Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome

Abstract

Background

Abdominal infections are frequent causes of sepsis and septic shock in the intensive care unit (ICU) and are associated with adverse outcomes. We analyzed the characteristics, treatments and outcome of ICU patients with abdominal infections using data extracted from a one-day point prevalence study, the Extended Prevalence of Infection in the ICU (EPIC) II.

Methods

EPIC II included 13,796 adult patients from 1,265 ICUs in 75 countries. Infection was defined using the International Sepsis Forum criteria. Microbiological analyses were performed locally. Participating ICUs provided patient follow-up until hospital discharge or for 60 days.

Results

Of the 7,087 infected patients, 1,392 (19.6%) had an abdominal infection on the study day (60% male, mean age 62 ± 16 years, SAPS II score 39 ± 16, SOFA score 7.6 ± 4.6). Microbiological cultures were positive in 931 (67%) patients, most commonly Gram-negative bacteria (48.0%). Antibiotics were administered to 1366 (98.1%) patients. Patients who had been in the ICU for ≤2 days prior to the study day had more Escherichia coli, methicillin-sensitive Staphylococcus aureus and anaerobic isolates, and fewer enterococci than patients who had been in the ICU longer. ICU and hospital mortality rates were 29.4% and 36.3%, respectively. ICU mortality was higher in patients with abdominal infections than in those with other infections (29.4% vs. 24.4%, p < 0.001). In multivariable analysis, hematological malignancy, mechanical ventilation, cirrhosis, need for renal replacement therapy and SAPS II score were independently associated with increased mortality.

Conclusions

The characteristics, microbiology and antibiotic treatment of abdominal infections in critically ill patients are diverse. Mortality in patients with isolated abdominal infections was higher than in those who had other infections.

Background

Abdominal infection is a common indication for admission to the intensive care unit (ICU) and the abdomen is the second most common site of invasive infection among critically ill patients in epidemiological [1–3] and therapeutic [4] studies. Abdominal infections are more often associated with septic shock and acute kidney injury than are infections in other sites [5, 6]. The spectrum of disease and severity is broad and management of these infections is challenging [7–9].

Multicenter data on the clinical features and microbiology of abdominal infections in the critically ill are rare, and often limited to a single region or country. In recent years, an increase in abdominal infections due to nosocomial and resistant organisms has been reported [10–14], but large-scale data are lacking. Although outcomes may have improved over the years [15], abdominal infections still carry a significant mortality risk. Isolation of nosocomial microorganisms [16], enterococci [17] or fungi [18, 19] is often cited as contributing to mortality, but the extent to which these organisms contribute to that risk is unknown. The role of comorbidities as well as demographic characteristics has also not been studied on a large scale. Prolonged stay in a critical care environment may be associated with changes in microbiology, thus affecting empirical antibiotic treatment, yet recent guidelines do not include length of stay as a potential surrogate marker for the presence of nosocomial or less susceptible microorganisms [20].

The Extended Prevalence of Infection in the ICU (EPIC) II study was a large one-day point-prevalence study of infections in the ICU. The study showed that half of all ICU patients were infected on the study day and 71% were being treated with antibiotics [1]. We used the data collected in the EPIC II study to (1) analyze the characteristics of abdominal infections (patient characteristics, micro-organisms) as well as the antibiotics used to treat these infections; (2) explore the differences in microbiology according to the length of stay in the ICU; and (3) identify clinical and microbiological factors associated with mortality.

Methods

The EPIC II study was performed on May 8, 2007. Demographic, physiological, bacteriological and therapeutic data were collected from 13,796 adult (>18 years) patients in 1,265 participating ICUs from 75 countries (see Appendix for list of participating centers) on the study day as previously described [1]. The EPIC II study was approved by the Erasme Hospital ethics committee. Local ethical committee approval at each participating center was expedited or waived because of the purely observational nature of the study. Infection was defined according to the criteria of the International Sepsis Forum (ISF) [21] and classified by the attending physician. Microbiological analyses were performed locally. Participating ICUs were asked to provide patient follow-up until hospital discharge or for 60 days.

For the purposes of this study, we analyzed data from the patients who were diagnosed with an intra-abdominal infection.

Statistics

Statistical analyses were performed using PASW Statistics 18 for windows (SPSS Inc., Chicago, USA). Data are presented as mean (±standard deviation [SD]), median (interquartile range [IQR]), or number (%) as appropriate. To identify factors associated with mortality, a multivariable logistic regression model (single step, forced entry) was constructed using variables for which the P-value was <0.1 in univariable analysis. Goodness of fit was assessed by the Hosmer-Lemeshow statistic. All tests were two-tailed, and a P < 0.05 was considered statistically significant.

Results

Of the 7,087 infected patients, 1,392 (19.6%) were diagnosed as having an abdominal infection on the study day (Table 1). Cancer and chronic obstructive pulmonary disease (COPD) were the most frequent comorbidities. The majority of the patients (885 [63.7%]) had undergone emergency surgery. Other concomitant infections were frequently present, with respiratory infections and bloodstream infections occurring in 26.8% and 11.6% of the patients, respectively (Additional file 1: Table S1).

Table 1 Patient characteristics

Microbiological data were available for 931 patients (67%), with a total of 1,289 microorganisms isolated (Table 2). Polymicrobial infections were present in 40.1% of the patients. Escherichia coli was isolated most frequently, with Pseudomonas spp. and Klebsiella spp. ranking second and third among the Gram-negative isolates. Enterococcus was the most prevalent Gram-positive isolate. Antibiotic resistance was relatively rare: ampicillin-resistant enterococci were isolated in 70 patients (7.5%), methicillin-resistant staphylococci in 59 patients (6.3%). Candida species were isolated in 156 patients (16.8%), 75.6% of these isolates were Candida albicans.

Table 2 A total of 1289 micro-organisms were recovered from the 931 patients with abdominal infections and positive cultures

Almost all the patients with abdominal infections (98.1%) were receiving antibiotics: penicillins and other beta-lactam antibiotics (excluding cephalosporins) were used most frequently (38.6% and 34.4% of the patients, respectively) (Additional file 1: Table S2); 29.4% of the patients were receiving antifungal agents.

ICU (median 16 [IQR 6–34] days vs. 17 [7–34] days, P = 0.07) and hospital (30 [14–59] days vs. 29 [14–56] days, P = 0.68) lengths of stay (LOS) were similar in patients with abdominal infections and those with other infections. Overall ICU and hospital mortality rates were 29.4% and 36.3%, respectively (Table 1). Mortality rates were higher in patients who had abdominal infections than in patients from the EPIC II cohort who had other infections (ICU mortality 29.4% vs. 24.4%, P < 0.001, and hospital mortality 36.3% vs. 32.3%, P = 0.005). ICU and hospital mortality rates in non-infected patients in the EPIC-II cohort were 10.7% and 14.8%, respectively.

Non-survivors were older, had higher SAPS II and SOFA scores on the study day, and were more likely to have cirrhosis, heart failure, or hematological cancer. They were also more likely to be receiving mechanical ventilation or renal replacement than survivors (Table 3). Survivors and non-survivors had similar patterns of infecting organisms, except for P. aeruginosa and Stenotrophomonas maltophilia, which were isolated more frequently in non-survivors than in survivors (Additional file 1: Table S3). In multivariable analysis, hematological cancer, mechanical ventilation, cirrhosis, renal replacement therapy and SAPS II score on the study day were independently associated with increased mortality (Table 4).

Table 3 Characteristics of survivors and non-survivors

Table 4 Multivariable analysis with ICU mortality as the dependent variable

In patients who had been in the ICU for 2 days or less prior to the study day, there were more E. coli, methicillin-sensitive S. aureus and anaerobic isolates and fewer enterococci than in patients who had been in the ICU for a longer period of time; there was also a trend towards fewer P. aeruginosa, Citrobacter spp. and C. albicans isolates (Table 5).

Table 5 Microbiology and antibiotic use in patients who had been admitted for 2 days or less vs. more than 2 days on the study day

Discussion

This study is one of the first to look at abdominal infections in critically ill patients from a global perspective. The results show that abdominal infections are associated with significant mortality rates and that concomitant infections are frequent. Microbiology patterns and antibiotic treatments were diverse in this group of patients, and pathogens were different in patients who had been in the ICU for a longer period of time than in those more recently admitted. The severity of disease and presence of comorbidities determined outcome in these patients.

Mortality in patients who had abdominal infections was significantly higher than in patients who had other infections (most of which were respiratory infections), which was not found in previous studies. In an analysis of patients from the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, Volakli et al. reported no differences in mortality rates among patients with abdominal infections and those with respiratory infections [6]. The higher mortality rate in patients with abdominal infections in our study may be explained by a number of differences between abdominal and other infections. First, timely source control is particularly important in the management of abdominal infections [22], and the method by which source control is obtained may influence outcomes [23]. Failed source control is often difficult to identify and can be a cause of persistent infection. In addition, abdominal infections are typically polymicrobial and often associated with resistant organisms; in the current study, non-survivors more frequently had P. aeruginosa and Stenotrophomonas maltophilia as pathogens. Finally, the large number of concomitant infections may also have affected outcomes.

As expected, comorbidities, such as cirrhosis and hematological cancer, were associated with increased mortality, as was found in the EPIC II patients in general [1]. Most notably, the impact of cirrhosis was considerable with a 2.3-fold increase in the risk of death. A recent analysis of the Project Impact database also showed that cirrhosis was independently associated with an increased risk of 30-day mortality [24].

The microbiology patterns were diverse, and quite different from those in the overall EPIC II study population, in which staphylococci were isolated most frequently, and Gram-positive and Gram-negative organisms were equally present [1]. In the patients with abdominal infections, the picture was substantially different: Gram-negative bacteria were isolated almost twice as frequently as Gram-positive bacteria, with E. coli being the most prevalent pathogen; typical nosocomial microorganisms, such as P. aeruginosa and Enterobacter spp. were also frequently isolated. Indeed, P. aeruginosa was the second most frequently isolated Gram-negative microorganism, which may in part be due to the design of the study, but the percentages are comparable to other studies in this field [25]. Among the Gram-positive microorganisms, enterococci were most prevalent, whereas staphylococci were uncommon. Furthermore, there were important differences in microbiology between survivors and non-survivors, with P. aeruginosa and Stenotrophomonas maltophilia isolated twice and four times more often, respectively, in non-survivors than in survivors. These pathogens may have a greater degree of pathogenicity (although Stenotrophomonas is generally not considered to be a major pathogen), or may be more difficult to treat. Detailed data regarding antibiotic resistance, including information regarding resistance to specific antibiotics, were not collected so we are unable to comment further on these aspects.

The findings in this study suggest that physicians around the world seem to comply with international guidelines in this field as most patients receive broad-spectrum antibiotics, often in combination with agents aimed at fungi or even at resistant Gram-positive microorganisms. We also found that patients who had stayed in the ICU for 2 days or less on the study day had different characteristics to those who had been longer on the ICU. Microbiological isolates and antibiotic treatments were remarkably different between these groups with fewer carbapenems, glycopeptides and antifungals used in patients with shorter stays. Current guidelines for the selection of antibiotic therapy in critically ill patients do not mention length of stay in the hospital as a consideration for empirical treatment in patients with high-severity non-nosocomial infections. Nevertheless, this group represents a category of patients, presumably with community-acquired infection, who could potentially be treated with narrower spectrum antibiotics when local ecology allows. This hypothesis warrants further evaluation.

Fungal infections have received considerable attention in the last decade. Although the debate continues as to whether fungi are relevant in community-acquired disease, the situation is different in nosocomial infections and in severely ill patients [20]. Candida isolation has been identified as an independent predictor of mortality in some studies [19, 26, 27], which has triggered widespread use of empiric antifungal coverage with fluconazole in this setting. In the current study, fungi were isolated in approximately 1 in 6 patients, but antifungal therapy was administered to almost 30% of the patients, reflecting the high use of antifungal prophylaxis in this group. Fungi were found more often in patients who had been in the ICU for more than 2 days, but were not linked to mortality in the current study. Identifying which patients are at risk of fungal infection and may benefit from preemptive antifungal therapy remains a challenge; length of stay in the hospital and other risk factors for fungal infection, such as upper gastro-intestinal tract perforation and previous antibiotic exposure [28], should be considered before initiating antifungal therapy. The prevalence of Candida non-albicans isolates was lower than frequently reported in invasive candidiasis studies or other studies in patients with Candida peritonitis. For example, Montravers et al. reported that only 58% of patients with Candida peritonitis had C. albicans isolated from intraoperative cultures [18]. In patients with invasive candidiasis, a systematic review by Andes et al. indicated that just 44% of the isolates were C. albicans[29]; patients with Candida peritonitis accounted for only 1% of the patients in this review, however. It is not clear whether the infecting Candida species or its susceptibility plays a major role in determining outcome [18].

This study has a number of limitations. Because the study was not primarily focused on abdominal infections, the exact source and extent of infection were not recorded and the efficacy of source control and appropriateness of antimicrobial therapy could not be evaluated. The rate of superinfection and/or tertiary peritonitis could not be assessed. Data on the community-acquired versus nosocomial nature of infections were also not available and we, therefore, used the length of stay as a surrogate marker, but acknowledge that this has its limitations. Finally, as in all point-prevalence studies, patients who are admitted for a long period of time may skew the findings with more data collected on those who stay in the ICU for a longer period of time.

Conclusion

In conclusion, this study found that abdominal infections were present in about one fifth of ICU patients on the study day and concomitant infections were common. Microbiology patterns and choice of antibiotic therapy were diverse and differed in patients who had stayed in the ICU for 2 days or less compared to those with longer stays. Abdominal infections carry a poor prognosis, with higher mortality rates than in patients with infections from other sources. Disease severity, need for organ support and presence of comorbidities were independently associated with mortality in our cohort.

Appendix: List of participating centers by country, alphabetically

Andorra: Hospital Nostra Senyora de Meritxell (A Margarit); Argentina: Centro de Educación Médica E Investigaciones Clínicas (R Valentini); Clinica de Especialidades Villa Maria (AJ Zazu); Clínica Modelo de Morón (C Bevilacqua); Clinica Y Maternidad Suizo (M Curone); CMIC (R Rabuffetti); Hospital Aleman (P Comignani); Hospital Argerich (M Torres Boden); Hospital Britanico (F Chertcoff); Hospital Central de San Isidro (G Cardonatti); Hospital de Niños Dr. Héctor Quintana (F Adén); Hospital del Niño Jesús (L Marcos); Hospital Dr Pedro Ecay (M Dónofrio); Hospital Español de Mendoza (R Fernández); Hospital Español Medical Plaza (R Lamberghini); Hospital Internacional General de Agudos "José de San Matín" (S Balasini); Hospital Interzonal Dr. O. Alende (J Teves); Hospital Italiano de Buenos Aires (M Las Heras, J Sinner); Hospital Juan A. Fernández (D Ceraso); Hospital Municipal de Chivilcoy (D Curcio); Hospital Profesor Alejandro Posadas (L Aguilar); Hospital Provincial de Rosario (C Weller); Hospital Provincial del Centenario (L Cardonnet); Hospital Regional Rio Gallegos (R Santa Cruz); Hospital Regional Ushuaia (E Manrique); Hospital Universitario Austral (D Bernardez, T Iolster); Hospital Universitario Universidad Abierta Interamericana (G Chiappero); Instituto Privado del Quemado Med-Inter (D Curcio); Nuevo Hospital El Milagro (P Ramos); Ramos Mejia Hospital (J Vergara); Sanatorio Agote (I Moine); Sanatorio de la Trinidad Mitre (S Ilutovich); Sanatorio de Los Arcos (G Jannello); Sanatorio Dupuytren (M Waschbusch); Sanatorio Frangioli de Salud 2000 Srl (G Rios Picaza); Sanatorio Mater Dei (A Raimondi); Sanatorio Otamendi Y Miroli (M Miriam); Sanatorio Parque (L Carlos); Sanatorio San José (D Curcio); Armenia: Centro Gallego de Buenos Aires (M Caridi); Australia: Alfred Hospital (T Leong); Barwon Health (N Orford); Blacktown Hospital (G Reece); Box Hill Hospital (D Ernest); Cabrini Hospital (F Hawker); Concord Repatriation General Hospital (J Tan); Epworth Eastern Private Hospital (C Giannellis); Epworth Hospital Richmond (B Ihle); Flinders Medical Centre (A Bersten); Frankston Hospital (J McInnes); Gold Coast Hospital (M Tallott); John Hunter Hospital (B Mcfadyen); Joondalup Health Campus (J Vibert); Liverpool Hospital, Sydney South West Area Health Service (M Parr); Logan Hospital (K Tran); Mater Health Services (J Sutton); Mount Hospital (S Webb); Nambour General Hospital (N Groves); Nepean Hospital, NSW (L Cole); Prince Charles Hospital (D Long); Prince of Wales Hospital (F Bass); Princess Margaret Hospital For Children (S Erickson); Royal Brisbane and Womens' Hospital (J Lipman); Royal Children’s Hospital, Brisbane (D Long); Royal Children’s Hospital, Melbourne (C Delzoppo); Royal Darwin Hospital (J Thomas); Royal Perth Hospital (G Dobb); Royal Prince Alfred Hospital (M Daley); Sir Charles Gairdner Hospital (B Roberts); St John of God Hospital, Subiaco (S Webb); St Vincent’s Hospital, Melbourne (J Santamaria); Sydney Children’s Hospital (J Young); The Children’s Hospital at Westmead, Sydney (M Festa); The John Flynn Private Hospital (R Holland); The Prince Charles Hospital (D Mullany); The Queen Elizabeth Hospital (P Williams); The Townsville Hospital (M Corkeron); The Wollongong Hospital (M Gales); Westmead Hospital (A Banerjee); Women’s and Children’s Hospital, Adelaide (M Yung); Austria: University Hospital Innsbruck (N Mutz, M Hiesmayr); General Hospital (P Faybik); Hospital Hietzing (R Fitzgerald); Krankenhaus Barmherzige Brüder Linz (F Firlinger); Krankenhaus Der Barmherigen Brueder Wien (G Zasmeta); Krankenhaus Der Barmherzigen Brüder St. Veit (M Zink); Krankenhaus Der Barmherzigen Schwestern Linz (W Sieber); Krankenhaus Steyr (J Hildegard); Landeskrankenhaus Klagenfurt (R Bakondy); Landeskrankenhaus Stolzalpe (J Schlieber); Landeskrankenhaus Deutschlandsberg (G Filzwieser); Medical University Innsbruck (R Beer, M Joannidis); Medical University of Vienna (T Staudinger); Otto-Wagner Hospital (R Schuster); Unfallkrankenhaus Meidling Der Auva (W Scherzer); University Hospital (K Smolle); Wilhelminenspital (S Fitzal); Bangladesh: Central Hospital Limited (R Manzoor); Belgium: A.I.T. (J Brunain); Ambroise Paré (A Dive); Asz-Aalst (G Huylenbroeck); Az Groeninge Kortrijk (M Van der Schueren); Az Maria Middelares (H 't kindt); Az Sint Jozef Malle (E Slock); Az Sint Lucas (D Rijckaert); Az St Augustinus (J Raemaekers); Az St Jan Av (M Bourgeois); Az Vesalius (I Van Cotthem); Az Damiaan Oostende (G Nackaerts); C.H.N.D.R.F. (D Gusu); Centre Hospitalier de Mouscron (P Gadisseaux); CH Libramont (V Olivier); Chirec - Braine-L'Alleud (H Lignian); CHPLT Verviers (P Michel); CHR Citadelle (V Fraipont); CHR Haute Senne Soignies (M Van der Stappen); CHR St Joseph Mons-Warquignies (F Forêt); CHU Brugmann (D De Bels, J Devriendt, J Massaut); CHU Charleroi (P Biston); CHU Saint-Pierre (A Roman); CHU Sart Tilman, Liège (B Lambermont); Clinique Sainte Elisabeth (A De Meulder); Clinique Notre Dame (V Frederic); Clinique Notre-Dame de Grâce (T Sottiaux); Clinique Saint Luc, Bouge (P Ruyffelaere); Cliniques de L'Europe, St-Michel (V Collin); Cliniques de L'Europe, Ste Elisabeth (S Anane); Hôpital Francais (P Kleiren); Hôpital Saint-Joseph (M Simon); Hornu (S Machayekhi); Imeldaziekenhuis (E Frans); Institut Jules Bordet (G Leroy, T Berghmans); Jan Yperman Hospital (R Joseph); Olv Ter Linden Ziekenhuis, Knokke (J Eerens); Saint Luc University Hospital (PF Laterre); Sint Augustinus, Veurne (B Lagrou); St Vincent (R Rutsaert); St-Jozefkliniek Bornem-Willebroek (W Pisarek); UCL Mont-Godinne (A Dive); Universitair Ziekenhuis Gent (J De Waele); University Hospital Brussels (H Spapen); University Hospital of Liege (P Damas); Erasme University Hospital (JL Vincent); ZNA Stuivenberg (M Malbrain); Belize: Universal Health Services, Medical Center (J Hidalgo); Brazil: Bandeirantes Hospital (M Baptista); Barra Dor Hospital (D Salgado); Biocor Instituto (M Braga); Casa de Saude Sao Jose Caxias (C Avila); Centro Hospitalar Unimed (G Westphal); Centro Integrado de Atençaõ À Saúde -Unimed Vitória (E Caser); Clínica São Vicente da Gávea (A Alves); Complexo Hospitalar Santa Casa de Porto Alegre (G Friedman); Erasto Gaertner Hospital (M Luz); Federal University of Sao Paulo (M Assuncao); Fundacao Hospital de Clinicas Gaspar Vianna (H Reis); Fundação Hospitalar Do Estado de Minas Gerais - Fhemig (A Gomes); Fundação Pio Xii (U Silva); UNIFESP (W Nogueira Fh); Hopital das Clínicas - FMUSP (S El-Dash); Hospital Padre Albino-Faculdade de Medicina de Catanduva (J Valiatti); Hospital Alberto Cavalcanti (A Barbosa); Hospital Badim (C Coelho); Hospital Cardiotrauma Ipanema (M Knibel); Hospital Carlos Fernando Malzoni (C Minelli); Hospital Da Cidade de Passo Fundo (J Caovilla); Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (G Teixeira); Hospital das Clínicas, Universisty of São Paulo (A Hovnanian); Hospital das Nacoes (A Rea-Neto); Hospital de Base-Famerp (SL Lobo); Hospital de Clínicas Mario Lioni (M Lugarinho); Hospital de Clínicas Niterói (P Souza); Hospital de Doenças Tropicais de Goiânia (D Ferreira); Hospital do Cancer/Uopeccan (P Duarte); Hospital do Trabalhador (M Oliveira); Hospital dos Servidores do Estado Rio de Janeiro (J Marques); Hospital E Maternidade São José (R Machado); Hospital Estadual Diadema (P Rehder); Hospital Estadual do Grajau-Unisa (S Mataloun); Hospital Evangelico (M Grilo); Hospital Evangelico do Rio de Janeiro (P Quesado); Hospital Geral de Pedreira (M Moock); Hospital Geral de São Mateus (F Ferreira); Hospital Geral Roberto Santos (J Teles); Hospital Israelita Albert Einstein (E Silva); Hospital Israelita Albert Sabin (C Coelho); Hospital Júlia Kubitschek (A Morais); Hospital Mater Dei (F Carvalho); Hospital Memorial Arthur Ramos (M Wanderley); Hospital Meridional (M Velasco); Hospital Moinhos de Vento (N Brandão da Silva); Hospital Municipal São José (J Feijó); Hospital Nossa Senhora Da Salete (P Duarte); Hospital Pasteur (V Souza Dantas); Hospital Português (J Teles); Hospital Pró-Cardíaco (R Costa Filho); Hospital Quinta D'Or (A Japiassu); Hospital Regional Antônio Dias (D Villela); Hospital Regional de Barbacena (C Santos); Hospital Salvador (R Passos); Hospital Samaritano (R Alheira-Rocha); Hospital Santa Izabel (R Silva); Hospital Santa Paula (J Houly); Hospital Sao Cristovao (J Aldrighi); Hospital São Lucas (R Hatum); Hospital São Lucas da PUCRS (F Suparregui Dias); Hospital São Luiz - Unidade Itaim (L Ferreira); Hospital São Rafael (L Ferro); Hospital São Vicente de Paulo (J Gomez); Hospital Universitário Clementindo Fraga Filho - Ufrj (R Fleury); Hospital Universitario da Universidade Federal do Rio de Janeiro (C David); Hospital Universitário de Santa Maria (T Resener); Hospital Universitário do Oeste do Paraná (P Duarte); Hospital Universitário Lauro Wanderley - UTI Adulto (C Mendes); Hospital Universitario Regional de Maringa (A Germano); Hospital Vita Curitiba (M Oliveira); Hospital Vivalle (F De marco); Instituto de Espquisa Clinica Evandro Chagas (A Japiassu); Instituto Do Coração - HC-FMUSP (S Lage); Instituto Nacional de Cancer (J Salluh); Irmandade Santa Casa de Misericordia de Porto Alegre (A Torelly); Luxemburgo Hospital (R Sad); Mternidade Odete Valadares (A Barbosa); Prontocor Lagoa (G Oliveira); Samaritano Hospital (R Lima); Santa Casa Da Misericórdia de São João del Rei (J Paranhos); Santa Casa de Misericordia de Passos (M Oliveira); Santa Casa de Porto Alegre (M Rocha); São Sebastião Hospital (W Bitencourt); Universidade Federal Do Parana (A Rea-Neto); University of Londrina (C Grion); University of Sao Paulo (D Forte); Uti Da Disciplina de Clínica Médica-Unifesp (H Guimarães); Vitória Apart Hospital (C Piras); Bulgaria: Mbal Ruse (L Stephanova); Multiprofile Hospital of Active Treatment, Ruse (L Lyubenov); Uh St. Ekaterina (G Tsarianski); Univerisity Hospital (G Dimov); Canada: Capital Health-Queen Elizabeth II Health Sciences Centre (R Green); Centre Hospitalier Régional de Lanaudière (J Levasseur); Children’s Hospital of Eastern Ontario (R Ward); CHU Sherbrooke (O Lesur); Hôpital Charles Lemoyne (G Poirier); Mount Sinai Hospital (R Wax); Royal Jubilee Hospital (G Wood); St. Joseph’s Healthcare (D Cook); St. Michael’s Hospital (J Marshall); Toronto General Hospital (M Herridge); Toronto Western Hospital (N Ferguson); Victoria General Hospital (G Wood); Chile: Clinica Alemana de Santiago (M Espinoza); Clinica las Condes (S Valdés jimenez); Hospital Clínico de la Pontificia Universidad Católica de Chile (A Bruhn); Hospital del Trabajador (J Micolich); Hospital Dr G. Fricke (S Galvez); Hospital El Pino (I Escamilla Leon); China: Beijing Chaoyang Hospital (Q Zhan); Beijing Tongren Hospital (Y Xu); Chinense Pla General Hospital (Y Zhao); Fuxing Hospital, Capital Medical University (L Zhang); Guangdong Provincial People’s Hospital (T Qin); Peking Union Medical College Hospital (B Du); Peking University People’s Hospital (M Li); Ren Ji Hospital,Shanghai Jiao Tong University (X Wang); The Affiliated Hospital of Ningxia Medical College of China (Y Jing); The First Affiliate Hospital of China Medical University (Z Zhang); The First Affiliated Hospital of Dalian Medical University (W Xianyao); The First People’s Hospital of Nantong, Jiangsu (F Li); Zhong-Da Hospital and School of Clinical Medicine, Southeast University (Y Congshan); Colombia: Clinica General del Norte (C Rebolledo); Clinica Central del Quindio (D Diaz); Clinica Medellin (R Murillo Arboleda); Clinica Saludcoop (C Rebolledo); Clinica Santa Isabel de Valledupar. (A Arias Antun); Fundación Hospital San Carlos (G Montenegro); Fundacion Valle del Lili (M Granados); Hospital Bocagrande de Cartagena (C Duenas); Hospital Departamental de Villavicencio (N Perez); Hospital El Tunal (G Libreros Duque); Hospital San Jose de Bogota (M Coral); Hospital Santa Clara (G Ortiz); Costa Rica: Hospital Calderón Guardia CCSS (D Rodriguez); Croatia: Hospital for Infectious Diseases (B Barsic); Sveti Duh General Hospital, School of Medicine, Zagreb (M Cubrilo-Turek); University Hospital Centre (I Gornik); University Hospital Zagreb (M Grljusic); Cuba: Hospital Universitario Arnaldo Milian Castro (A Caballero lopez); Hospital Universitario Dr. Gustavo Aldereguía Lima (M Iraola ferrer); Czech Republic: Centre of Cardivascular and Transplant Surgery (P Pavlik); Charles University Teaching Hospital, Hradec Kralove (J Manak); Charles University Medical School and Teaching Hospital (J Radej); Faculty General Hospital, Charles University Prague (J Belohlavek); Faculty Hospital Brno (P Sevcik); Faculty Hospital Olomouc (L Blahut); General Teaching Hospital of 1St Faculty and Charles University (D Tyl); Horovice Hospital (J Steinbach); Klaudians Hospital (I Herold); Krajska Nemocnice Liberec (I Zykova); Nemocnice V Usti Nad Orlici (D Prchal); St. Anne’s University Hospital Brno (T Bartosik); University Hospital Brno (M Kolarova); University Hospital Olomouc (R Hájek, J Kohoutová, O Marek); University Hospital Ostrava (P Hon); University Hospital Plzen (I Chytra); Denmark: Århus University Hospital (H Betsch); Næstved Hospital (B Fogh); Rigshospitalet (K Espersen); Sygehus Fyn (K Jacobsen); Vejle Sygehus (P Berezowicz); Ecuador: Carlos Andrade Marín Hospital (F Guerrero); Clinica La Merced (E Salgado); Hospital Eugenio Espejo (D Barahona); Hospital General de Las Fuerzas Armadas del Ecuador Hg-1 (H Del pozo sanchez); Hospital Metropolitano (M Jibaja); Egypt: Dar Alfouad Hospital (A Alansary); Estonia: East Tallinn Central Hospital (A Reintam); Tartu University Hospital (J Starkopf); Finland: Helsinki University Central Hospital (V Harjola); France: AP-HP, CHU Jean Verdier (L Tual); Assistance Publique-Hôpitaux de Marseille, CHU Nord (M Leone); Centre Hospitalier Dunkerque (M Serge); Centre Hospitalier Universitaire (P Michel); Centre Hospitalier (O Leroy); Centre Hospitalier D'Auch (L Mallet); Centre Hospitalier de Blois (B Marc); Centre Hospitalier de Fougères (D Dormoy); Centre Hospitalier de Niort (H Pascal); Centre Hospitalier Dr Schaffner (L Tronchon); Centre Hospitalier du Pays D'Aix (B Garrigues); Centre Hospitalier Region Annecy (C Santré); Centre Hospitalier Universitaire Amiens (H Dupont); Centre Hospitalier Universitaire de Bicêtre (J Duranteau); Centre Hospitalier Universitaire Reims (A Leon); CH Colmar (L Henry); CHG Armentieres (C Canevet); CHU Angers (L Dube); CHU Angers (H Julien); CHU Bicetre (A Nadia); CHU Brest (B Francois); CHU de Bordeaux (J Gérard); CHU Dijon Hopital Général (M Freysz); CHU Hôtel Dieu - APHP (G Remy); CHU Nantes (Y Blanloeil); Clinique Ambroise Paré (P Squara); General Hospital (J Korach); Grenoble University Hospital (M Durand); Groupe Hospitalier du Havre (C Gabriel); Hia Laveran (P Eric); Hopital Antoine Béclère APHP (F Jacobs); Hopital Bichat (R Bronchard); Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Lille (E Kipnis); Hopital Cochin Paris (M Moussa); Hôpital de Hautepierre (A Launoy); Hopital de la Croix Rousse (C Guérin); Hôpital Edouard Herriot (P Vanhems); Hôpital Maison Blanche (A Wynckel); Hôpital Raymond Poincaré (B Clair); Hôpital Saint-Louis (E Azoulay); Hôpital Tenon (J Fulgencio); Hôpitaux Civils de Colmar (Y Gottwalles); Hôpitaux Universitaires de Strasbourg (T Krummel); Hospices Civils de Lyon (A Lepape); La Rochelle Hospital (O Lesieur); Lariboisiere University Hospital (D Payen); Poissy Hospital (O Hérvé); Polyclinique Saint André (J Farkas); Rangueil Hospital (P Cougot); Réanimation Chirurgicale (Y Malledant); University Hospital of Bordeaux Haut-Lèvéque (O Joannes-Boyau); Germany: Academic Hospital Solingen (T Standl); Ameos Klinikum St.Salvator Halberstadt GMBH (U Sierig); Asklepios Fachkliniken München-Gauting (J Geiseler); Asklepios Klinik Langen (H Hopf); Behandlungszentrum Vogtareuth (M Burgau); Bergmannsheil Bochum (E Conrad-Opel); Bethanien-Krankenhaus (C Hermann); Bundeswehrkrankenhaus Ulm (M Ventzke); Charite/Campus Virchow-Klinikum (T Henneberg); Charite Berlin-Buch (H Loeser); Charité Campus, Mitte (C Spies); Charité Campus, Virchow Klinikum (C Spies); Charite Campus, Virchow (F Esposito); Charité Universitätsmedizin Berlin (H Zuckermann-becker); Clemenshospitl (R Scherer); Dominikus Krankenhaus (A Pauer); Drk-Kliniken Mark Brandenburg (S Kljucar); Drk-Krankenhaus Ratzeburg (K Delfs); Elisabeth-Krankenhaus Essen (E Blank); Ev. Kliniken Bonn Betriebsstätte Waldkrankenhaus (J Busch); Ev.-Freikirchliches Krankenhaus Rüdersdorf (K Wendt); Evang. Krankenhaus Mülheim (J Leßmann); Evangelische Kliniken Bonn Wadkrankenhaus (J Busch); Evangelisches Krankenhaus Bielefeld (F Bach); Friedrich Schiller University, Jena (Y Sakr); Gemeinschaftskrankenhaus Herdecke (T Berlet); Georg-August University of Göttingen (A Kernchen); Georg-August-University of Göttingen (M Quintel); Hanse-Klinikum Wismar (D Holst); Heart clinic of the University of Munich (E Kilger); Helfenstein Klinik (T Holubarsch); Helios Klinik Lengerich (C Raufhake); Helios-Klinikum Berlin-Buch (R, Kuhlen, C Stolt); Helios Klinikum Emil Von Behring (A Lubasch); Helios Klinikum Erfurt Gmbh (A Meier-Hellmann); Helios Klinikum Wuppertal Barmen (G Woebker); Henriettenstift (C Scharnofske); Herz-Jesu-Krankenhaus (M Breyer); Hochtaunus Kliniken Bad Homburg (T Risch); Hospital Links Der Weser (C Manhold); Icu In Drk Kliniken Mark Brandenburg (S Kljucar); J.W. Goethe - University Medical School Frankfurt Am Main (D Meininger); Johanniter Krankenhaus Bonn (C Greive); Johanniter Krankenhaus Stendal Ggmbh (J Rau); Jung-Stilling-Krankenhaus (A Seibel); Katharinenhospital (A Henn-beilharz); Katholisches Krankenhaus Hagen (R Wolbert); Krankenhaus Prignitz Gemmeinnützige GMBH (T Scherke); Klinik Am Eichert (J Martin); Klinik Für Herzchirurgie (M Rudolph); Klinik Füranästhesie, Operative Intensivmedizin U. Schmerztherapie (J Gleißner); Kliniken Ludwigsburg-Bietigheim GMBH (M Wolf); Kliniken Maria Hilf (F Schleibach); Klinikum Augsburg (U Jaschinski); Klinikum Bad Salzungen (A Lunkeit); Klinikum Darmstadt (M Welte); Klinikum Der J.W. Goethe-Universität (T Bingold); Klinikum Der Stadt Wolfsburg (K. Sydow); Klinikum Emden (K Kogelmann); Klinikum Forchheim (F Fischer); Klinikum Fuerth (B Fischer, M Schmid); Klinikum Grosshadern, Universität München (M Klein); Klinikum Harlaching Städtisches Klinikum Muenchen (A Bechtold); Klinikum Hildesheim (K Bodmann); Klinikum Kaufbeuren (J Klasen); Klinikum Landsberg (H Meyrl); Klinikum Lippe - Detmold (J Goetz); Klinikum Ludwigsburg (G Geldner); Klinikum Luedenscheid (T Helmes); Klinikum Meiningen GMBH (N Jensen); Klinikum Minden (H Eickmeyer, W Lengfelder); Klinikum Nürnberg (B Langenstein); Klinikum Rechts Der Isar (R Bogdanski); Klinikum Rechts Der Isar Der Technischen Universität München (S Jelen-Esselborn, A Umgelter); Klinikum Region Hannover (F Dörr); Klinikum Region Hannover Krankenhaus Großburgwedel (K Lüttje); Klinikum Region Hannover, Krankenhaus Oststadt-Heidehaus (D Heinemeyer); Klinikum Starnberg (M Uhl); Klinikum Stuttgart - Olgahospital (P Schirle); Klinikum Suedstadt (H Benad); Klinikum Traunstein (M Glaser); Klinikum Uelzen (W Panzer); Klinikum Worms (E Huettemann); Klinikverbund St. Ansgar, Krankenhaus Bassum (R Stierwaldt); Klinikverbund Süd-West (M Schappacher); Knappschaftskrankenhaus Bochum-Langendreer (E Müller); Krankenhaus Freyung (Rural Hospital) (W Stadlmeyer); Krankenhaus Lübbecke (M Fantini); Krankenhaus Mol GMBH Strausberg (B Dummer); Krankenhaus Nordwest (M Thörner); Krankenhaus Nordwest (V Jost); Krankenhaus Reinbek (T Loerbroks); Kreisklinik Trostberg (T Glück); Kreiskrankenhaus Bergstrasse (R Zimmermann); Kreiskrankenhaus Calw (R Clement); Kreiskrankenhaus Mechernich GMBH (R Hering); Kreiskrankenhaus Nagold (T Klinger); Kreiskrankenhaus Rottweil (J Mehl); Kreiskrankenhaus St. Marienberg Helmstedt (H Polozek); Leopoldina-Krankenhaus (A Rothhammer); Ludmillenstift (R Seidler); Lukas-Krankenhaus Bünde (P Lorenz); Lungenfachklinik Amsee Waren Mueritz (M Lutze); Marienhospital Bruehl (M Euler); Marienkrankenhaus Schwerte (M Heintz); Martin Luther Universität Halle (M Winkler); Medizinische Klinik (M Angstwurm); Mlu Halle-Wittenberg (K Krohe); Mueritz-Klinikum Waren (T Treu); Neurological Intensive Care Unit (T Steiner); Oberschwabenklinik Wangen (S Locher); Orthopädische Klinik Markgröningen (A Walz); Ostalb-Klinikum Aalen (P Zahn); Otto-Von-Guericke Universität Magdeburg (W Brandt); Scivias-Krankenhaus St. Josef (M Marks); Ska-Bileelfeld-Mitte (F Henning); St. Antonius Hospital (U Janssens); St. Hildegardis Krankenhaus Mainz (M Luethgens); St. Johannes Krankenhaus (W Theelen); St. Johannes-Hospital (M Sydow); St. Johannes-Hospital (M Weber); St. Josef-Hospital, Ruhr-Universität Bochum (A Meiser); St. Josefs-Hospital (C Deutschmann); St. Joseph Krankenhaus (C Buttner); St.-Marien Hospital Lünen (M Jokiel); St. Marienhospital Hamm (C Bozzetti); St. Vincentius Kliniken (B Jürgen); St.-Elisabeth Krankenhaus Köln-Hohenlind (F Fiedler); St.-Vincentius-Krankenhaus Speyer (K Wresch); Städtischen Kliniken Neuss - Lukaskrankenhaus (A Kremer); Städtisches Klinikum Karlsruhe (H Bleier); Städtisches Klinikum Wiesbaden, Dr.-Horst-Schmidt-Kliniken Hsk (M Rueckert); Staedtisches Klinikum Guetersloh (H Ditter); Staedtisches Klinikum Muenchen Gmbh - Klinikum Harlaching (C Peckelsen); Staedtisches Klinikum Muenchen Gmbh/Klinikum Bogenhausen (P Friederich); Staedtisches Klinikum München - Klinikum Neuperlach (K Weber); Tübingen University Hospital (W Krueger); Ubbo-Emmius-Klinik Aurich (R Lowack); Überlingen Hospital (A Michalsen); Uniklinikum Dresden (M Ragaller); Universitaetsklinikum des Saarlandes (A Groeschel); Universitaetsklinikum Mannheim (T Friedrich, U Hoffmann); Universität Rostock (M Hinz); Universitätsklinikum Der Martin-Luther-Universität Halle-Wittenberg (A Christel); Universitätsklinikum Dresden Carl Gustav Carus (M Ragaller); Universitätsklinikum Leipzig Aör (T Hartwig); Universitätsmedizin Berlin Charité Campus Benjamin Franklin (S Vögeler); University (M Weiss); University Childrens Hospital Hauner (K Reiter); University Hospital (T Schwab); University Hospital Cologne (U Trieschmann); University Hospital Dusseldorf (D Kindgen-milles); University Hospital Giessen and Marburg Gmbh - Giessen (J Engel); University Hospital Lübeck (B Sedemund-adib); University Hospital Mainz (M Lauterbach); University Hospital Marburg (M Max); University Hospital Muenster (T Volkert); University Hospital of Essen (C Waydhas); University Hospital of Mannheim (S Hien); University Hospital of Munich, LMU (J Briegel); University Hospital of Regensburg (V Guralnik); University Hospital Rwth Aachen (N Zoremba); University Hospital Tübingen (R Riessen); University Hospital Würzburg (W Müllges); University Medical Center Hamburg-Eppendorf (A Nierhaus); University of Erlangen (R Strauss); University of Freiburg (S Utzolino); University of Giessen (J Thul); University of Greifswald (P Abel, M Gründling, W Keßler); University of Heidelberg (K Scheuren); University of Leipzig (E Lothar, U Kaisers, D Schmitt, D Schneider); University of Rostock (D Vagts); University of Saarland (H Rensing); University Hospital Essen (B Schoch); Universty Hospital (K Kopp); Vivantes - Klinikum Neukoelln (H Gerlach); Vivantes Klinikum Prenzlauer Berg (M Corea); Vivantes-Klinikum Am Urban (A Uhrig); Westkuestenklinikum Heide (S Schroeder); Westküstenklinikum Heide (F Jordan); Westpfalz-Klinikum Kaiserslautern (T Huber); Zentralöklinikum Augsburg (M Bittinger) Greece: Ahepa University Hospital (E Sofianos); Athens University Medical School (A Armaganidis); Evangelismos Hospital (C Routsi); G.Papanikolaou (M Bitzani); General Hospital of Rethymno (A Chalkiadaki); Henry Dunant Hospital (A Michalopoulos); Hippokrateion Hospital Thessaloniki (E Mouloudi); Kat General Hospital (E Ioannidou); Kat Hospital (P Myrianthefs); Kat Hospital, Athens (D Koulenti); Konstantopoulio General Hospital (I Karampela); Lamia General Hospital (G Kyriazopoulos); Red Cross Hospital of Athens (K Mandragos); Thriassio Hospital of Eleusis (P Clouva-molyvdas); University Hospital of Ioannina (A Moraiti); University Hospital of Alexandroupolis (I Pneumatikos); University Hospital of Rion, Patras (K Filos); University Hospital of Thessaly (Larissa) (E Zakynthinos); University of Athens, Medical Shcool (A Kotanidou); Xanthi General Hospital (A Vakalos) Hong Kong: Northern District Hospital (A Cheng); Princess Margaret Hospital and Yan Chai Hospital (T Buckley); The Chinese University of Hong Kong (C Gomersall) Hungary: National Institute of Neurosurgery (K Kiss); Péterfy Hospital Budapest (P Tamási); Saint George Hospital Hungary (A Sarkany); Semmelweis University (A Csomos); University of Szeged (É Zöllei) India: Advanced Medicare Research Institute (S Todi); B.D.Petit Parsee General Hospital (F Udwadia); Bhailal Amin General Hospital (R Shah); Bombay Hospital (P Amin); Breach Candy Hospital Trust (F Udwadia); Care Hospitals (S Samavedam); Christian Medical College (A Mathai); Cumballa Hill Hospital & Heart Institute (M Patil); Deenanath Mangeshkar Hospital (S Jog); Dr. S. N. Medical College (M Gurjar); Escorts Heart Institute & Research Centre (M Vats); Fortis Healthcare (A Varma); Global Hospitals (P Gopal); Hinduja Hospital & Medical Research Center (F Kapadia); Indraprastha Apoolo Hospitals (R Chawla); Jehangir Hospital (S Iyer); Kalinga Hospital (S Sahu); Kasturba Hospital (C Bakshi); Lokmanya Care Hospital (D Ambike); Max Super Speciality Hospital (D Govil); Medical Trust Hospital, Cochin (V Karipparambath); Nh Hospital (J Chacko); Ruby Hall Clinic (P Sathe); Rungta Hospital (N Rungta); Saifee Hospital (C Jani); Seth Ramdas Shah Memorial Hospital & Research Centre (A Bhome); Shree Medical Foundation (S Prayag); Sir Ganga Ram Hospital (S Ray); Sundaram Medical Foundation (R Rajagopalan); Tata Memorial Hospital (J Divatia); Wockhardt Hospital (R Da costa); Wockhrdt Hospital (T Shyam Sunder) Indonesia: Bintaro International Hospital (P Wibowo); Hasan Sadikin Hospital (T Maskoen); Pantai Indah Kapuk Hospital (T Sugiman) Islamic Republic of Iran: Imamreza Hospital (S Nowruzinia); Laleh Hospital (A Lotfi); Tehran University of Medical Sciences (A Mahmoodpoor) Ireland: Amnch (M Donnelly); Cork University Hospital (D Breen); Mater Misercordiae University Hospital (S Ng); University Hospital Galway (J Bates) Israel: Hadassah Medical Center (C Sprung); Haemek Medical Center (A Lev); Kaplan Medical Center (E Kishinevsky); Rabin Medical Center (J Cohen); Soroka Medical Center (S Sofer) Italy: A.O Niguarda (S Vesconi); A.O. Ospedale Di Circolo Di Busto Arsizio (S Greco); A.O. Treviglio-Caravaggio (M Borelli); Anestesia E Rianimazione 2 Prof.De Gaudio (P Cecilia); Arnas Ospedale Civico (M Sapuppo); ASL 10 (A Lazzero); ASL 10 Florence Hospital San Giovanni Di Dio (V Mangani); Azienda Ospedaliera Desenzano (N Petrucci); Azienda Ospedaliera Di Melegnano (M Minerva); Azienda Ospedaliera G. Rummo (E De blasio); Azienda Ospedaliera Polo Universitario San Paolo (S Marzorati); Azienda Ospedaliera Santa Maria Alle Scotte (R Rosi); Azienda Ospedaliera Universitaria P.Giaccone Policlinico (A Giarratano); Azienda Ospedaliera-Universitaria Udine (O Margarit); Azienda Ospedaliero -Universitaria (A Guberti); Azienda Ospedaliero-Universitaria S.M.Misericordia (S Scolz); Clinica San Gaudenzio (E Stelian); Fondazione IRCCS Policlinico San Matteo (V Emmi); Fondazione Ospedale Maggiore Policlinico, Mangiagalli Regina Elena (M Caspani); Fondazione Poliambulanza (A Rosano); H San Gerardo (C Abbruzzese); Hospital Panico Tricase (S Colonna); Humanitas Gavazzeni (R Ceriani); II Faculty of Medicne I University of Rome- Osp. S.Andrea (R De Blasi); S. Salvatore Hospital (L Panella); IRCCS Casa Sollievo Della Sofferenza (F Borrelli); Istituto Nazionale Tumori Regina Elena (P Lorella); KH Brixen (H Ruatti); Osepdali Riuniti Di Ancona (C Munch); Ospedale "Ca Foncello" - Treviso (Italia) (C Sorbara); Ospedale "Santa Croce" - ASL 8 (G Fiore); Ospedale Bufalini-Cesena (A Chieregato); Ospedale Di Circolo E Fondazione Macchi (V Conti); Ospedale Di Massa (A Guadagnucci); Azienda USL Piacenza (M Pizzamiglio); Ospedale Ferrarotto (M Locicero); Ospedale Maggiore Ausl Bologna (I Marri); Ospedale Maggiore Policlinico Milano (A Sicignano); Ospedale Maggiore Policlinico, Mangiagalli E Regina Elena, IRCCS Milano (V Conte); Ospedale Mugello Azienda Sanitaria Firenze (R Oggioni); Ospedale Niguarda Ca Granda, Milano (A De Gasperi); IRCCS Centro di Riferimento Oncologico della Basilicata (P De Negri); Ospedale Provinciale Pistoia (G Santagostino); Ospedale S. 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Cuore (L Martinelli); University-Hospital Careggi, Florence, (L Gianesello); University Hospital Policlinico Di Catania (A Gullo); University of Rome "La Sapienza" (A Morelli); UTI Trapianti (G Biancofiore); University of Udine (G Della Rocca) Japan: Kyoto Prefectural University of Medicine (S Hashimoto); Nagoya University Hospital (M Onodera); Oosaka-Fu Saiseikai Suita Hospital (A Kobayashi); Sanai Hospital (T Shinozuka); Tokushima University School of Medicine (H Imanaka); Tokyo Medical University, Hachioji Medical Center (T Ikeda); Tokyo Women’s Medical University (A Yaguchi) Latvia: Hospital of Traumatology and Orthopedics (I Misane); 7th Hospital of Riga (A Piebalga) Lebanon: Lebanese Canadian Hospital (A Moughaghab) Lithuania: Medicine University of Kaunas (V Pilvinis); Vilnius University Emergency Hospital (S Vosylius); Vilnius University Hospital Santariskiu Clinics (M Balciunas, G Kekstas) Luxembourg: Centre Hospitalier de Luxembourg (H Margaret); Clinique Ste Thérèse (M Klop) Macedonia: Clinic For Infectious Diseases (K Grozdanovski); General Hospital Stip (B Eftimova) Malaysia: Faculty of Medicine, Universiti Kebangsaan Malaysia (S Wafa); Hospital Pulau Pinang (C Lim); Hospital Tengku Ampuan Afzan, Kuantan, Pahang (M Mat nor); Kuala Lumpur Hospital (L Tai); National Heart Institute (S Syed Mohd Tahir); Sarawak General Hospital (N Idris); Sultanah Aminah Hospital (C Tan) Malta: St Luke’s Hospital (M Borg); Mexico: Angeles Metropolitano Hospital (E Manzo); Centro Medico Lic.Adolfo Lopez Mateos (H Gutierrez Morales); Hgr 25 Imss Zaragoza (P Miguel); Hospital Angeles Clinica Londres (A Villagomez); Hospital Angeles del Carmen (A Bassols); Hospital Civil de Guadalajara "Fray Antonio Alcalde" (G Aguirre); Hospital Español de México (U Cerón); Hospital General Bernardo J. 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