Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

sTREM-1, sIL-2Ralpha, and IL-6, but not sCD163, might predict sepsis in polytrauma patients: a prospective cohort study

Contains fulltext : 174707.pdf (publisher's version ) (Closed access)BACKGROUND: To investigate whether sTREM-1, sIL-2Ralpha, sCD163, and IL-6 predict septic complications following polytrauma. Prospective observational study in a university hospital intensive care unit. METHODS: Blood samples were drawn on admission, 24 and 48 h after the injury from 64 adult polytrauma patients. The occurence of infectious complications was investigated. The sepsis-free rates for the multiple trauma patients were considered as end points in the Kaplan-Meier plot analysis. RESULTS: Upon admission, sIL-2Ralpha mean values were higher in the T group compared to the T&S patients (1789 +/- 1027 pg/mL versus 1280 +/- 605 pg/mL, p = 0.02). The initial mean values of sTREM-1, IL-6, and sCD163 did not discriminate between the T and T&S groups patients (p > 0.05). sTREM-1 cutoff was 62 pg/mL: the sepsis-free rates differed significantly between the patients with sTREM-1 concentrations lower and higher than the cutoff (80 versus 48 %, p /=1593 pg/mL, 86 % did not present sepsis; for sIL-2Ralpha values in the range 946-1593 pg/mL, the sepsis-free rate was 68 %, while from the patients with sIL-2Ralpha <945 pg/mL, only 40 % remained sepsis-free (p = 0.05). sCD163 cutoff of 1000 ng/mL did not discriminate between the patients (76 versus 64 %, p = 0.28). For IL-6, the sepsis-free rates differed significantly between the patients with concentrations lower and higher than 400 pg/mL (78 versus 38 %, p < 0.01). CONCLUSIONS: sTREM-1, sIL-2Ralpha, and IL-6, but not CD163, may be used as prognostic markers for the occurrence of sepsis in multiple trauma patients. LEVEL OF EVIDENCE: Level II-Diagnostic tests and criteria

The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases

Contains fulltext : 138726.pdf (publisher's version ) (Open Access)BackgroundThe extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers.MethodsThe release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n inverted question mark= inverted question mark11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn inverted question marks disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed.ResultsIn-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNF inverted question mark (rs inverted question mark= inverted question mark0.80, P inverted question mark< inverted question mark0.05), IL-6 (rs inverted question mark= inverted question mark0.65, P inverted question mark< inverted question mark0.05), and IL-1Ra (rs inverted question mark= inverted question mark0.57, P inverted question mark= inverted question mark0.06), and negatively with IL-10 (rs inverted question mark= inverted question mark-0.58, P inverted question mark= inverted question mark0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P inverted question mark= inverted question mark0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P inverted question mark= inverted question mark0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P inverted question mark< inverted question mark0.0001 for both].ConclusionssTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions

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

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 ( &gt;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 - &lt;= 50, 51-60, 61-70, 71-80, &gt;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 (&lt;= 50 = 25.2%: 51-60 = 30.3%; 61-70 = 32.8%; 71-80 = 30.7%; &gt;80 = 30.9%). Hospital mortality increased with age and in patients &gt;80 years was almost twice that of patients &lt;= 50 years (493% vs 25.2%, p &lt; .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age &gt; 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

Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP)

Purpose: To evaluate differences in the characteristics and outcomes of intensive care unit (ICU) patients over time. Methods: We reviewed all epidemiological data, including comorbidities, types and severity of organ failure, interventions, lengths of stay and outcome, for patients from the Sepsis Occurrence in Acutely ill Patients (SOAP) study, an observational study conducted in European intensive care units in 2002, and the Intensive Care Over Nations (ICON) audit, a survey of intensive care unit patients conducted in 2012. Results: We compared the 3147 patients from the SOAP study with the 4852 patients from the ICON audit admitted to intensive care units in the same countries as those in the SOAP study. The ICON patients were older (62.5 ± 17.0 vs. 60.6 ± 17.4 years) and had higher severity scores than the SOAP patients. The proportion of patients with sepsis at any time during the intensive care unit stay was slightly higher in the ICON study (31.9 vs. 29.6%, p = 0.03). In multilevel analysis, the adjusted odds of ICU mortality were significantly lower for ICON patients than for SOAP patients, particularly in patients with sepsis [OR 0.45 (0.35–0.59), p < 0.001]. Conclusions: Over the 10-year period between 2002 and 2012, the proportion of patients with sepsis admitted to European ICUs remained relatively stable, but the severity of disease increased. In multilevel analysis, the odds of ICU mortality were lower in our 2012 cohort compared to our 2002 cohort, particularly in patients with sepsis. © 2018, The Author(s)

Higher Fluid Balance Increases the Risk of Death from Sepsis: Results from a Large International Audit∗

Objectives: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. Design: Observational cohort study. Setting: Seven hundred and thirty ICUs in 84 countries. Patients: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. Measurements and Main Results: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. Conclusions: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death

age: Observational data from the ICON audit

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, Colomb