symptoms of EDs., Conclusions: A higher risk of EDs was found in dental students. Healthcare, psychological and/or psychiatric interviews, and educational/early prevention strategies are required.
Published: 2023
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23. An Individualized Low-Pneumoperitoneum-Pressure Strategy May Prevent a Reduction in Liver Perfusion during Colorectal Laparoscopic Surgery.

Author: Olmedilla Arnal LE, Cambronero OD, Mazzinari G, Pérez Peña JM, Zorrilla Ortúzar J, Rodríguez Martín M, Vila Montañes M, Schultz MJ, Rovira L, Argente Navarro MP, and On Behalf Of The IPPColLapSe Ii Investigators
Abstract: High intra-abdominal pressure (IAP) during laparoscopic surgery is associated with reduced splanchnic blood flow. It is uncertain whether a low IAP prevents this reduction. We assessed the effect of an individualized low-pneumoperitoneum-pressure strategy on liver perfusion. This was a single-center substudy of the multicenter 'Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy II study' (IPPCollapse-II), a randomized clinical trial in which patients received an individualized low-pneumoperitoneum strategy (IPP) or a standard pneumoperitoneum strategy (SPP). Liver perfusion was indirectly assessed by the indocyanine green plasma disappearance rate (ICG-PDR) and the secondary endpoint was ICG retention rate after 15 min (R 15 ) using pulse spectrophotometry. Multivariable beta regression was used to assess the association between group assignment and ICG-PDR and ICG-R 15 . All 29 patients from the participating center were included. Median IAP was 8 (25th-75th percentile: 8-10) versus 12 (12,12) mmHg, in IPP and SPP patients, respectively ( p < 0.001). ICG-PDR was higher (OR 1.42, 95%-CI 1.10-1.82; p = 0.006) and PDR-R 15 was lower in IPP patients compared with SPP patients (OR 0.46, 95%-CI 0.29-0.73; p = 0.001). During laparoscopic colorectal surgery, an individualized low pneumoperitoneum may prevent a reduction in liver perfusion.
Published: 2023
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24. Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

Author: Belltall A, Mazzinari G, Diaz-Cambronero O, Eroles P, and Argente Navarro MP
Subjects: Cell Proliferation, Humans, Naltrexone analogs & derivatives, Quaternary Ammonium Compounds, Receptors, Opioid metabolism, Narcotic Antagonists pharmacology, Narcotic Antagonists therapeutic use, Neoplasms drug therapy, Neoplasms metabolism
Abstract: Purpose of Review: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action., Recent Findings: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects., (© 2022. The Author(s).)
Published: 2022
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25. Thermal and Rheological Characterization of Aqueous Nanofluids Based on Reduced Graphene Oxide (rGO) with Manganese Dioxide Nanocomposites (MnO 2 ).

Author: Lozano-Steinmetz F, Ramírez-Navarro MP, Vivas L, Vasco DA, Singh DP, and Zambra-Sazo C
Abstract: Nanofluids have become of interest in recent years thanks to their improved thermal properties, which make them especially interesting for microchannel heat sink applications. In this study, we prepared two aqueous nanofluids based on reduced graphene oxide (rGO) decorated with manganese dioxide (MnO2) at a concentration of 0.1 wt.%. The difference between the two nanofluids was in the preparation of the reduced graphene oxide decorated with MnO2. In the first case, the manganese salt was mixed with ascorbic acid before GO reduction with NaOH, and in the second case, the GO reduction with NaOH occurred under ascorbic acid. Ascorbic acid not only plays the role of a non-toxic and ecofriendly reducing agent but also acts as an important parameter to control the reaction kinetics. The structural, microstructural and spectral characterizations of the MnO2/rGO nanocomposite were conducted via X-ray diffractometry (XRD), Raman spectroscopy, FT-IR, TEM, SEM and EDS analyses. Moreover, the synthesized MnO2/rGO nanocomposites were utilized as nanofluids and their stability, thermal conductivity and rheological behaviors were studied. The thermal conductivity of the MnO2/rGO and MnO2AsA/rGO nanofluids was 17% and 14.8% higher than that of water for the average temperature range, respectively, but their viscosity remained statistically equal to that of water. Moreover, both nanofluids presented Newtonian behavior in the analyzed shear rate range. Therefore, both MnO2/rGO and MnO2AsA/rGO nanofluids are promising alternatives for use in applications with micro- and millichannel heat sinks.
Published: 2022
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26. Retrospective observational study on safety of sedation for colonoscopies in ASA I and II patients performed by a nurse and under the supervision of anesthesiology.

Author: Monsma-Muñoz M, Romero-García E, Montero-Sánchez F, Tevar-Yudego J, Silla-Aleixandre I, Pons-Beltrán V, and Argente-Navarro MP
Subjects: Bradycardia, Colonoscopy, Humans, Hypnotics and Sedatives adverse effects, Anesthesiology, Propofol adverse effects
Abstract: Introduction: Out of operating room sedation with propofol by non-anaesthesiologists (Non Anaesthesiologist Administration of Propofol: NAAP) is a growing practice. This is due to the increase in minimally invasive diagnostic and therapeutic procedures requiring sedation, and the difficulty of anaesthesiology services to respond adequately to this demand., Objective: The main objective of this study is to assess the safety of a programme of nurse sedationist-administered target controlled infusion (TCI) of propofol in colonoscopies supervised by anaesthesiologists., Material and Methods: Over a period of 6 months, all ASA I and II patients who required colonoscopy and met the inclusion criteria were included in the study. A total of 381 colonoscopies were performed. Episodes of desaturation, hypo- or hypertension, bradycardia or tachyarrhythmia and the need for anaesthesiology assistance during sedation were analysed. After the procedure, patient satisfaction was assessed on a scale of 1-5, and pain was assessed on a numerical verbal scale of 1-5., Results: A small percentage (5%) of patients presented oxygen saturation of less than 90%, without requiring mask ventilation; 7.35% presented hypotension, 3.94% presented bradycardia, and the supervising anaesthesiologist was called in 22% of cases. Patient satisfaction at the end of the procedure was 4.27 out of 5., Conclusion: Sedation during colonoscopy in ASA I and II patients following an agreed protocol can be safely administered by nurse sedationists under the supervision of an anaesthesiologist., (Copyright © 2021 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)
Published: 2022
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27. Opioid Receptor Expression in Colorectal Cancer: A Nested Matched Case-Control Study.

Author: Belltall A, Mazzinari G, Garrido-Cano I, Giner F, Marí AM, Eroles P, Argente-Navarro MP, Cata JP, and Diaz-Cambronero O
Abstract: Background: There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC)., Methods: Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx)., Results: There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence., Conclusion: In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an in silico analysis of samples from the TCGA-GTEx database., Competing Interests: OD-C: Received payment for educational talks and scientific conferences from MSD (Merck Sharp & Dohme, Inc.). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Belltall, Mazzinari, Garrido-Cano, Giner, Marí, Eroles, Argente-Navarro, Cata and Diaz-Cambronero.)
Published: 2022
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28. Prevalence of inappropriate prescribing in complex chronic patients: Time trends in a health department of Valencia, Spain (2015-2019).

Author: Peris-Campillo P, Trillo-Mata JL, Roca-Navarro MP, Usó-Talamantes R, and Navarro-Pérez J
Subjects: Aged, Humans, Prevalence, Spain epidemiology, Inappropriate Prescribing, Prescriptions
Abstract: Background and Objective: Inappropriate prescribing (IP) is an important cause of health problems among elderly and complex chronic patients (CCPs)., Objective: Surveillance of IP prevalence among elderly and CCPs in a health department. IP time trends across the period 2015-2019., Method: Descriptive population-based study., Setting: 'València-Clínic-Malvarrosa' Health Department, Valencia, Spain., Period: 2015-2019., Subjects: Complete set of CCPs in the department, defined by clinical risk groups. Number of CCPs (annual average in the period): 9102 (75% ≥65 years of age). IP was measured using an indicator consisting of 13 specific types of prescriptions defined as inappropriate., Analyses: frequencies and time trends, both overall and by specific type., Results: Overall prevalence of IP ranged from 0.276 (2015) to 0.289 (2018) per patient, without time trend. The most frequent inappropriate prescription was type 1: "≥75 years of age with inappropriate medication", which showed a stable rate across the period. Some types of inappropriate prescriptions displayed favourable decreasing time trends, while others showed no change or an unfavourable trend (i.e., joint prescription of absorbents and urinary antispasmodics)., Conclusions: IP prevalence is a serious and persistent problem among the elderly and CCPs, especially in the oldest. It is therefore necessary its continuous surveillance (overall and by specific types of prescription). As well as interventions to optimise prescribing, thus improving the quality and efficiency of care for the elderly and CCPs., (Copyright © 2022 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)
Published: 2022
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29. Off-label use of second-generation antipsychotics in borderline personality disorder: a comparative real-world study among oral and long-acting injectables in Spain.

Author: García-Carmona JA, Simal-Aguado J, Campos-Navarro MP, Valdivia-Muñoz F, and Galindo-Tovar A
Subjects: Administration, Oral, Delayed-Action Preparations, Humans, Injections, Spain, Antipsychotic Agents administration & dosage, Borderline Personality Disorder drug therapy, Off-Label Use statistics & numerical data
Abstract: The aim of the present study was to evaluate the use of oral vs. long-acting injectables (LAIs) antipsychotics, as well as, to compare the effectiveness of different LAI antipsychotics [aripiprazole-1-month, paliperidone-1-month (PP1M), paliperidone-3-month (PP3M) and risperidone long-acting injectable (RLAI)] in patients diagnosed with borderline personality disorder (BPD), by evaluating the following clinical outcomes: (1) the number of hospital admissions; (2) the number of documented suicidal behaviour/attempts; and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics and biperiden. We included a total of 116 patients diagnosed with BPD and treated with antipsychotic medication: 50 using a LAI antipsychotic formulation and 66 using the equivalent main oral antipsychotic. Patients treated with LAIs showed a decreased ratio of visits to emergency compared with the oral treatment group, and between LAIs, PP3M vs. aripiprazole-1-month group. Furthermore, patients treated with LAIs used lower number and dose of concomitant antipsychotics compared with patients treated with oral antipsychotics. Moreover, PP1M and PP3M used lower daily dose of diazepam equivalents compared with the aripiprazole-1-month and RLAI treatment groups. In conclusion, the use of LAIs may play a role in the management of BPD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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30. Modeling intra-abdominal volume and respiratory driving pressure during pneumoperitoneum insufflation-a patient-level data meta-analysis.

Author: Mazzinari G, Diaz-Cambronero O, Serpa Neto A, Martínez AC, Rovira L, Argente Navarro MP, Malbrain MLNG, Pelosi P, Gama de Abreu M, Hollmann MW, and Schultz MJ
Subjects: Abdomen, Adult, Bayes Theorem, Humans, Pneumoperitoneum, Artificial, Abdominal Cavity, Insufflation, Laparoscopy, Pneumoperitoneum
Abstract: During pneumoperitoneum, intra-abdominal pressure (IAP) is usually kept at 12-14 mmHg. There is no clinical benefit in IAP increments if they do not increase intra-abdominal volume IAV. We aimed to estimate IAV (ΔIAV) and respiratory driving pressure changes (Δ P RS ) in relation to changes in IAP (ΔIAP). We carried out a patient-level meta-analysis of 204 adult patients with available data on IAV and Δ P RS during pneumoperitoneum from three trials assessing the effect of IAP on postoperative recovery and airway pressure during laparoscopic surgery under general anesthesia. The primary endpoint was ΔIAV, and the secondary endpoint was Δ P RS . The endpoints' response to ΔIAP was modeled using mixed multivariable Bayesian regression to estimate which mathematical function best fitted it. IAP values on the pressure-volume (PV) curve where the endpoint rate of change according to IAP decreased were identified. Abdomino-thoracic transmission (ATT) rate, that is, the rate Δ P RS change to ΔIAP was also estimated. The best-fitting function was sigmoid logistic and linear for IAV and Δ P RS response, respectively. Increments in IAV reached a plateau at 6.0 [95%CI 5.9-6.2] L. ΔIAV for each ΔIAP decreased at IAP ranging from 9.8 [95%CI 9.7-9.9] to 12.2 [12.0-12.3] mmHg. ATT rate was 0.65 [95%CI 0.62-0.68]. One mmHg of IAP raised Δ P RS 0.88 cmH 2 O. During pneumoperitoneum, IAP has a nonlinear relationship with IAV and a linear one with Δ P RS . IAP should be set below the point where IAV gains diminish. NEW & NOTEWORTHY We found that intra-abdominal volume changes related to intra-abdominal pressure increase reached a plateau with diminishing gains in commonly used pneumoperitoneum pressure ranges. We also found a linear relationship between intra-abdominal pressure and respiratory driving pressure, a known marker of postoperative pulmonary complications.
Published: 2021
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31. Evaluation of Risk Factors Associated to Prescription of Benzodiazepines and its Patterns in a Cohort of Patients from Mental Health: A Real World Study in Spain.

Author: Simal-Aguado J, Campos-Navarro MP, Valdivia-Muñoz F, Galindo-Tovar A, and García-Carmona JA
Subjects: Drug Prescriptions, Female, Humans, Risk Factors, Spain, Benzodiazepines adverse effects, Mental Health
Abstract: Purpose: we aimed 1) to evaluate the risk factors associated to the benzodiazepines intake; 2) to assess the impact about the use of long acting injectables antipsychotics (LAIs); 3) to assess the risk in severe and affective disorders and 4) to identify the prescription patterns of use in mental health in a cohort of patients from Spain., Methods: 735 outpatients from Mental Health were included. Demographic and clinical data were collected. In order to compare the use of benzodiazepines we calculated the daily dose equivalents (mg/day) to diazepam as standard., Results: The most commonly prescribed benzodiazepine was clonazepam (33%) and the mean daily dose of diazepam equivalents was 24.9 mg. It was higher in affective disorders (40.35 ± 3.36) and lower in patients using LAIs antipsychotics (17.50 ± 1.39; p = 0.001). Multivariate analysis showed that to be women (OR = 1.559, 95% CI = 1.059-2.295, p = 0.024), the use of drugs (OR = 1.671, 95% CI = 1.127-2.477, p = 0.011) and suffering any affective disorder (OR = 1.542, 95% CI = 1.355-1.826, p = 0.040) increased the risk of benzodiazepine intake. In contrast, the use of LAIs antipsychotics significantly reduced it versus oral antipsychotics (OR = 5.226, 95% CI = 3.185-8.575, p = 0.001)., Conclusions: benzodiazepines are widely prescribed, mainly clonazepam followed by lorazepam and diazepam. Most of patients used at least one benzodiazepine and the mean daily intake was 25 mg diazepam equivalents. Therefore, benzodiazepines are extensively prescribed and used at higher doses than desirable. These, findings could be useful for clinicians and their practice., (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)
Published: 2021

32. Evaluation of long-acting injectable antipsychotics with the corresponding oral formulation in a cohort of patients with schizophrenia: a real-world study in Spain.

Author: García-Carmona JA, Simal-Aguado J, Campos-Navarro MP, Valdivia-Muñoz F, and Galindo-Tovar A
Subjects: Administration, Oral, Adolescent, Adult, Cohort Studies, Delayed-Action Preparations, Humans, Injections, Spain, Treatment Outcome, Antipsychotic Agents administration & dosage, Schizophrenia drug therapy
Abstract: To date, only a few studies compared some long-acting injectables (LAIs) antipsychotics showing similar symptom improvement, relapse rates and adherence to treatment. We evaluated the use of LAIs antipsychotics [aripiprazole-1-month (A1M); paliperidone-1-month and 3-month (PP1M and PP3M) and biweekly (2w)-LAIs] and their corresponding oral formulations through (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviour/attempts and (3) the use of concomitant benzodiazepines, oral antipsychotics and biperiden. A total of 277 patients, ≥18 years old, were included if were treated with the corresponding oral or LAI antipsychotic during at least 12 months and were previously diagnosed with schizophrenia. Our results showed that LAIs associated significantly lower suicidal behaviour, reduced the number of hospital admissions, lower diazepam and haloperidol equivalents and mean daily dose of biperiden intake versus oral antipsychotics. Furthermore, significant differences were found between LAIs. Specifically, PP3M was associated to lower hospital admissions versus A1M; PP1M and PP3M lower doses of diazepam equivalents versus 2w-LAIs and finally, PP1M lower antipsychotic intake versus 2w-LAIs. In conclusion, LAIs improved clinical outcomes by reducing the need for concomitant treatments and hospital admissions over oral antipsychotics. PP1M and PP3M showed better outcomes versus A1M and biweekly LAIs.
Published: 2021
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33. Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study.

Author: López-Sánchez M, Moreno-Puigdollers I, Rubio-López MI, Zarragoikoetxea-Jauregui I, Vicente-Guillén R, and Argente-Navarro MP
Subjects: Adult, Aged, Antifungal Agents administration & dosage, Area Under Curve, Female, Half-Life, Humans, Male, Micafungin administration & dosage, Middle Aged, Prospective Studies, Tertiary Care Centers, Tissue Distribution, Antifungal Agents pharmacokinetics, Extracorporeal Membrane Oxygenation, Micafungin pharmacokinetics
Abstract: Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation., Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated., Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843., Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.
Published: 2020
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34. Long-Acting Injectable Antipsychotics: Analysis of Prescription Patterns and Patient Characteristics in Mental Health from a Spanish Real-World Study.

Author: García-Carmona JA, Simal-Aguado J, Campos-Navarro MP, Valdivia-Muñoz F, and Galindo-Tovar A
Subjects: Adult, Female, Humans, Male, Patient Readmission, Schizophrenia drug therapy, Spain, Antipsychotic Agents administration & dosage, Delayed-Action Preparations administration & dosage, Drug Prescriptions, Mental Health
Abstract: Background and Objective: Long-acting injectable antipsychotics (LAIs) have been widely studied in schizophrenia and evidence suggests that they could be also used for the treatment of bipolar and schizoaffective disorders. Nonetheless, there are no studies evaluating their role in other psychiatric disorders. We aimed to evaluate the use of the newest monthly and 3-monthly LAIs-aripiprazole once monthly, paliperidone 1- and 3-monthly (PP1M, PP3M)-against the 2-weekly LAIs, using the following clinical outcomes: (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviors/attempts, and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics, and biperiden., Methods: A total of 431 patients were included who were treated with the corresponding LAI over at least 12 months and were previously diagnosed with a psychiatric disorder. Statistical analyses were performed using an ANCOVA model, Student's t test, and the Pearson's r test., Results: Our results showed significantly decreased re-admissions using PP3M versus the bi-weekly LAIs and aripiprazole once monthly, while no significant differences were found in suicidal behavior. Furthermore, we found a significantly lower intake of benzodiazepines in PP1M and PP3M groups versus the bi-weekly and aripiprazole once-monthly groups. In addition, patients treated with PP1M and PP3M used a significantly lower dose of haloperidol equivalents versus the bi-weekly LAIs group. Finally, significantly higher doses of biperiden were used by the bi-weekly LAIs group., Conclusion: In conclusion, paliperidone LAIs reduced hospital re-admissions and, as aripiprazole once monthly, lowered concomitant psychiatric medication versus the bi-weekly LAIs. Further research and analysis of subgroups are needed; however, these findings might be useful for clinicians.
Published: 2020
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35. Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study.

Author: Díaz-Cambronero O, Mazzinari G, Giner F, Belltall A, Ruiz-Boluda L, Marqués-Marí A, Sánchez-Guillén L, Eroles P, Cata JP, and Argente-Navarro MP
Abstract: Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. The primary endpoint was five years of DFS. Secondary endpoints were five years of OS, the difference in MOR-1 expression between normal and tumor tissue and the occurrence of postoperative complications. Multivariable Cox regression showed no significant association between MOR-1 expression and DFS (HR 0.791, 95% CI 0.603-1.039, p = 0.092). MOR-1 expression was higher in tumor tissue compared to non-tumor tissue. No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.
Published: 2020
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36. An individualised versus a conventional pneumoperitoneum pressure strategy during colorectal laparoscopic surgery: rationale and study protocol for a multicentre randomised clinical study.

Author: Diaz-Cambronero O, Mazzinari G, Errando CL, Schultz MJ, Flor Lorente B, García-Gregorio N, Vila Montañés M, Robles-Hernández D, Olmedilla Arnal LE, Martín-De-Pablos A, Marqués Marí A, and Argente Navarro MP
Subjects: Colon physiopathology, Digestive System Surgical Procedures adverse effects, Humans, Length of Stay, Multicenter Studies as Topic, Pneumoperitoneum, Artificial adverse effects, Postoperative Complications etiology, Pressure, Randomized Controlled Trials as Topic, Recovery of Function, Rectum physiopathology, Single-Blind Method, Spain, Time Factors, Treatment Outcome, Colon surgery, Digestive System Surgical Procedures methods, Laparoscopy adverse effects, Pneumoperitoneum, Artificial methods, Rectum surgery
Abstract: Background: A recent study shows that a multifaceted strategy using an individualised intra-abdominal pressure titration strategy during colorectal laparoscopic surgery results in an acceptable workspace at low intra-abdominal pressure in most patients. The multifaceted strategy, focused on lower to individualised intra-abdominal pressures, includes prestretching the abdominal wall during initial insufflation, deep neuromuscular blockade, low tidal volume ventilation settings and a modified lithotomy position. The study presented here tests the hypothesis that this strategy improves outcomes of patients scheduled for colorectal laparoscopic surgery., Methods: The Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy (IPPCollapse-II) study is a multicentre, two-arm, parallel-group, single-blinded randomised 1:1 clinical study that runs in four academic hospitals in Spain. Patients scheduled for colorectal laparoscopic surgery with American Society of Anesthesiologists classification I to III who are aged > 18 years and are without cognitive deficits are randomised to an individualised pneumoperitoneum pressure strategy (the intervention group) or to a conventional pneumoperitoneum pressure strategy (the control group). The primary outcome is recovery assessed with the Post-operative Quality of Recovery Scale (PQRS) at postoperative day 1. Secondary outcomes include PQRS score in the post anaesthesia care unit and at postoperative day 3, postoperative complications until postoperative day 28, hospital length of stay and process-related outcomes., Discussion: The IPPCollapse-II study will be the first randomised clinical study that assesses the impact of an individualised pneumoperitoneum pressure strategy focused on working with the lowest intra-abdominal pressure during colorectal laparoscopic surgery on relevant patient-centred outcomes. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance for optimising the care and safety of laparoscopic abdominal surgery. Selection of patient-reported outcomes as the primary outcome of this study facilitates the translation into clinical practice. Access to source data will be made available through anonymised datasets upon request and after agreement of the Steering Committee of the IPPCollapse-II study., Trial Registration: ClinicalTrials.gov, NCT02773173 . Registered on 16 May 2016. EudraCT, 2016-001693-15. Registered on 8 August 2016.
Published: 2019
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37. Chronic Blockade of Brain Endothelin Receptor Type-A (ET A ) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats.

Author: Cassinotti LR, Guil MJ, Schöller MI, Navarro MP, Bianciotti LG, and Vatta MS
Subjects: Animals, Catecholamines pharmacology, Desoxycorticosterone Acetate adverse effects, Disease Models, Animal, Enzyme Activation drug effects, Gene Expression, Heart Rate drug effects, Hypertension physiopathology, Male, Phosphorylation, Rats, Tyrosine 3-Monooxygenase genetics, Tyrosine 3-Monooxygenase metabolism, Blood Pressure drug effects, Catecholamines metabolism, Endothelin A Receptor Antagonists pharmacology, Hypertension etiology, Hypertension metabolism, Olfactory Bulb drug effects, Olfactory Bulb metabolism, Receptor, Endothelin A metabolism
Abstract: Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET A ) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ET A blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ET A blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ET A are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension., Competing Interests: The authors declare no conflict of interest.
Published: 2018
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38. CRISPR-Cas systems: ushering in the new genome editing era.

Author: Perez Rojo F, Nyman RKM, Johnson AAT, Navarro MP, Ryan MH, Erskine W, and Kaur P
Subjects: Animals, Animals, Genetically Modified, CRISPR-Associated Protein 9 metabolism, DNA genetics, DNA metabolism, DNA End-Joining Repair, Humans, Patents as Topic, Plants genetics, Plants, Genetically Modified, RNA, Guide, CRISPR-Cas Systems metabolism, Transcription Activator-Like Effector Nucleases genetics, Transcription Activator-Like Effector Nucleases metabolism, CRISPR-Associated Protein 9 genetics, CRISPR-Cas Systems, Clustered Regularly Interspaced Short Palindromic Repeats, Gene Editing methods, Genome, RNA, Guide, CRISPR-Cas Systems genetics
Abstract: In recent years there has been great progress with the implementation and utilization of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) systems in the world of genetic engineering. Many forms of CRISPR-Cas9 have been developed as genome editing tools and techniques and, most recently, several non-genome editing CRISPR-Cas systems have emerged. Most of the CRISPR-Cas systems have been classified as either Class I or Class II and are further divided among several subtypes within each class. Research teams and companies are currently in dispute over patents for these CRISPR-Cas systems as numerous powerful applications are concurrently under development. This mini review summarizes the appearance of CRISPR-Cas systems with a focus on the predominant CRISPR-Cas9 system as well as the classifications and subtypes for CRISPR-Cas. Non-genome editing uses of CRISPR-Cas are also highlighted and a brief overview of the commercialization of CRISPR is provided.
Published: 2018
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39. Modifications in bacterial groups and short chain fatty acid production in the gut of healthy adult rats after long-term consumption of dietary Maillard reaction products.

Author: Delgado-Andrade C, Pastoriza de la Cueva S, Peinado MJ, Rufián-Henares JÁ, Navarro MP, and Rubio LA
Subjects: Animals, Diet, Fatty Acids, Volatile analysis, Feces chemistry, Feces microbiology, Maillard Reaction, Male, Rats, Rats, Wistar, Bacteria drug effects, Fatty Acids, Volatile metabolism, Gastrointestinal Microbiome drug effects, Glycation End Products, Advanced administration & dosage, Glycation End Products, Advanced pharmacology
Abstract: Bread crust (BC) is one of the major sources of Maillard reaction products (MRPs) in the Western diet. This work was designed to analyze the impact of diets containing important levels of MRPs from BC on intestinal bacterial growth and short chain fatty acids (SCFAs) production in adult rats. Additionally, the pools of compounds excreted in feces attending to their molecular weights were analyzed. Rats were fed for 88days a control diet or diets containing BC or its soluble high molecular weight (HMW), soluble low molecular weight (LMW) or insoluble fractions, respectively. Intestinal (cecum) microbiota composition was determined by qPCR analysis. Consumption of the BC diet lowered (P<0.05) Lactobacillus spp. and Bifidobacterium spp. log 10 counts (8 and 14%, respectively), an effect for which soluble LMW and HMW fractions of BC seemed to be responsible. In these same animals, Escherichia/Shigella counts increased by around 45% (P<0.05), a fact which correlated with a higher production of formic acid in feces (r=0.8197, P=0.0458), and likely caused by the combined consumption of all MRPs contained in the BC. A significant 5-fold increment (P<0.05) was detected in the fecal proportion of propionic acid in the BC group, one of the products that have largely been associated with anti-inflammatory actions. Regarding the distribution of MRPs in feces, only the LMW fed group exhibited a predominance of those ranging between 90,000-1000Da, whereas the rest of the groups presented higher amounts of products above 90,000Da. It is concluded that dietary Maillard reaction products are in vivo fermented by the gut microbiota, thereby changing both the pattern of SCFAs production and the microbiota composition., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
Published: 2017
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40. Do bread-crust-derived Maillard reaction products affect the retention and tissue distribution of trace elements?

Author: Delgado-Andrade C, Roncero-Ramos I, Haro A, Pastoriza S, and Navarro MP
Subjects: Animals, Biological Availability, Copper pharmacokinetics, Diet, Femur metabolism, Intestine, Small metabolism, Iron pharmacokinetics, Liver metabolism, Male, Rats, Rats, Wistar, Tissue Distribution, Zinc pharmacokinetics, Bread analysis, Maillard Reaction, Trace Elements pharmacokinetics
Abstract: Purpose: To investigate the effects of the consumption of Maillard reaction products (MRPs) from bread crust (BC) on iron, copper and zinc body retention and tissue distribution, determining whether these effects are related to the molecular weight of browning products., Methods: During an 88-day study period, rats were fed a Control diet or diets containing BC as source of MRPs, its soluble high or low molecular weight fractions (BC, LMW or HMW diets). A mineral balance was conducted throughout the experiment to determine iron, copper and zinc retention. At day 88, animals were killed, blood was drawn for haemoglobin determination and some organs removed to analyse minerals., Results: Copper and zinc balances were unchanged, and scant modification detected in their body delivery. However, the Fe retention rate from the diet increased (13, 22 and 32 % for BC, LMW and HMW diets), and a parallel higher Fe body concentration was observed (13-18 % higher than the Control group). Incoming iron accumulated particularly in the liver, femur and small intestine, but functional iron tended to decrease, as reflected by haemoglobin levels., Conclusions: The long-term intake of BC or derivatives did not produce a notable effect on copper or zinc balances, although slightly increased iron retention rate and the body concentration of this mineral were observed. Iron accumulated in some organs, but the production of haemoglobin was not improved. In view of the differences observed between the effects of BC and its derivatives, our results underline the importance of working with real food matrices, where the joint presence of different components modulates the in vivo final effects.
Published: 2016
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41. Assessing the effects of model Maillard compound intake on iron, copper and zinc retention and tissue delivery in adult rats.

Author: Roncero-Ramos I, Pastoriza S, Navarro MP, and Delgado-Andrade C
Subjects: Animals, Biological Availability, Diet, Food Handling methods, Glucose chemistry, Hemoglobins analysis, Hot Temperature, Iron physiology, Liver metabolism, Lysine chemistry, Rats, Rats, Wistar, Chelating Agents adverse effects, Chelating Agents chemistry, Copper pharmacokinetics, Iron, Dietary pharmacokinetics, Maillard Reaction, Zinc pharmacokinetics
Abstract: The behaviour of dietary Maillard reaction compounds (MRP) as metal chelating polymers can alter mineral absorption and/or retention. Our aim in this study was to analyse the long-term effects of the consumption of model MRP from glucose-lysine heated for 90 min at 150 °C (GL) on iron, copper and zinc whole-body retention and tissue delivery. For 88 days, weaning rats were fed a Control diet or one containing 3% GL, until reaching the adult stage. During the experimental period a mineral balance was conducted to investigate the mineral retention. At day 88, the animals were sacrificed, blood was drawn for haemoglobin determination and some organs were removed. Copper and zinc balances were unaffected (Cu: 450 vs. 375 μg; Zn: 6.7 vs. 6.2 mg for Control and GL groups, respectively) and no change was observed in whole-body delivery. Iron retention, too, was unaltered (11.2 mg for Control and GL groups) but due to the tendency toward decreased body weight in the GL group (248 vs. 233 g for the Control and GL groups), whole-body iron concentration was 13% higher in the GL group than in the Control group. Absorbed iron accumulated particularly in the liver (144 vs. 190 μg g(-1) for the Control and GL groups), thus reducing haemoglobin levels. The long-term intake of MRP induced iron accumulation in the body but this did not result in enhanced iron functionality, since the haemoglobin concentration declined. Taking into account the findings of our research group's studies of young and adult rats, we now corroborate the hypothesis that the negative effect of GL MRP consumption on iron functionality takes place regardless of the animals' stage of life.
Published: 2016
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42. Maillard reaction products modulate gut microbiota composition in adolescents.

Author: Seiquer I, Rubio LA, Peinado MJ, Delgado-Andrade C, and Navarro MP
Subjects: Adolescent, Animals, Bacteroides isolation & purification, Bifidobacterium isolation & purification, Cecum chemistry, Cecum microbiology, Cross-Over Studies, Diet, Enterobacteriaceae isolation & purification, Escherichia coli isolation & purification, Feces chemistry, Feces microbiology, Furaldehyde analogs & derivatives, Furaldehyde metabolism, Humans, Lactobacillus isolation & purification, Lysine analogs & derivatives, Lysine metabolism, Male, Rats, Rats, Wistar, Shigella isolation & purification, Intestines microbiology, Maillard Reaction, Microbiota
Abstract: Scope: Scarce data are available concerning effects of certain bioactive substances such as Maillard reaction products (MRP) on the gut microbiota composition, and the question of how a diet rich in MRP affects gut microbiota in humans is still open., Methods and Results: Two experiments were conducted. In expt. 1, adolescents consumed diets either high or low in MRP in a two-period crossover trial; in expt. 2, rats were fed diets supplemented or not with MRP model-systems. Intestinal microbiota composition in fecal (adolescents) or cecal (rat) samples was assessed by qPCR analysis. Negative correlations were found in the human assay between lactobacilli numbers and dietary advanced MRP (r = -0.418 and -0.387, for hydroxymethylfurfural and carboxymethyl-lysine respectively, p < 0.05), whereas bifidobacteria counts were negatively correlated with Amadori compounds intake. In the rat assay, total bacteria and lactobacilli were negatively correlated with MRP intake (r = -0.674,-0.675 and -0.676, for Amadori compounds, hydroxymethylfurfural and carboxymethyl-lysine respectively, p < 0.05), but no correlations were found with bifidobacteria., Conclusions: Dietary MRP are able to modulate in vivo the intestinal microbiota composition both in humans and in rats, and the specific effects are likely to be linked to the chemical structure and dietary amounts of the different browning compounds., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Published: 2014
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43. Structure, ligands and substrate coordination of the oxygen-evolving complex of photosystem II in the S2 state: a combined EPR and DFT study.

Author: Lohmiller T, Krewald V, Navarro MP, Retegan M, Rapatskiy L, Nowaczyk MM, Boussac A, Neese F, Lubitz W, Pantazis DA, and Cox N
Subjects: Ligands, Models, Molecular, Protein Conformation, Quantum Theory, Electron Spin Resonance Spectroscopy methods, Oxygen chemistry, Photosystem II Protein Complex chemistry
Abstract: The S2 state of the oxygen-evolving complex of photosystem II, which consists of a Mn4O5Ca cofactor, is EPR-active, typically displaying a multiline signal, which arises from a ground spin state of total spin ST = 1/2. The precise appearance of the signal varies amongst different photosynthetic species, preparation and solvent conditions/compositions. Over the past five years, using the model species Thermosynechococcus elongatus, we have examined modifications that induce changes in the multiline signal, i.e. Ca(2+)/Sr(2+)-substitution and the binding of ammonia, to ascertain how structural perturbations of the cluster are reflected in its magnetic/electronic properties. This refined analysis, which now includes high-field (W-band) data, demonstrates that the electronic structure of the S2 state is essentially invariant to these modifications. This assessment is based on spectroscopies that examine the metal centres themselves (EPR, (55)Mn-ENDOR) and their first coordination sphere ligands ((14)N/(15)N- and (17)O-ESEEM, -HYSCORE and -EDNMR). In addition, extended quantum mechanical models from broken-symmetry DFT now reproduce all EPR, (55)Mn and (14)N experimental magnetic observables, with the inclusion of second coordination sphere ligands being crucial for accurately describing the interaction of NH3 with the Mn tetramer. These results support a mechanism of multiline heterogeneity reported for species differences and the effect of methanol [Biochim. Biophys. Acta, Bioenerg., 2011, 1807, 829], involving small changes in the magnetic connectivity of the solvent accessible outer MnA4 to the cuboidal unit Mn3O3Ca, resulting in predictable changes of the measured effective (55)Mn hyperfine tensors. Sr(2+) and NH3 replacement both affect the observed (17)O-EDNMR signal envelope supporting the assignment of O5 as the exchangeable μ-oxo bridge and it acting as the first site of substrate inclusion.
Published: 2014
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44. An advanced glycation end product (AGE)-rich diet promotes Nε-carboxymethyl-lysine accumulation in the cardiac tissue and tendons of rats.

Author: Roncero-Ramos I, Niquet-Léridon C, Strauch C, Monnier VM, Tessier FJ, Navarro MP, and Delgado-Andrade C
Subjects: Animals, Female, Glucose chemistry, Glucose metabolism, Humans, Lysine chemistry, Lysine metabolism, Male, Rats, Rats, Wistar, Glycation End Products, Advanced metabolism, Lysine analogs & derivatives, Myocardium metabolism, Tendons metabolism
Abstract: The purpose of this study was to investigate the intake, excretion, and tissue accumulation of carboxymethyl-lysine (CML), after feeding rats a diet containing advanced glycation end products (AGEs) from a glucose-lysine (GL) model system. Rats were distributed into two groups and assigned to a control diet or a diet including 3% heated GL (GL diet) for three months. Feces and urine were collected over the last week. After sacrifice, serum was obtained and some organs were removed for CML analysis. The percentage of fecal CML was 2.5-fold higher in the animals fed the GL diet (33.2 vs 76.5% for control and GL group), whereby total recovery was 91.8% compared with a level of 54.6% in the animals fed the control chow, evidencing the importance of the chemical form and the net quantity of dietary CML on its elimination. We suggest that dietary dicarbonyl compounds from GL diet or dietary CML itself are responsible for CML accumulation in hearts and tendons. The most significant result of the present study is that the regular consumption of dietary AGEs in healthy individuals promotes CML accumulation in some organs.
Published: 2014
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45. Effects of model Maillard compounds on bone characteristics and functionality.

Author: Roncero-Ramos I, Delgado-Andrade C, Rufián-Henares JÁ, Carballo J, and Navarro MP
Subjects: Animals, Arginine analogs & derivatives, Arginine chemistry, Arginine metabolism, Biomarkers, Biomechanical Phenomena, Bone Resorption chemically induced, Bone and Bones chemistry, Bone and Bones physiology, Collagen Type I metabolism, Female, Lysine analogs & derivatives, Lysine metabolism, Rats, Rats, Wistar, Bone and Bones drug effects, Glucose chemistry, Glycation End Products, Advanced pharmacology, Lysine chemistry, Maillard Reaction
Abstract: Background: Physical and biomechanical properties of bone can be affected by non-enzymatic crosslinks, which are implicated in bone pathologies such as osteoporosis. The purpose of this study was to analyse the effects of the consumption of model Maillard reaction product (MRP) from glucose-lysine heated for 90 min at 150 °C (GL90) on bone composition and features. Rats were fed either a control diet or a diet containing 30 g kg(-1) GL90 for 88 days. Food consumption and the animals' body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for analysis of their composition and physical and biomechanical properties., Results: The organic matrix of the femur and the density of the pelvic bone decreased after MRP intake, whereas pentosidine content increased greatly with respect to the control group (41.7 ± 9.9 vs 171.4 ± 3.3 mmol mol(-1) collagen). The rising level of C-telopeptide degradation products from type I collagen (β-CTX) suggested a possible situation of increased bone resorption and/or higher turnover., Conclusion: In conjunction, the detrimental effect on the organic matrix, the situation of higher resorption and/or bone turnover indicated by the β-CTX values and the high pentosidine content in bone provoked negative consequences on certain mechanical properties such as the ability to withstand force and absorb energy without failure., (© 2013 Society of Chemical Industry.)
Published: 2013
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46. Effects of diets supplemented with MRPs from bread crust on the food intake and body weights in rats.

Author: Delgado-Andrade C, Roncero-Ramos I, Haro A, Morales FJ, Seiquer I, and Navarro MP
Subjects: Animal Feed analysis, Animals, Feces chemistry, Models, Animal, Molecular Weight, Rats, Rats, Wistar, Triticum metabolism, Body Weight, Bread analysis, Dietary Supplements analysis, Eating, Maillard Reaction, Triticum chemistry
Abstract: Traditionally the effects of dietary Maillard reaction products (MRPs) on food intake and body weight have been described in different studies, but few investigations have been conducted to analyse the main contributors responsible. We studied the effects of long-term consumption of MRPs from bread crust (BC) on rat growth, investigating the efficiency of diet and protein utilization. Different soluble and insoluble fractions of BC were studied to analyse the possible contributors. Additionally, the colour of the faecal material and the amount of fluorescent MRPs in the urine were measured in order to demonstrate MRP excretion. Six groups of rats were fed the following diets for 88 days: control (AIN-93G diet); bread dough (BD) and BC (containing 10% of BD or BC, respectively); low and high molecular weight (LMW-HMW) (containing soluble compounds from BC with <5 kDa and >5 kDa, respectively); insoluble (containing insoluble compounds from BC). Dietary MRPs tended to reduce the food intake and body weight significantly after consumption of more complex compounds (HMW and insoluble). The L*-value in the faeces decreased in animals fed BC and its derivatives, providing evidence of the presence of MRPs. The fluorescence associated with MRP excretion in urine was higher when the LMW diet was consumed, suggesting the easier absorption and clearance of the smaller compounds of BC.
Published: 2013
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47. Metabolic transit of N(ε)-carboxymethyl-lysine after consumption of AGEs from bread crust.

Author: Roncero-Ramos I, Delgado-Andrade C, Tessier FJ, Niquet-Léridon C, Strauch C, Monnier VM, and Navarro MP
Subjects: Animal Feed analysis, Animals, Bone and Bones metabolism, Feces chemistry, Female, Glycation End Products, Advanced blood, Glycation End Products, Advanced urine, Lysine blood, Lysine metabolism, Lysine urine, Male, Rats, Rats, Wistar, Bread analysis, Glycation End Products, Advanced metabolism, Lysine analogs & derivatives
Abstract: Our aim was to investigate carboxymethyl-lysine (CML) intake and excretion after feeding rats with diets containing advanced glycation end-products (AGEs) from bread crust (BC) or its soluble or insoluble fractions, and to identify the factors responsible for the effects observed. CML in serum and different tissues was measured to detect possible accumulations. For 88 days, weanling rats were fed with either a control diet or one containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. In the last week of the assay, faeces and urine were collected daily and stored as a 1 week pool. After sacrifice, blood was drawn to obtain serum and some organs were removed. CML analysis was performed by HPLC/MS/MS in diets, faeces, urines, serum and tissues. Faecal excretion of CML was strongly influenced by dietary CML levels and represents the major route of excretion (i.e. 33.2%). However, the urinary elimination of CML was probably limited or saturated, especially when more complex compounds were present in the diet. BC consumption increased CML in the cardiac tissue (170 ± 18 vs. 97 ± 3 μmol per mol lysine for BC and control groups), which correlated with the CML intake. The levels of this AGE in bone were unaffected by the dietary treatment, but in tail tendons CML was greatly increased in the animals that consumed the BC diet (102 ± 13 vs. 51 ± 8 μmol per mol lysine for BC and control groups, P = 0.006), which was associated with the intake of soluble LMW compounds present in BC. Despite the CML accumulation detected in different tissues, serum levels of protein-bound CML were unchanged, indicating the importance of measuring the free CML in this fluid as a real index of dietary CML.
Published: 2013
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48. Effects of dietary bread crust Maillard reaction products on calcium and bone metabolism in rats.

Author: Roncero-Ramos I, Delgado-Andrade C, Haro A, Ruiz-Roca B, Morales FJ, and Navarro MP
Subjects: Animals, Biological Availability, Body Weight, Calcium pharmacokinetics, Diet, Eating, Femur metabolism, Glycation End Products, Advanced metabolism, Molecular Weight, Rats, Rats, Wistar, Solubility, Tissue Distribution, Bone and Bones metabolism, Bread, Calcium metabolism, Calcium, Dietary pharmacokinetics, Maillard Reaction
Abstract: Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.
Published: 2013
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49. Influence of Maillard products from bread crust on magnesium bioavailability in rats.

Author: Roncero-Ramos I, Delgado-Andrade C, Morales FJ, and Navarro MP
Subjects: Animal Feed, Animals, Biological Availability, Diet, Random Allocation, Rats, Bread analysis, Magnesium pharmacokinetics, Maillard Reaction
Abstract: Background: Consumption of Maillard reaction products (MRPs) present in food has been related to deterioration of protein digestibility and changes in mineral bioavailability. We aimed to investigate the effects of MRP intake from bread crust on magnesium balance and tissue distribution, seeking causative factors among its different components., Results: During the final stage of the trial, magnesium digestibility improved by around 15% in rats fed diets containing bread crust or its derivatives compared with the control diet. Despite certain enhancements in magnesium bioavailability in this stage, for the experimental period as a whole, this parameter remained unchanged. However, specific changes in the content and/or concentration in some organs were observed, particularly in the femur, where magnesium levels were higher due to the smaller size of the bones., Conclusions: Consumption of MRPs from bread crust or its different components did not modify the magnesium balance. Nevertheless, the bread crust fractions led to some changes in magnesium tissue distribution which did not match the effects induced by complete bread crust intake, suggesting the importance of designing studies with real-food systems, in order to reinforce the validity of the findings obtained., (© 2012 Society of Chemical Industry.)
Published: 2013
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50. Composition and functionality of bone affected by dietary glycated compounds.

Author: Delgado-Andrade C, Roncero-Ramos I, Carballo J, Rufián-Henares J, Seiquer I, and Navarro MP
Subjects: Animals, Bone Density, Bread adverse effects, Female, Femur chemistry, Femur growth & development, Glycation End Products, Advanced chemistry, Glycation End Products, Advanced metabolism, Humans, Maillard Reaction, Pelvic Bones chemistry, Pelvic Bones growth & development, Rats, Rats, Wistar, Tibia chemistry, Tibia growth & development, Animal Feed analysis, Bread analysis, Femur physiology, Glycation End Products, Advanced adverse effects, Pelvic Bones physiology, Tibia physiology
Abstract: Our aim was to investigate the effects of Maillard reaction products (MRPs) from bread crust (BC) on bone composition and its mechanical properties, determining whether any such effects are related to the molecular weight of different MRPs. For 88 days after weaning rats were fed a control diet or diets containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. Animals' food consumption and body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for composition, physical and biomechanical properties analysis. It was found that body and femur weights, density, volume and organic matrix decreased, whereas pentosidine increased after consumption of experimental diets, especially in the HMW and insoluble groups (104.7 and 102.9 mmol mol(-1) collagen) vs. the control group (41.7 mmol mol(-1) collagen). Bone stiffness fell by 50% in the LMW, HMW and insoluble groups and failure load and energy to failure tended to decrease in the same animals after MRPs intake. Consumption of diets containing assayed MRPs during growth leads to lower bone size and introduces some changes in its mechanical behavior which appear to be related to an increase in the pentosidine level of bone.
Published: 2013
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