Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

Association between Vaccination Status and Mortality among Intubated Patients with COVID-19-Related Acute Respiratory Distress Syndrome

Importance: Although vaccination substantially reduces the risk of severe COVID-19, it is yet unknown whether vaccinated patients who develop COVID-19 and require invasive mechanical ventilation have lower mortality than controls. Objective: To examine the association between COVID-19 vaccination status and mortality among critically ill patients who require invasive mechanical ventilation owing to acute respiratory distress syndrome (ARDS) related to COVID-19. Design, Setting, and Participants: This multicenter cohort study was performed between June 7, 2021, and February 1, 2022, among 265 consecutive adult patients with COVID-19 in academic intensive care units who underwent invasive mechanical ventilation owing to ARDS. Exposures: Patients in the full vaccination group had completed the primary COVID-19 vaccination series more than 14 days but less than 5 months prior to intubation. This time threshold was chosen because guidelines from the US Centers for Disease Control and Prevention recommend a booster dose beyond that time. The remaining patients (ie, those who were unvaccinated, partially vaccinated, or fully vaccinated 5 months before intubation) comprised the control group. Main Outcomes and Measures: The primary outcome was time from intubation to all-cause intensive care unit mortality. A Cox proportional hazards regression model including vaccination status, age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation was used. Results: A total of 265 intubated patients (170 men [64.2%]; median age, 66.0 years [IQR, 58.0-76.0 years]; 26 [9.8%] in the full vaccination group) were included in the study. A total of 20 patients (76.9%) in the full vaccination group received the BNT162b2 vaccine, and the remaining 6 (23.1%) received the ChAdOx1 nCoV-19 vaccine. Patients in the full vaccination group were older (median age, 72.5 years [IQR, 62.8-80.0 years] vs 66.0 years [IQR, 57.0-75.0 years]) and more likely to have comorbid conditions (24 of 26 [92.3%] vs 160 of 239 [66.9%]), including malignant neoplasm (6 of 26 [23.1%] vs 18 of 239 [7.5%]), than those in the control group. Full vaccination status was significantly associated with lower mortality compared with controls (16 of 26 patients [61.5%] died in the full vaccination group vs 163 of 239 [68.2%] in the control group; hazard ratio, 0.55 [95% CI, 0.32-0.94]; P =.03). Conclusions and Relevance: In this cohort study, full vaccination status was associated with lower mortality compared with controls, which suggests that vaccination might be beneficial even among patients who were intubated owing to COVID-19-related ARDS. These results may inform discussions with families about prognosis.. © 2023 Wolters Kluwer Medknow Publications. All rights reserved

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

Background: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. Methods: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin &gt;4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. Results: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. Conclusion: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS. © 2021 The Author(s). Published by S. Karger AG, Basel

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study

Background: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). Conclusion: Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. © 2019, The Author(s)

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study (Intensive Care Medicine, (2021), 47, 2, (160-169), 10.1007/s00134-020-06234-9)

1832The original version of this article unfortunately contained a mistake. The members of the ESICM Trials Group Collaborators were not shown in the article but only in the ESM. The full list of collaborators is shown below. The original article has been corrected.openopenLabeau S.O.; Afonso E.; Benbenishty J.; Blackwood B.; Boulanger C.; Brett S.J.; Calvino-Gunther S.; Chaboyer W.; Coyer F.; Deschepper M.; Francois G.; Honore P.M.; Jankovic R.; Khanna A.K.; Llaurado-Serra M.; Lin F.; Rose L.; Rubulotta F.; Saager L.; Williams G.; Blot S.I.; Muzha D.; Ribas A.M.; Lipovesty F.; Loudet C.; Eller P.; Mostafa N.; Honore P.M.; Telleria V.M.; Smajic J.; Nogueira P.C.; Nafees K.M.K.; Hentchoya R.; Soledad J.; Cardenas Y.; Reyes A.G.; Sustic A.; Mpouzika M.; Vymazal T.; Jensen H.I.; Aguirre-Bermeo H.; Maddison L.; Valta M.; Bloos F.; Adipa F.E.; Koulouras V.; Enamorado J.; Agoston Z.; Birgisdottir H.; Gupta A.; Gurjar M.; Kilapong B.; Hashemian S.M.; Martin-Loeches I.; Cortegiani A.; Fletcher K.; Hayashi Y.; Waweru-Siika W.; Abidi K.; Lee S.-M.; Hadri B.; Dolgusevs M.; Abillama F.F.; Jovaisa T.; Thix C.; Elhadi M.; Nor B.M.; Ratnam S.; Mazlan M.Z.; Maiyalagan S.; Sanchez-Hurtado L.; Belii A.; Naranpurev M.; Gautam P.; 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Zakalik G.; Pagella G.; Baini M.; Campos P.A.; Sabbag I.; Schmukler A.; Fonseca I.P.; Alvarez G.M.; Ramirez M.; Tapia F.; Bascary C.A.; del Valle Gimenez G.; Bertoletti F.P.; Milioto E.; Bonsignore P.J.M.; Fernandez M.A.; Smith J.; Chimunda T.; Thompson L.; Maguire T.; Watts S.; Mitchell M.; Powell M.; Lye I.; Parsons L.; Baker N.; Reynolds C.; Thompson A.; Masters K.; Sosnowski K.; Morrison L.; Leslie G.D.; Lakshmanan R.; Tabah A.; Brown W.; McDowell-Skaines S.; McLucas A.; Smith C.; Tallot M.; Jones S.; Barakat-Johnson M.; Leong T.; Butcher R.; Martin K.; Douschan P.; von Lewinski D.; Eller P.; Schmutz R.; Kolussi U.; Salman F.; Ateya Z.; Mostafa N.; De Decker K.; Van Regenmortel N.; Jans A.; Wijnands P.; Coremans S.; De Bels D.; Depuydt T.; Paillet C.; Jacquet L.-M.; Swinnen W.; Hannes F.; Mergeay M.; Van de Velde S.; Allaert S.; Hoste P.; Borin C.; Balon S.; Fraipont V.; Biston P.; De Schryver N.; Dugernier T.; Van Cotthem I.; Telleria V.M.; Smajic J.; de Almeida A.O.; Jorge S.A.; Becker D.; Schmidt R.C.; Oliveira E.; Ramalho A.; Mazocoli E.; Fioretti A.; Barros E.; Serpa L.; Bianchini S.; Campanili T.; Pantaleao T.; Garcia P.C.; Ronchini A.L.V.; Santos R.; Nafees K.M.K.; Manap N.B.A.; Hentchoya R.; Bagshaw S.; Carney D.; Bagshaw S.; Davidow J.; Bagshaw S.; Rokosh E.; Bagshaw S.; Laizner A.M.; Smith S.; McQuirter M.; Kampayana B.S.; Favre R.; Sills M.; Laizner A.M.; Dallaire J.; Laizner A.M.; Becker C.; Microys S.; Bowes B.; Lajeunesse J.; Ghosh R.; Baptiste-Savoie J.; Raizman R.; Bagshaw S.; Suen G.; Taghavi N.; Smith O.; Fielding C.; Canales J.; Molina P.; Chaparro J.; Sepulveda M.I.; Zamorano M.J.F.; Rocha P.; Villanueva X.; Araya P.; Dayan M.; Avalos F.; Li X.; Liu Y.; Li X.; Chen X.; Jiang Z.; Yang J.; Chen J.; Yang L.; Wang K.; Gao J.; Fang X.; Zhao R.; Xia X.; Liu H.; Li J.; Wang H.; Meng G.; Di Y.; Wang D.; Zhao R.H.; Hu L.P.; Fang X.; Peipei X.; Jiao Q.F.; Wang H.Y.; Xia C.J.; Liu Y.; Ye M.; Wan Y.; Wang W.; Ding Y.; Ren A.; Gao Y.; Li Q.; Du G.; Yang J.; Shen Y.; Ding Y.; Li N.; Yuan C.; Li J.; Tan L.; Lin Q.; Guo H.; Yan H.; Xu X.; Zhang W.; Liang J.; Zhang L.; Tian E.; Zhao Q.; InSu L.; Dong J.; Gu Y.; Liu Y.; Zhao L.; Wang W.; Qiao H.; Tuo L.; Lv M.; Zhu J.Y.; Zhu J.F.; Wei Y.; Liu M.; He Y.; Cheng J.; Liu J.; Jia N.; Wei D.; Li Q.; Wu X.; Duan H.; Lin D.; Liang Q.; Luo X.; Xiong Y.; Huang R.F.; Fu J.; Zan T.; Ye M.; Shi Z.; Long Y.; Lei Y.; Liu X.; Yumei C.; Wang L.L.; Zhang Y.; Xu Y.; Cheng; Zhijuan W.; Sun C.; Song J.H.; Wang Y.; Liu X.M.; Liu Y.; Yuan Y.; Huang Q.; Yang F.; Wu Y.; Luo X.; Bai X.; Zheng H.; Song M.; Sun Y.; Li Z.S.; Luo F.; Liu M.; Li L.C.; Li X.; Zhang G.; Xiao L.; Yu T.; Gao G.; Wei W.; Wang F.; Han T.; Li T.; Zeng Q.; Zeng J.M.; Long Y.; Pan F.; Wang J.; He G.; Chen H.; Zhang F.; Chao Y.; Chunhua G.; Yao X.; Bai D.; Liu L.; Xu X.; Wang Y.; Liang X.; Zhang N.; Li X.; Zhang A.; Chen X.; Hu X.C.; Zhang H.; Wang R.X.; Tak P.S.; Ho S.W.; Jiang Q.X.; Ding X.; Hong L.; Miao L.; Feng Z.; Huang L.P.; Wu J.; Wang Y.; Guo J.; Zhang B.; Ma C.; Han Y.; Liu C.; Ding M.; Luan L.; Zheng J.; Lv S.; Jiang S.; Cao W.; Xue X.; Li J.; Liu G.; Wang J.; Wei X.; Zhang W.; Jiang Y.; Yao Z.; Gao L.; Li J.; Zhao W.; Jiang M.; Hao J.; Zhang J.; Song C.; Chen F.; Wang S.; Hu L.; Cao D.; Liu Y.; Wan J.; Wang X.; Shao H.; Zhang Z.; Cui X.; Liu J.; Zhao L.; Li X.; Fan L.; Zhang L.; Yu M.; Li B.; Li C.; Liu L.; Liu X.L.; Chen W.; Li Y.; Zhigang Z.; Yuchen W.; Mu C.; Zhu G.; Yang F.; Bo Q.; Li L.; Chen M.; Jiang J.H.; Yin H.; Pang X.; Gong Y.Y.; Yang S.; Yan X.; Zheng X.; Lei D.H.; Lei L.; Guo Y.; Liu L.; Yu J.; Sun W.; Bi A.P.; Li W.; Wu Y.; Li J.; Ni D.; Li X.; Liu Y.; Wu Z.; Song B.; Chen J.; Fei Q.; Xiaoyan Y.; Ran Q.; Xixi L.; Jiao X.; Ji H.; Zhiping S.; Hong M.; Jianhong M.; Hao Y.; Yin L.; Wang Y.; Hui C.; Ju W.; Xia X.; Huo Y.; Wang Y.; Chen L.; Yan Y.; Zhao Q.; Chen H.; Bao G.; Cao Y.; Hong L.; Zhang H.; Zhang Y.; Xu L.; Guixiang J.; Li Y.; Zhao H.M.; Huang X.; Dai Z.; Jian Y.; Zhang H.; Tian Z.; Cao Z.Q.; Li M.; Liu Y.; Ouyang F.; Ma F.; Jin W.; Ge L.; Wu S.F.; Li J.; Yuan W.; Chen T.; Shi G.; Chen Z.; Liu K.; Lin X.; Yuemen L.; Lijuan S.; Tian X.F.; Wang S.; Feng Z.X.; Liu X.Z.; Dong Y.; Zhang J.; Bocui N.; Jiang Z.X.; Yang J.; Wang G.X.; Zhao Y.; Wu X.; Yang Q.; Hu R.L.; Li X.Q.; Yu Z.J.; Yao Y.; Deng X.; Xiao Y.; Xie Y.; Yang Y.; Yang H.; Zhou Y.; Li Z.; Xiao M.; Yang Y.X.; Tian Y.; Gama L.M.S.; Hernandez J.S.; Cardenas Y.; Caicedo N.; Marin J.; Ochoa M.-E.; Gomez M.; Rojas-Suarez J.; Gonzalez J.; Reyes A.J.G.; Chapeta E.; Orozco E.; Filipovic-Grcic I.; Vukovic A.; Pecenkovic S.; Suput A.; Sustic A.; Zivanovic-Posilovic G.; Bozena A.; Udiljak N.; Milic M.; Radivojevic R.C.; Mihaljevic S.; Matas M.; Tonkovic D.; Culjak H.; Herceg I.; Pavlisa G.; Dobric M.; Beker T.; Adam V.N.; Goranovic T.; Markoulias C.; Mathaios M.; Mylordou M.; Achilleos E.; Kleanthous P.; Kotanidi V.; Foka M.; Charalabous I.; Alexandrou A.; Georgiou M.; Patsalos A.; Zepoy S.; Constantinou C.; Piza P.; Vymazal T.; Wiborg E.; Bruhn L.; Kaasby K.; Pedersen K.R.; Mikkelsen S.; Collet M.; Langvad A.; Andresen H.; Fischer S.; Kjaergard I.E.; Jepsen B.; Husted B.; Bestle M.; Kodal A.M.; Hansen T.C.B.; Pedersen A.S.B.; Thomsen T.D.; Hoegenhaven A.; From M.; Frandsen T.M.; Henning G.; Hansen A.; Jensen H.I.; Bliksted I.A.; Tamayo L.M.; Mogrovejo P.; Aguirre-Bermeo H.; Palaez C.; Tutillo D.R.M.; Hurtado C.V.; Garcia M.F.; Alvarez D.; Guerrero F.; Vasquez A.; Kutimets M.; Tamme K.; Maddison L.; Anvelt E.; Dlamini-Sserumaga L.; Lofqvist C.; Lusenius V.; Kauppi O.; Sakki J.-K.; Tervo-Heikkinen T.; Kesti U.; Merilainen M.; Karjula E.; Peltomaa M.; Palmu A.; Ahtiala M.; Valta M.A.; Mentec H.; Plantefeve G.; Besch G.; Pili-Floury S.; Ledochowski S.; Deserts M.D.; Giacardi C.; Daubin C.; Massard A.; Le Guen Y.; Blanc A.; Mandaroux S.; Gunther S.C.; Avogadro P.; Radavidson A.; Turc J.; Jochmans S.; Quintard H.; Boyer L.; Bruel C.; Philippart F.; Montravers P.; Atchade E.; Flessel N.; Chinardet B.; Soulisse L.; Pillard C.; Ngo D.; Bongiorno B.; 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Lepida D.; Liarmakopoulou A.; Koulouras V.; Papathanakos G.; Oikonomou M.; Ioannides P.; Papadopoulos D.; Staikos I.; Stafylaraki M.; Raitsiou B.; Mandis K.; Ravani I.; Kourelea S.; Efthimiou A.; Thoma G.; Bakas A.; Psarulis K.; Anisoglou S.; Papageorgiou E.; Michailidou E.; Tholioti T.; Lavrentieva A.; Sourla E.; Spyropoulou A.; Pantelas N.; Stalika K.M.M.; Georgakas I.; Karathanou A.; Tsikriki S.; Dimoula A.; Kanakaki S.; Vakalos A.; Pagioulas K.; Enamorado J.E.; Nardai G.; Hawchar F.; Blondal A.; Rygvadottir B.; Jonasdottir R.J.; Birgisdottir H.; Shah B.; Kaushik S.; Tripathy S.; Singh M.; Agarwal S.; Gupta M.; Ahmad M.; Mangal K.; Bhargava V.; Kushare V.; Jha S.; Bhakhtiani L.; Gupta A.; Kamal M.; Gurjar M.; Baronia A.; Kilapong B.; Susanti A.; Lestari M.I.; Zulkifli Z.; Baskoro W.; Zand F.; Zarei F.; Mahmoodpoor A.; Heidari F.; Jafaraghaee F.; O'Shea A.; O'Shea F.; O'Donnell C.; Craig G.; Fitzpatrick G.; Dunne L.; Hastings J.; Marsh B.; Cody C.; Campbell E.; Doyle D.; Pacturanan M.; Sheehan C.; Carey A.; Carter C.; Mulvey R.; Finn D.O.C.R.; Motherway C.; Walsh A.; Kehoe J.; Delossantos S.; Lalor J.; O'Nuallain S.; Behan H.; McPherson S.; Corcoran A.; Gordon P.; Rooney G.; Levy D.; Azencot M.; Gurevich V.; Lavy A.; Bendelari V.; Marconi R.; Barone A.; Gatti C.; Giampaoletti A.; Borgognoni C.; Ghioldi D.M.; Raimondo A.; Castiglione G.; Bruno A.V.; Rubulotta G.; Mo A.; Corso A.; Girianni S.; Bruni A.; Garofalo E.; Maggiore S.M.; Di Risio A.; Calamai I.; Spina R.; Spadaro S.; Volta C.A.; Cotoia A.; Mirabella L.; Maulicino L.; Abregal G.; Donvito M.; D'Ambrosio P.; Binda F.; Adamina I.; Galazzi A.; Negro A.; Vaschetto R.; Capuzzi F.; Boschetto M.; Stivanello L.; Bonaccorso L.; Megna C.; Cortegiani A.; Iozzo P.; Rizzo A.; Scire G.; Taibi M.R.; Tranello F.P.; Manzo A.; Traina L.; Pastore B.; Quaini A.; Giusti G.D.; Montaldi G.; Piergentili F.; Mancini F.; Casaioli S.; Uccelli F.; Guarracino F.; Onelli A.; Di Gravio V.; Cossu M.; Matrona O.; Rocco M.; Alampi D.; Dellafiore F.; Ranalli F.; Bossolasco M.; Brizio E.; Migliorino P.; Cortellazi P.; Rosati M.; D'Ambrosio F.; Quagliotto C.; Roman-Pognuz E.; Peratoner A.; De Rosa S.; Martin M.A.; De Sanctis F.; Ciorba P.; Fletcher K.; Toppin P.; Harding-Goldson H.; Taito S.; Shime N.; Yamamoto R.; Kanda F.; Hirao A.; Egi M.; Noguchi A.; Hashimoto S.; Aya U.; Sakuramoto H.; Ohuchi A.; Kataoka J.; Maruyama K.; Nakayama I.; Nishime Y.; Fujimoto K.; Takahashi K.; Tsujimoto M.; Shimizu M.; Waweru-Siika W.; Tole E.; Correia M.C.; Kim J.H.; Park S.; Kim K.C.; Baek J.; Bae J.-M.; Park S.Y.; Park T.S.; Lee H.B.; Park S.Y.; Park J.; Yeon-Joo L.; Young-Jae C.; Lee S.-M.; Jeon K.; Kim S.C.; Lee J.; Chee H.K.; Huh J.W.; Sim Y.S.; Kim J.; Chang Y.; Ahn J.-J.; Kang B.J.; Lee W.-Y.; Lee S.J.; Hadri B.; Baftiu N.; Krastins I.; Dolgusevs M.; Abillama F.F.; Stiban S.; Feghaly M.E.; Gharios E.; Merheb M.; Benlamin M.; Khaled A.; Belkhair W.A.; Tabib M.; Ashour F.; Elhadi A.; Tababa O.W.E.; Khaled T.; Alkhumsi S.I.R.; Alshrif A.I.; Aboufray A.A.; Alabuzidi A.; Triki A.R.; Elgammudi M.; Zahra H.B.; Soula E.; Al-Alawi M.M.S.; Ahmed H.; Ghula M.A.A.; Vosylius S.; Mouton L.; Rastegar T.; Sertznig C.; Martin G.; Thix C.; Theisen C.; Ferretti C.; Gils F.; Gallion M.; Zainudin A.; Bahrin L.K.K.; Deva S.R.; Rahim A.H.A.; Wahab S.; Mazlan M.Z.; Hassan W.N.W.; Ismail W.N.W.; Ali M.N.; Khoo T.M.; Samat N.M.; Tong J.M.G.; Adib N.A.N.; Nor M.B.M.; Ratnam S.; Ismail N.; Ratnam S.; Sulaiman S.R.; Foong K.W.; Alias A.; Hua N.P.; Maiyalagan S.; Maiyalagan S.; Zermeno J.M.; Blanco D.; Duran K.; Nava C.L.L.; Nandyelly S.J.R.; Sanchez-Hurtado L.A.; Tejeda-Huezo B.; Del Moral Armengol M.; Nava L.P.A.; Herrera J.G.; de Anda G.F.V.; Gallegos-Perez H.; Hernandez-Sanchez N.; Hernandez-Ponce L.; Gorordo-Delsol L.; Hernandez-Romero M.; Gomez S.; Molinar F.; Namendys-Silva S.A.; Romero-Gonzalez J.P.; Gonzalez D.; Landaverde A.; Sosa M.A.; Navarro B.; de Molina Serrano J.I.R.; Iburrigarro S.R.; Ibarra A.; Aguirre J.; Martinez-Gonzalez M.; Padilla N.R.C.; Pineda A.A.V.; Villafuerte M.V.E.; Herrera M.O.G.; Belii A.; Naranpurev M.; Baasanjav B.; Hachimi A.; Elkhayari M.; Abidi K.; Dendane T.; Subedi N.B.; Pathak S.D.; Gautam P.; Manandhar M.; Van Gulik L.; Van Den Brink M.; Van Vliet P.; Gerretsen B.; Van Den Berg L.; De Haan M.; Tuinstra B.; Kuijpers P.; Reijntjens J.; Vermeijden J.W.; Rinket M.; Vanroest M.; Reidinga A.; Loef B.; Dieperink W.; Onrust M.; Dormans T.; Bormans L.; Koopmans M.; Gerritsen R.T.; Van Den Elst A.; Evers M.; Oiting O.; Wilting R.; Ramaker B.; van der Kuil M.; Fijen J.-W.; Haas L.; De Lange D.; Haringman J.; Newby L.; Parke R.; Gilder E.; Hacking D.; Dagooc R.; Song R.; Waibel H.; Dawn F.; Rapley J.; Chadwick L.; Chapman C.; Crone P.; Albrett J.; Marko P.; Goodson J.; Browne T.; Whitticase R.; Davidson C.; Judd H.; Owens D.; Onyeka T.; Ugwu I.; Ilesanmi R.; Adejumo P.O.; Owojuyigbe A.; Adenekan A.; Uba S.; Chime C.; Jibrin D.; Sankey B.J.; Adekola O.; Olanipekun S.; Olanipekun S.; Adekola O.; Shosolcheva M.; Gievski V.; Kartalov A.; Naumovski F.; Kuzmanovska B.; Trposak A.; Bogoevska-Miteva Z.; Rosalia R.; Olsen B.F.; Sjobo B.; Jensen K.D.; Sykehus D.; Johansen B.F.; Straede E.; Johansen E.; Finnstrom I.J.; Toellefsen A.; Ostenjo H.; Bjorgen H.; Bratsberg B.; Kristoffersen E.; Skorstad E.M.; Hansen S.; Vullum S.; Lunde G.A.; Arntsen W.; Lund M.; Akselsen G.R.; Monstad K.R.; Stenset A.; Haugom H.; Monsen B.; Hogvall L.; Trudvang S.; Galaaen B.; Malmin S.K.; Andersen M.H.; Hargott R.F.; Andersen Y.; Steffenak E.; Nyhus M.; Meland B.; Hashmi M.; Rivas N.; Maidana E.; de Jesus Ortiz A.; Cabral D.M.B.; Simi M.; Aponte C.; Rivas J.C.; Gill S.; Garcia A.; Alvarenga G.; Cespedes L.; Perez H.; Moreira M.L.; Canete F.; Gonzalez R.; Monges N.; Garcia A.; Coman M.; Pederzani M.; Franco N.; Aganon F.; Martinez R.; Noblezada-Uy D.; Ellazar C.G.; Cerezo F.D.; Hernandez A.M.; Palo J.E.; Aperocho C.A.J.; Isanan M.; Tubacka M.; Jasiewicz P.; Czuczwar M.; Borys M.; Gutysz-Wojnicka A.; Glinka L.; Gawda R.; Mikaszewska-Sokolewicz M.; Bilawicz J.; Cabrita P.; Vieira J.; Figueiredo M.F.; Pinheiro C.M.; Antunes N.; Pedro L.; Ferreira F.; Parente I.; Varela M.; Fernandes F.; Martins C.; Viveiros A.; Cavaco R.; Rita C.S.; Dias S.; Feranandes A.M.; Silva P.; Nunes C.; Cabral J.; Sousa B.; Pires F.; Ferreira H.; Santos J.; Pinto V.M.V.; Bispo B.M.; Ferreira A.; Molinos E.; Lafuente E.; Gregorio R.; Costa H.; Lima A.; Ferreira S.; Seromenho V.; Luis E.; Valerio I.; Cesar H.; Tavares A.; Alsheikhly A.S.; Mahmood S.; Guran C.T.; Moise A.; Filipescu D.C.; Luchian M.; Tomescu D.; Popescu M.; Scutariu M.A.; Petrisor C.; Hagau N.; Grigoras I.; Patrichi T.; Gusarev V.; Pivkina A.; Kulakov V.; Ignatenko O.; Kovaleva J.; Zhivotneva T.; Zhedaeva M.; Matiushkov N.; Ershova O.; Egorova N.; Khoronenko V.; Baskakov D.; Sergeev D.; Piradov M.; Grishina L.; Magomedov M.; Zuev E.; Gorokhovatsky U.; Leonova A.; Fadeeva L.; Belskiy V.; Galishevskiy D.; Zubareva N.; Tribulev M.; Zueva O.; Kiselev A.; Kamenshchikov N.; Tokareva E.; Petrushin M.; Starchenko I.; Twagirumugabe T.; Nshimyumuremyi I.; Muhizi J.; Buregeya E.; Nzarora J.; Assiri A.; Ebaid M.S.; Almekhlafi G.; Mandourah Y.; Velickovic J.; Velickovic D.; Jovanovic B.; Hadzibegovic A.; Stefanovic B.; Misic V.; Bumbasirevic V.; Rajkovic M.; Stojanovic M.; Gavrilovic S.; Stanojevic M.; Martonova A.; Yaghi A.; Turcan A.; Firment P.; Slobodianiuk G.; Rabarova D.; Lancaricova D.; Vlaovic J.; Groznik M.; Lukic M.; Perme J.; Sostaric M.; Umek N.; Mirkovic T.; Dolenc S.; Knafelj R.; Fister M.; Zorko N.; Markota A.; Yeni N.P.; Jali P.; Schmollgruber S.; Syed M.R.; Parag N.; Wise R.; Galiana M.; Navarro J.A.; De Pablo A.M.; Albert P.; Martinez P.; Mendiara Y.; Garcia B.; Llinas A.A.; Riveiro M.; Gallart E.; Riera A.; Sanz M.; Salo S.; Lajara M.A.G.; Nieto M.V.; Garcia R.; Pena J.M.G.; Gorgolas M.C.; Isasi M.A.; Sierra R.; Gordo F.; Conejo I.; Salva-Costa V.; Garzon-Tovar C.; Lospitao S.; Gonzalez R.; Gutierrez P.; Girona M.; Adamuz J.; Olivares P.G.; de Ceballos J.P.G.; Tirado C.; De Wit I.; Polo A.B.C.; del Mar Diaz Salcedo M.; Ripolles-Melchor J.; Martinez-Hurtado E.; Alvarez J.D.; Arcas M.L.B.; Gonzalez J.I.T.; de la Ventana A.B.S.; Calleja P.L.-A.; Alvarez R.G.; Zamora P.S.; Guerrero A.O.; Cosano R.; Perez-Vacas J.; Campos-Perez M.; Barreiro E.M.; Sanchez L.C.; Diaz M.G.; Jimenez R.; Del Rio Cabajo L.; Muriel D.S.; Alonso H.F.; Fernandez A.W.; Pinan I.S.; Albaiceta G.M.; Fernandez M.C.I.; Abos F.J.S.; Monedero P.; Chueca R.M.; Aguirre L.G.; Manosa S.C.; Luque C.P.; Calpe N.; Losilla M.R.; Fores M.T.; Farre O.; Fernandez O.; del Rosario Villar Redondo M.; Arteta Arteta D.S.; Sanchez M.A.H.; Espinosa C.P.; Reyes L.M.; Domenech L.C.; Guillen C.V.; Alvarez J.T.; del Cotillo M.; Barrueco-Francioni J.E.; Conde B.B.; Blanco M.P.S.; Blasco M.L.; Clement A.I.; Hurtado C.; Sanz L.C.; Perez-Torres D.; Prol-Silva E.; Pereira J.; Gonzalez I.A.; Cano A.E.; Nunez C.R.; Fernadez I.L.; Fernandez A.A.M.; Del Bosque Diez R.; Hilario B.; Zalba-Etayo B.; Pascual-Bielsa A.; Panka B.; Banwarie P.; Nahar D.; van Axel A.; Boedjawan N.N.; Jansson E.B.; Malvemyr A.-S.; Johansson L.; Sandberg U.; Tingsvik C.; Mattsson G.; Lof G.; Spangfors M.; Ringdal M.; Geijer S.; Orvelius L.; Hylen M.; Lagerhall C.; Joelsson-Alm E.; Akerman E.; Hellkvist V.H.; Mickelsson U.; Akerman E.; Wahlbom E.; Larsson I.-M.; Wallin E.; Boroli F.; Ory S.; Jong M.L.; Dullenkopf A.; Lang M.; Fleury Y.; Maus M.; Ben-Hamouda N.; Fishman A.; Hsu M.Y.; Chang S.C.; Trongtratul K.; Sawawiboon C.; Morakul S.; Khwannimit B.; Merritt-Charles L.; Singh K.; Ventour D.; Figaro-Barclay D.; Sankar-Maharaj S.; Mebazaa M.S.; Kamoun S.; Elatrous S.; Besbes L.; Abroug F.; Naija W.; Elhechmi Y.Z.; Sellami W.; Hajjej Z.; Merhabene T.; Talik I.; Kuscu O.O.; Dilek O.; Zerman A.; Dal H.C.; Turan S.; Aydemir S.; Yilmaz H.; Calili D.K.; Izdes S.; Cengiz M.; Gumus A.; Tasdemir B.; Kagnici A.; Ay M.; Ay S.A.; Caliskan G.; Akbas T.; Balbay A.O.; Efe S.; Inal V.; Elay G.; Karabacak P.; Ozserezli B.; Senturk E.; Demirkiran O.; Bozbay S.; Dikmen Y.; Erdogan E.; Akker M.; Peker N.; Ozgultekin A.; Serin S.O.; Turan C.; Karaoren G.; Goksu S.; Karakurt S.; Arikan H.; Gul F.; Cinel I.; Kara I.; Undar H.N.; Bayraktar Y.S.; Celik J.B.; Tokur M.E.; Aydin D.T.; Yildiz I.; Ozcan B.; Erdivanli B.; Erdivanli B.; Ozcan B.; Eroglu A.; Akdag D.; Unlu N.; Fielding M.; Dungca A.; Ali A.; Thankamma B.; Reyes P.E.; John S.; Rajendran A.; Ahmad F.K.E.; Smiley K.A.; Hojden S.; Miller M.T.; Das Sasidharan Nair V.; Antonio M.G.S.; Qawasmeh K.A.; Shawish S.A.; Twiggs H.; Rosado I.; Babych V.; Morren F.; Young C.; Vaughan-Jones N.; Harris S.; Burns K.; Georgiev C.; Shayamano R.; Kerslake I.; Creber P.; Vochin A.; O'Brien C.; Caddell P.; Hagan S.; Hughes M.; Torlinski T.; Sherwin J.; Kannan S.; Markham A.; Lebon R.; Cupitt J.; Cranshaw J.; White N.; Marriott V.; Milner W.; Groba C.B.; Azoia J.; Polgarova P.; George S.; Kapoor R.; Lynch C.; Fox N.; Cranmer K.; Fox N.; Llewellym T.; Matthews K.; Maltby L.; Ibao J.; Boulton K.; Jarman R.; Baxter K.; Raj A.S.; Moghal A.; White J.; Barrowcliffe S.; Pulletz M.; Ganeshalingam V.; Baruah R.; Baker H.; Woods J.; Ei P.P.; Ogbeide V.; Hayden P.; Matthews K.; Hughes J.; Balasubramanian M.; Salberg A.; Saha R.; Holmquist D.; Young C.; Derbyshire C.; Smith N.; Stones E.; Ademokun J.; Popescu M.; Legorburo M.S.; North S.; Brett C.; Jaundoo H.; Craig J.; Whiteley S.; Howcroft C.; Wilby L.; Delve P.; Shaw D.; Williams K.; Welters I.D.; McMullen J.; Brett S.; Flores L.; Trueman-Dawkins T.; Templeton M.; Adams J.; Smith C.; Prowle J.; Byers H.; McDonnell A.; Rose B.O.; Reece-Anthony R.; Mendes L.; Vizcaychipi M.; Bull R.; Lacaden G.; Santiago E.; Delgado C.C.; Farnell-Ward S.; Thorpe E.; Somerville J.; Williams A.; Cummings D.; Derrick H.; Brumwell S.; Randell C.; McCann N.; Aves E.; Berry G.; Szakmany T.; Gunter U.; Pulak P.; Sarkar N.; Wright K.; Gomes V.; Jones J.; Palfrey R.; Camsooksai J.; Lewis A.; Eneas A.; Tridente A.; Barr L.; Jovaisa T.; Thomas B.; Parkin E.; Horner D.; Frey C.; Bench S.; Baumber R.; Broadhurst P.; Jackson M.; Williams L.; Clark M.; Paddle J.; Bean S.; Buckley S.; Palfreeman C.; Liu S.; Allison N.; Attwood B.; Parsons P.; Houghton V.; Turner S.J.; Higgins D.; Bielskute E.; Horrigan N.; Jacob R.; Habgood K.; Zaki A.; Collins A.; Lord J.; Ramiro C.; Kubisz-Pudelko A.; Kotze M.; Williams H.; Iovenko I.; Tsarev A.; Zgrzheblovska L.; Briva A.; Mendez G.; Napolitano L.; Teig M.; Lee J.; Rodriguez G.E.; Ben-Jacob T.; Potestio C.; Eng T.; Mahanes D.; Khanna A.; Duggal A.;