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2. Voeding op de intensive care

Author

van der Hoven, Ben, Lakenman, Patty, Soeters, Maarten, editor, Wierdsma, Nicolette, editor, Kruizenga, Hinke, editor, and Bouma, Gerd, editor

Published
2023
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4. Association between fat-free mass and survival in critically ill patients with COVID-19:A prospective cohort study

Author

Lakenman, Patty L. M., van Marwijk, Iris, van der Hoven, Ben, van Bommel, Jasper, Joosten, Koen F. M., Olieman, Joanne F., Lakenman, Patty L. M., van Marwijk, Iris, van der Hoven, Ben, van Bommel, Jasper, Joosten, Koen F. M., and Olieman, Joanne F.

Abstract

Background: Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. Methods: This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30–90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. Results: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m 2, 54% had obesity (BMI > 30 kg/m 2). Median weight change during ICU stay was −3 kg: +3 kg FM and −6 kg FFM (−4 kg SMM). Body composition changed significantly (P < 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72–0.96; P = 0.015). Patients with optimal protein intake (>80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received <80%. Conclusion: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.

Published
2024

5. Association between fat‐free mass and survival in critically ill patients with COVID‐19: A prospective cohort study.

Author

Lakenman, Patty L. M., van Marwijk, Iris, van der Hoven, Ben, van Bommel, Jasper, Joosten, Koen F. M., and Olieman, Joanne F.

Subjects
COVID-19, CRITICALLY ill, BODY composition, WEIGHT loss, MUSCLE mass, COHORT analysis
Abstract

Background: Most critically ill patients with COVID‐19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. Methods: This prospective cohort study included adult critically ill patients with COVID‐19. Body composition (fat‐free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30–90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. Results: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m2, 54% had obesity (BMI > 30 kg/m2). Median weight change during ICU stay was −3 kg: +3 kg FM and −6 kg FFM (−4 kg SMM). Body composition changed significantly (P < 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72–0.96; P = 0.015). Patients with optimal protein intake (>80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received <80%. Conclusion: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Nutritional intake and gastro-intestinal symptoms in critically ill COVID-19 patients

Author

Lakenman, P.L.M., van Schie, J.C., van der Hoven, Ben, Baart, Sara, Eveleens, Renate, van Bommel, Jasper, Olieman, Joanne, Joosten, Koen, Lakenman, P.L.M., van Schie, J.C., van der Hoven, Ben, Baart, Sara, Eveleens, Renate, van Bommel, Jasper, Olieman, Joanne, and Joosten, Koen

Abstract

Background & aims: Critically ill COVID-19 patients seem hypermetabolic and difficult to feed enterally, due to gastro-intestinal (GI) symptoms such as high gastric residual volumes (GRV) and diarrhea. Our aim was to describe the association of nutritional intake and GI symptoms during first 14 days of ICU admission. Methods: Observational study including critically ill adult COVID-19 patients. Data on nutritional intake [enteral nutrition (EN) or parenteral nutrition] and GI symptoms were collected during 14 days after ICU admission. Target energy and protein feeding goals were calculated conform ESPEN guidelines. GI symptoms included GRV (ml/d), vomiting, abdominal distension, and faeces (ml/d). High GRV's were classified as ≥2 times ≥150 ml/d and diarrhea as Bristol stool chart ≥6. GI symptoms were defined as mild if at least one symptom occurred and as moderate when ≥2 symptoms occurred. Acute gastrointestinal injury (AGI) grades of III were classified as GI dysfunction and grades of IV were considered as GI failure with severe impact on distant organs. Linear mixed model analysis was performed to explore the development of nutritional intake and GI symptoms over time at day (D) 0, 4, 10, and 14. Results: One hundred and fifty patients were included [75% male; median age 64 years (IQR 54–70)]. BMI upon admission was 28 kg/m2 (IQR 25–33), of which 43% obese (BMI > 30 kg/m2). Most patients received EN during admission (98% D4; 96% D10-14). Mean energy goals increased from 87% at D4 to 93% D10-14 and protein goals (g/kg) were increasingly achieved during admission (84% D4; 93% D10-14). Presence of moderate GI symptoms decreased (10% D0; 6% D4-10; 5% D14), reversely mild GI symptoms increased. Occurrence of GI dysfunction fluctuated (1% D0; 18% D4; 12% D10; 8% D14) and none of patients developed grade IV GI failure. Development of high GRV fluctuated (5% D0; 23% D4; 14% D10; 8% D14) and occurrence of diarrhea slightly increased during

Published
2022

10. Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19

Author

Solanich, Xavier, primary, Vargas-Parra, Gardenia, additional, van der Made, Caspar I., additional, Simons, Annet, additional, Schuurs-Hoeijmakers, Janneke, additional, Antolí, Arnau, additional, del Valle, Jesús, additional, Rocamora-Blanch, Gemma, additional, Setién, Fernando, additional, Esteller, Manel, additional, van Reijmersdal, Simon V., additional, Riera-Mestre, Antoni, additional, Sabater-Riera, Joan, additional, Capellá, Gabriel, additional, van de Veerdonk, Frank L., additional, van der Hoven, Ben, additional, Corbella, Xavier, additional, Hoischen, Alexander, additional, and Lázaro, Conxi, additional

Published
2021
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11. Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19

Author

Solanich, Xavier, Vargas-Parra, Gardenia, van der Made, Caspar I., Simons, Annet, Schuurs-Hoeijmakers, Janneke, Antolí, Arnau, del Valle, Jesús, Rocamora-Blanch, Gemma, Setién, Fernando, Esteller, Manel, van Reijmersdal, Simon V., Riera-Mestre, Antoni, Sabater-Riera, Joan, Capellá, Gabriel, van de Veerdonk, Frank L., van der Hoven, Ben, Corbella, Xavier, Hoischen, Alexander, Lázaro, Conxi, Solanich, Xavier, Vargas-Parra, Gardenia, van der Made, Caspar I., Simons, Annet, Schuurs-Hoeijmakers, Janneke, Antolí, Arnau, del Valle, Jesús, Rocamora-Blanch, Gemma, Setién, Fernando, Esteller, Manel, van Reijmersdal, Simon V., Riera-Mestre, Antoni, Sabater-Riera, Joan, Capellá, Gabriel, van de Veerdonk, Frank L., van der Hoven, Ben, Corbella, Xavier, Hoischen, Alexander, and Lázaro, Conxi

Abstract

Introduction: Loss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19. Methods: We prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants. Results: TLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect. Conclusions: This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

Published
2021

13. Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model

Author

van der Hoven, Ben, van Pelt, Hans, Swart, Eleonore L., Bonthuis, Fred, Tilanus, Huug W., Bakker, Jan, and Gommers, Diederik

Subjects
Blood flow -- Measurement, Blood flow -- Physiological aspects, Blood flow -- Research, Liver -- Physiological aspects, Liver -- Research, Sepsis -- Complications and side effects, Sepsis -- Research, Sorbitol -- Physiological aspects, Sorbitol -- Research, Biological sciences
Abstract

van der Hoven B, van Pelt H, Swart EL, Bonthuis F, Tilanus HW, Bakker J, Gommers D. Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model. Am J Physiol Gastrointest Liver Physiol 298: G177-G181, 2010. First published November 25, 2009; doi: 10.1152/ajpgi.90688.2008.--Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 [+ or -] 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously (Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 rag/100 g body wt per rain) or a bolus (3 rag/100 g body wt) of a 5% D-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between ([T.sub.1/2,sorbitol] = 9 min), a crossover was done. The hepatic clearance of D-sorbitol in the control group showed a good correlation between bolus and SS (Spearman's r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) (r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance (r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF (r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis. microcirculation; rats; sepsis doi: 10.1152/ajpgi.90688.2008.

Published
2010

14. Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19: a case series

Author

Solanich, Xavier, primary, Vargas-Parra, Gardenia, additional, van der Made, Caspar I., additional, Simons, Annet, additional, Schuurs-Hoeijmakers, Janneke, additional, Antolí, Arnau, additional, del Valle, Jesús, additional, Rocamora-Blanch, Gemma, additional, Setién, Fernando, additional, Esteller, Manel, additional, Riera-Mestre, Antoni, additional, Sabater-Riera, Joan, additional, Capellá, Gabriel, additional, van de Veerdonk, Frank L., additional, van der Hoven, Ben, additional, Corbella, Xavier, additional, Hoischen, Alexander, additional, and Lázaro, Conxi, additional

Published
2021
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16. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

Author

Pachl, Jan, Svoboda, Petr, Jacobs, Frederique, Vandewoude, Koenraad, van der Hoven, Ben, Spronk, Peter, Masterson, Gary, Malbrain, Manu, Aoun, Mickael, Garbino, Jorge, Takala, Jukka, Drgona, Lubos, Burnie, James, and Matthews, Ruth

Subjects
Amphotericin B -- Analysis, Heat shock proteins -- Analysis, Candidiasis -- Research, Candidiasis -- Physiological aspects, Candidiasis -- Care and treatment, Health, Health care industry
Published
2006

18. Routine Use of the Confusion Assessment Method for the Intensive Care Unit: A Multicenter Study

Author

van Eijk, Maarten M., van den Boogaard, Mark, van Marum, Rob J., Benner, Paul, Eikelenboom, Piet, Honing, Marina L., van der Hoven, Ben, Horn, Janneke, Izaks, Gerbrand J., Kalf, Annette, Karakus, Attila, Klijn, Ine A., Kuiper, Michael A., de Leeuw, Frank-Erik, de Man, Tjarda, van der Mast, Roos C., Osse, Robert-Jan, de Rooij, Sophia E., Spronk, Peter E., van der Voort, Peter H., van Gool, Willem A., and Slooter, Arjen J.

Published
2011
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23. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial.

Author

Vanderbeke, Lore, Janssen, Nico A. F., Bergmans, Dennis C. J. J., Bourgeois, Marc, Buil, Jochem B., Debaveye, Yves, Depuydt, Pieter, Feys, Simon, Hermans, Greet, Hoiting, Oscar, van der Hoven, Ben, Jacobs, Cato, Lagrou, Katrien, Lemiale, Virginie, Lormans, Piet, Maertens, Johan, Meersseman, Philippe, Mégarbane, Bruno, Nseir, Saad, and van Oers, Jos A. H.

Subjects
INFLUENZA, PULMONARY aspergillosis, CRITICALLY ill, INTENSIVE care patients, RESPIRATORY insufficiency, INFLUENZA complications, INFLUENZA prevention, INTENSIVE care units, RESEARCH, HETEROCYCLIC compounds, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, CATASTROPHIC illness, COMPARATIVE studies
Abstract

Purpose: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA.Methods: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population).Results: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment.Conclusion: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study

Author

Lestrade, Pieter P, primary, Bentvelsen, Robbert G, additional, Schauwvlieghe, Alexander F A D, additional, Schalekamp, Steven, additional, van der Velden, Walter J F M, additional, Kuiper, Ed J, additional, van Paassen, Judith, additional, van der Hoven, Ben, additional, van der Lee, Henrich A, additional, Melchers, Willem J G, additional, de Haan, Anton F, additional, van der Hoeven, Hans L, additional, Rijnders, Bart J A, additional, van der Beek, Martha T, additional, and Verweij, Paul E, additional

Published
2018
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28. A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Author

Pachl, Jan, Svoboda, Petr, Jacobs, Frédérique, Vandewoude, Koenraad, van der Hoven, Ben, Spronk, Peter, Masterson, Gary, Malbrain, Manu, Aoun, Mickael, Garbino, Jorge, Takala, Jukka, Drgona, Lubos, Burnie, James, Matthews, Ruth, Pachl, Jan, Svoboda, Petr, Jacobs, Frédérique, Vandewoude, Koenraad, van der Hoven, Ben, Spronk, Peter, Masterson, Gary, Malbrain, Manu, Aoun, Mickael, Garbino, Jorge, Takala, Jukka, Drgona, Lubos, Burnie, James, and Matthews, Ruth

Abstract

Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species. Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P < .001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P < .001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P < .001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated. Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis

Published
2017

30. Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study.

Author

Lestrade, Pieter P, Bentvelsen, Robbert G, Schauwvlieghe, Alexander F A D, Schalekamp, Steven, Velden, Walter J F M van der, Kuiper, Ed J, Paassen, Judith van, van der Hoven, Ben, Lee, Henrich A van der, Melchers, Willem J G, Haan, Anton F de, Hoeven, Hans L van der, Rijnders, Bart J A, Beek, Martha T van der, and Verweij, Paul E

Subjects
ANTIFUNGAL agents, COMPARATIVE studies, DRUG resistance in microorganisms, LONGITUDINAL method, RESEARCH methodology, PULMONARY aspergillosis, SURVIVAL analysis (Biometry), RETROSPECTIVE studies, DESCRIPTIVE statistics, VORICONAZOLE, PHARMACODYNAMICS
Abstract

Background Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%–100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. Methods A 5-year retrospective cohort study (2011–2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. Results Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P =.017) and 25% on day 90 (62% vs 37%; P =.0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P =.045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P =.016), despite switching to appropriate antifungal therapy after a median of 10 days. Conclusions Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Intestinal fatty acid binding protein as a marker for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; study protocol for a prospective cohort study (I-Fabulous study)

Author

Strang, Steven, van Waes, O.J.F., van der Hoven, Ben, Ali, Samir, Verhofstad, Michiel, Pickkers, P, Van Lieshout, Esther M.M., Strang, Steven, van Waes, O.J.F., van der Hoven, Ben, Ali, Samir, Verhofstad, Michiel, Pickkers, P, and Van Lieshout, Esther M.M.

Abstract

Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have detrimental effects on all organ systems and are associated with increased morbidity and mortality in critically ill patients admitted to an intensive care unit. Intra-bladder measurement of the intra-abdominal pressure (IAP) is currently the gold standard. However, IAH is not always indicative of intestinal ischemia, which is an early and rapidly developing complication. Sensitive biomarkers for intestinal ischemia are needed to be able to intervene before damage becomes irreversible. Gut wall integrity loss, including epithelial cell disruption and tight junctions breakdown, is an early event in intestinal damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and blood specifically from damaged intestinal epithelial cells. Claudin-3 is a specific protein which is excreted in urine following disruption of intercellular tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be used as a diagnostic tool for identifying patients at risk for IAP-related complications. Methods/Design: In a multicenter, prospective cohort study 200 adult patients admitted to the intensive care unit with at least two risk factors for IAH as defined by the World Society of the Abdominal Compartment Syndrome (WSACS) will be included. Patients in whom an intra-bladder IAP measurement is contra-indicated or impossible and patients with inflammatory bowel diseases that may affect I-FABP levels will be excluded. The IAP will be measured using an intra-bladder technique. During the subsequent 72 hours, the IAP measurement will be repeated every six hours. At these time points, a urine and serum sample will be collected for measurement of I-FABP and Claudin-3 levels. Clinical outcome of patients during their stay at the intensive care unit will be monitored using the Sequential Organ Failure Assessment (SOFA) score. Discussion: Successful completion of this trial

Published
2015

39. Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life

Author

Kompanje, Erwin, van der Hoven, Ben, Bakker, Jan, Kompanje, Erwin, van der Hoven, Ben, and Bakker, Jan

Abstract

Background: A considerable number of patients admitted to the intensive care unit (ICU) die following withdrawal of mechanical ventilation. After discontinuation of ventilation without proper preparation, excessive respiratory secretion is common, resulting in a 'death rattle'. Post-extubation stridor can give rise to the relatives' perception that the patient is choking and suffering. Existing protocols lack adequate anticipatory preparation to respond to all distressing symptoms. Methods: We analyzed existing treatment strategies in distressing symptoms after discontinuation of mechanical ventilation. Conclusion: The actual period of discontinuation of mechanical ventilation can be very short, but thoughtful anticipation of distressing symptoms takes time. There is an ethical responsibility to anticipate and treat (iatrogenic) symptoms such as pain, dyspnea-associated respiratory distress, anxiety, delirium, post-extubation stridor, and excessive broncho-pulmonary secretions. This makes withdrawal of mechanical ventilation in ICU patients a thoughtful process, taking palliative actions instead of fast terminal actions. We developed a flowchart covering all possible distressing symptoms that can occur after withdrawal of mechanical ventilation and extubation. We recommend a two-phase process. Six hours before extubation, enteral feeding should be stopped and parenteral fluids reduced, overhydrated patients should be dehydrated with furosemide, administration of sedatives (for distress) and opioids (for pain and/or dyspnea) should be continued or started and methylprednisolone should be given in anticipation of stridor after extubation. Thirty minutes before extubation, Butylscopolamine should be given and methylprednisolone repeated. After this the patient should be extubated to secure a dying process as natural as possible with the lowest burden due to distress.

Published
2008

47. GUT LUMINAL ENDOTOXIN REDUCES ISCHEMIAREPERFUSION INJURY OF THE SMALL GUT IN GERMFREE PIGS

Author

van der Hoven, Ben, Nabuurs, Marius, Leengoed, Leo A. M. G. van, Groeneveld, Johan A. B., and Thijs, Lambertus G.

Abstract

Translocation of luminal bacteria and their products through the intestinal mucosa during ischemiareperfusion IR may modify IR injury. To test this hypothesis, 16 germfree pigs were studied prior to and after clamping the superior mesenteric artery SMA and 12 pigs served as controls. Nine pigs in the IR and 5 in the control group received endotoxin intragastrically, 60 min before baseline. Gut absorption of an inert indicator polyethyleneglycol PEG 3350, gut intraluminal PCO2tonometry, and systemic and regional hemodynamic variables were measured up to 4 h after baseline. Gut blood flow was stopped during clamping, some reactive hyperemia occurred up to 30 min after declamping in the IR groups, independently of prior endotoxin administration. Gut intraluminalarterial PCO2gradients were elevated in IR versus control groups during I and for some time during R, prior endotoxin had no effect. However, in controls without and with luminal endotoxin, PEG urinary excretion, as percentage of the dose administered, was 0.12 ± 0.12 and 0.17 ± 0.07, respectively, while it measured 1.82 ± 0.70 in the IR group and 0.55 ± 0.37 in the IR and endotoxin groups, respectively P< 0.001. The data suggest that gut luminal endotoxin ameliorates IR injury of the gut wall in germfree pigs, without altering changes in gut perfusion adequacy and systemic hemodynamics.

Published
2001

48. A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Author

Pachl, Jan, Svoboda, Petr, Jacobs, Frédérique, Vandewoude, Koenraad, van der Hoven, Ben, Spronk, Peter, Masterson, Gary, Malbrain, Manu, Aoun, Mickael, Garbino, Jorge, Takala, Jukka, Drgona, Lubos, Burnie, James, Matthews, Ruth, Pachl, Jan, Svoboda, Petr, Jacobs, Frédérique, Vandewoude, Koenraad, van der Hoven, Ben, Spronk, Peter, Masterson, Gary, Malbrain, Manu, Aoun, Mickael, Garbino, Jorge, Takala, Jukka, Drgona, Lubos, Burnie, James, and Matthews, Ruth

Abstract

Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species. Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P < .001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P < .001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P < .001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated. Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis

49. Mortality after surgery in Europe: a 7 day cohort study

Author

Pearse, R, Moreno, R, Bauer, P, Pelosi, P, Metnitz, P, Spies, C, Vallet, B, Vincent, J, Hoeft, A, Rhodes, A, Fagnoul, D, van Obbergh, L, Al Subaie, N, Arif, F, Cashman, J, Cecconi, M, Edsell, M, Fossati, N, Hammond, S, Hamilton, M, Lonsdale, D, Moran, C, Siegmueller, C, Velzeboer, F, Wong, P, Awlakpui, E, Scheidemann, M, Wittmann, M, Damster, S, Golder, K, Hewson, R, Januszewska, M, Leva, B, Ramos, V, Hoste, E, Huyghens, L, Jacobs, R, Van Mossevelde, V, Opdenacker, G, Poelaert, J, Spapen, H, Leleu, K, Rijckaert, D, De Decker, K, Foubert, L, De Neve, N, Biston, P, Piagnerelli, M, Collin, V, den Blauwen, N, Clauwaert, C, De Crop, L, Verbeke, A, Derumeaux, P, Gardin, C, Kindt, S, Louage, S, Verhamme, B, Druwé, P, Lahaye, I, Rosseel, F, Rutsaert, R, Vanlinthout, L, De Kock, M, Forget, P, Georges, P, Grosu, I, Kahn, D, Lois, F, Momeni, M, Pospiech, A, Yemnga, B, Jadoul, J, Malbrain, M, Bosinceanu, D, Collard, E, Jorens, P, Reyntiens, D, Smitz, C, Vercauteren, M, Goranović, T, Mazul Sunko, B, Toplice, K, Oremuš, K, Bešlić, G, Duzel, V, Hauptman, A, Peremin, S, Šribar, A, Župčić, M, Brod, S, Mirković, I, Šarić Bauer, Z, Belavić, M, Blažanin, B, Katušin, M, Brozović Krijan, A, Mišković, P, Šimić Korać, N, Topić, J, Žilić, A, Žuni, J, Acan, I, Adanić, M, Ivanov, N, Pavičić Šarić, J, Tomulić, K, Visković, N, Bošnjak, S, Haršanji Drenjančevic, I, Kristek, G, Kvolik, S, Markić, S, Stojanovic Rakipovic, A, Katarina Tot, O, Venzera Azenic, D, Kalagac Fabris, L, Bačak Kocman, I, Balenović, I, Bandić, D, Judith Deutsch, P, Divjak, L, Filipović, I, Gužvinec, Z, Krznarić, Z, Lončarić, Y, Magaš, J, Mitrović, M, Okić, M, Pavlek, M, Ramov, E, Rezek, K, Sekulić, A, Tomasevic, B, Mirić, M, Tomašević, A, Tomić Mahečić, T, Vrbanović, V, Bobinac, M, Božić, A, Debelic, D, Frkovic, V, Batinica, I, Baranović, S, Gavranović, Ž, Kikec, M, Maldini, B, Marić, S, Agnić, I, Delić, N, Dropulić, N, Kljaković Gašpić, T, Ilić, D, Ivančev, B, Karanović, N, Kuščević, D, Marović, Z, Milić, M, Nevešćanin, A, Petković, T, Smoje, M, Brozović, G, Jelisavac, M, Matolić, M, Oberhofer, D, Marija Pavičić, A, Šakić, K, Delija Bozovic, M, Kotorac Krecek, Z, Krobot, R, Andabaka, T, Bratanić, M, Dzepina, O, Kraljev, M, Šeric, J, Šimurina, T, Grujić, R, Nacevski Bulaja, B, Barižon, M, Danira, V, Dražen, B, Dušanka, K, Bašić Halužan, M, Joško, Ž, Katica, R, Labor, M, Grgurević Marinković, T, Mihovilčević, D, Marija, B, Srečko, M, Vranković, S, Kyprianou, T, Neophytou, K, Cerny, V, Cvachovec, K, Belikova, B, Drab, M, Hudacek, K, Krikava, I, Stourac, P, Zadrazilova, K, Bicek, V, Brabcová, M, Klozová, R, Vajter, J, Vymazal, T, Toft, P, Blichfeldt, L, Dilling Hansen, B, Moller, K, Sylvest Nielsen, J, Frederiksen, J, Dohn Andersen, J, Peter Kühne, J, Leivdal, S, Stendell, L, Simonsen, M, Konrad Zoltowski, M, Salman Ali, Z, Freundlich, M, Pilypaite, J, Groes Clausen, N, Thorup, L, Hansen, F, Bestle, M, Steen Hansen, C, Afshari, A, Bastholm Bille, A, Lefort, M, Secher, E, Liboriussen, L, Herodes, V, Härma, 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Crooks, N, Gao Smith, F, Melody, T, Snaith, C, Patel, J, Parekh, D, Yeung, J, Loughnan, B, Moosajee, V, Rope, T, Edger, L, Dawson, J, Hadfield, D, Hopkins, P, Mcdonald, L, Willars, C, Campbell, G, Craig, J, Ladipo, K, Lockwood, G, Moreno, J, Ballington, R, Hamandishe, S, Rogerson, D, Cowman, S, Hayden, P, Pinto, N, Sandhar, T, Arawwawala, D, Brotherston, L, Mitchell Inwang, C, Walsh, H, Alagarsamy, F, Goon, S, Karcheva, S, Krepska, A, Mckinney, B, Patil, V, Batchelor, N, Day, C, Finch, L, Gibson, C, Grayling, M, Hubble, S, Key, W, Knight, T, Loosley, A, Margetts, P, Stewart, H, Bewley, J, Hurley, K, Murphy, R, Philpott, C, Pollock, K, Sweet, K, Thomas, M, Tucker, K, Windsor, D, Conway, D, Gold, S, Quraishi, T, Cupitt, J, Baddeley, S, Brown, J, Foo, I, Mantle, D, Carvalho, P, Huddart, S, Kirk Bayley, J, Smith, R, Milligan, L, Poulose, S, Sarkar, S, Nolan, J, Pedley, E, Padkin, A, Pesian, S, Rajamanickam, S, Ramkumar, K, Crayford, A, Turner, A, Bottrill, F, Webb, S, Jhanji, S, Maccallum, N, Wessels, K, Wigmore, T, Meikle, A, Wilson, S, White, S, Bonnett, A, Rushton, A, Williams, C, Zuzan, O, Hall, A, Montgomery, J, Piggot, A, Read, R, Stocker, M, Tamm, T, Agarwal, B, Ward, S, Brown, L, Joy, M, Venkatesh, S, Hughes, T, Zsisku, L, Roy, A, Hooper, V, Mouland, J, Nightingale, J, Rose, S, Chiam, P, Chohan, H, Dickson, C, Gibb, S, Higham, C, Harvey, C, Janarthanan, C, Jones, L, Kapoor, A, Moll, M, Roberts, L, Saunders, D, Arnold, G, Gibbs, C, Jhurgursing, M, Pierro, D, Pritchard, F, Doyle, P, Templeton, M, Wilson, R, Zantua, K, Collyer, T, Featherstone, J, Worton, R, Bruce, J, Mcguigan, K, Price, G, Moreton, S, Pulletz, M, Anderson, H, Baxter, I, Beckingsale, A, Callaghan, M, Datta, A, Gollogly, J, Izod, C, Lobaz, S, Macfie, C, Patel, M, Payne, H, Singh, R, Timms, G, Mcleod, S, O'Brian, P, Horner, E, Joshi, V, Stuart Smith, K, Seale, T, Bolger, C, Collins, H, Ekins, E, Hawkins, L, Jonas, M, Linford, K, Wadams, B, Beach, M, Vizcaychipi, M, Jewsbury, W, Davies, S, Balaji, P, Kangaraj, M, Pissay, N, Smith, N, Gopalakrishnan, S, Mackinnon, J, Strandvik, G, Francis, R, Jennings, A, Keating, M, Kumar, S, Leese, S, Magee, C, Pilsbury, J, Ralph, J, Riddington, D, Sachdeva, R, Snelson, C, Vasanth, S, Wilde, J, Lavender, B, Lyons, R, Watters, M, Adams, T, Dyer, S, Tindall, L, Claxton, A, Netke, M, Akouds, E, Bates, D, Gallagher, H, Hatton, J, Holroyd, W, Mitra, A, Nurse, T, Reed, D, Desikan, S, Barber, R, Childs, S, O'Carroll Kuehn, B, Wyldbore, M, Al Abdaly, A, Amatya, S, Bhaskaran, S, Chandan, G, Chaudhry, S, Chikungwa, M, Earnshaw, G, Grewal, M, Haque, S, Hawkins, J, Javaid, A, Jackson, C, Kamel, M, Marla, R, Mculloch, D, Parker, T, Salib, Y, Saravanmuthu, R, Secker, C, Sockalingam, S, Taylor, A, Austine, P, Kanade, V, Paal, D, Sam Mok, M, Burtenshaw, A, Davis, L, Ellahee, P, Freeman, D, Pierson, R, Wollaston, J, Karmarkar, A, Ball, C, Calton, E, Maxwell, L, Walker, R, Bland, M, Bullock, L, Harrison Briggs, D, Hodge, P, Krige, A, Dempsey, G, Hammell, C, Loveridge, R, Parker, R, Snell, J, Wright, C, Baker, A, Barr, K, Belcher, A, Bonnington, S, Bougeard, A, Fitzgerald, E, Ford, R, Gillard, C, Griffiths, L, Greenberg, L, Huber, J, Mathieu, S, Richardson, N, Tompsett, L, White, N, Patel, S, Corner, V, Thomas, R, Trodd, D, Wilson, J, Copley, E, Flutter, L, Hulme, J, Susarla, J, Thwaites, A, Jayasundera, S, Mcafee, S, Chantler, J, Mckechnie, S, Neely, J, Mouton, R, Scarth, E, Soar, J, Buss, J, Currie, V, Sange, M, Kuttler, A, Power, F, Alexander, D, Dunne, K, Shinner, G, Black, E, Haldane, G, Kerr, J, Saran, T, Ward, G, Jefferies, F, Alexander, P, Royle, A, Nahla, F, Bowles, T, Gregory, M, Ahern, R, Cartlidge, D, Craker, L, Thompson, C, Bidd, H, Giles, J, Manser, A, Parry, G, Chan, P, Das, D, Fahmy, N, Higgins, D, Khader, A, Stone, A, Leonardi, S, Rose, O, Bright, E, Ercole, A, Amir Rafi, M, Ramasamy, R, Sheshgiri, B, Merrill, C, Page, V, Walker, E, Harris, S, Hughes, S, Morrison, A, Razouk, K, Ayman, M, Jakeman, A, Mowatt, C, Paananen, S, Translational Physiology, Other departments, ACS - Amsterdam Cardiovascular Sciences, AII - Amsterdam institute for Infection and Immunity, Anesthesiology, APH - Amsterdam Public Health, Pearse Rupert, Moreno Rui P., Bauer Peter, Pelosi Paolo, Metnitz Philipp, Spies Claudia, Vallet Benoit, Vincent Jean-Loui, Hoeft Andrea, Rhodes Andrew, Fagnoul David, van Obbergh Luc, Al-Subaie Nawaf, Arif Fuhazia, Cashman Jeremy, Cecconi Maurizio, Edsell Mark, Fossati Nicoletta, Hammond Sarah Jane, Hamilton Mark, Lonsdale Dagan, Moran Carl, Siegmueller Claa, Velzeboer Freya, Wong Patrick, Awlakpui Eli, Scheidemann Mona, Wittmann Maria, Damster Sandrine, Golder Kim, Hewson Russell, Januszewska Marta, Leva Brigitte, Ramos Vasco, Hoste Eric, Huyghens Luc, Jacobs Rita, Van Mossevelde Veerle, Opdenacker Godelieve, Poelaert Jan, Spapen Herbert, Leleu Kri, Rijckaert Dirk, De Decker Koen, Foubert Luc, De Neve Nikolaa, Biston Patrick, Piagnerelli Michael, Collin Vincent, den Blauwen Nadia, Clauwaert Charlotte, De Crop Luc, Verbeke An, Derumeaux Pieter, Gardin Christophe, Kindt Sebastiaan, Louage Sofie, Verhamme Bruno, Druwé Patrick, Lahaye Ingrid, Rosseel Franci, Rutsaert Robert, Vanlinthout Luc, De Kock Marc, Forget Patrice, Georges Pascal, Grosu Irina, Kahn David, Lois Fernande, Momeni Mona, Pospiech Audrey, Yemnga Bernadette, Jadoul Jean-Luc, Malbrain Manu, Bosinceanu Dana, Collard Edith, Jorens Philippe, Reyntiens Dirk, Smitz Carine, Vercauteren Marcel, Goranović Tatjana, Mazul-Sunko Branka, Toplice Krapinske, Oremuš Krešimir, Bešlić Gabrijela, Duzel Viktor, Hauptman Ada, Peremin Sanja, Šribar Andrej, Župčić Miroslav, Brod Slavonski, Mirković Ivan, Šarić Bauer Zlata, Belavić Matija, Blažanin Božidar, Katušin Mirjana Lončarić, Brozović Krijan Antonija, Mišković Petar, Šimić-Korać Nataša, Topić Jasna, Žilić Antonio, Žuni Josip, Acan Ivana, Adanić Mirta, Ivanov Nikola, Pavičić Šarić Jadranka, Tomulić Katarina, Visković Nataša, Bošnjak Silvana, Haršanji Drenjančevic Ivana, Kristek Gordana, Kvolik Slavica, Markić Stela, Stojanovic Rakipovic Andreja, Katarina Tot Ozana, Venzera-Azenic Darija, Kalagac Fabris Lada, Bačak-Kocman Iva, Balenović Igor, Bandić Daniela, Judith Deutsch Patricia Adrianne, Divjak Loredana, Filipović Ina Grčić, Gužvinec Zvonka, Krznarić Zrinka, Lončarić Yvonne, Magaš Jelena Vadlja, Mitrović Marek, Okić Marija, Pavlek Mario, Ramov Elza, Rezek Karolina, Sekulić Ante, Tomasevic Bori, Mirić Mirjana, Tomašević Anita, Tomić Mahečić Tina, Vrbanović Vilena, Bobinac Mirna, Božić Alfred, Debelic Danijela, Frkovic Vedran, Batinica Inga Mladić, Baranović Senka, Gavranović Željka, Kikec Mirna, Maldini Branka, Marić Stela, Agnić Ivan, Delić Nikola, Dropulić Nataša, Kljaković Gašpić Toni, Ilić Darko, Ivančev Božena, Karanović Nenad, Kuščević Dorjan, Marović Zlatko, Milić Matija, Nevešćanin Ana, Petković Tatjana, Smoje Mario, Brozović Gordana, Jelisavac Milana, Matolić Martina, Oberhofer Dagmar, Marija Pavičić Ana, Šakić Kata, Delija Bozovic Margarita, Kotorac Krecek Zvjezdana, Krobot Renata, Andabaka Tatjana, Bratanić Mislav, Dzepina Orjana, Kraljev Martina, Šeric Julija, Šimurina Tatjana, Grujić Rosa, Nacevski-Bulaja Biljana, Barižon Mirna, Danira Vrančić, Dražen Bulaja, Dušanka Kimer, Bašić Halužan Marijana, Joško Žaja, Katica Roca, Labor Magda, Grgurević Marinković Tea, Mihovilčević Danči, Marija Bego, Srečko Marinković, Vranković Srdan, Kyprianou Theodoro, Neophytou Kyriako, Cerny Vladimir, Cvachovec Karel, Belikova Barbora, Drab Michal, Hudacek Kamil, Krikava Ivo, Stourac Petr, Zadrazilova Katarina, Bicek Vladimír, Brabcová Milena, Klozová Radka, Vajter Jaromír, Vymazal Tomáš, Toft Palle, Blichfeldt Louise, Dilling Hansen Bo, Moller Kirsten, Sylvest Nielsen Jeppe, Frederiksen Joachim, Dohn Andersen Johnny, Peter Kühne Jan, Leivdal Siv, Stendell Line, Simonsen Martin, Konrad Zoltowski Marcin, Salman Ali Zahida, Freundlich Morten, Pilypaite Jurgita, Groes Clausen Nicola, Thorup Line, Hansen Frank, Bestle Morten, Steen Hansen Christian, Afshari Arash, Bastholm Bille Ander, Lefort Michele, Secher Erik L., Liboriussen Lisbeth, Herodes Veiko, Härma Eve, Marvet Kadri, Pool Kristiina, Kallas Pille, Mägi Triinu-Kreete, Sütt Jaan, Vijar Kerli, Visk Evelin, Vinnal Mare, Ellermaa Jaanu, Liibusk Liia, Tikkerberi Artur, Falk Ilme, Mällo Esta, Talving Jaak, Pettilä Ville, Hovilehto Seppo, Kirsi Anne, Mustola Seppo, Tiainen Pekka, Toivonen Juhani, Dabnell Sandra, Kaminski Tadeusz, Sysimetsa Anu, Kaukonen Maija, Silvasti Päivi, Vainio Kaisa, Lund Vesa, Sjövall Sari, Saarinen Kari, Viitanen Matti, Ahonen Tommi, Alaspää Ari, Zittling Ritva, Saarinen Aarne, Moisander Annette, Wagner Bodo, Laru-Sompa Raili, Elomaa Esa, Lavonen Leena, Nevantaus Juha, Geier Klau, Kavasmaa Tomi, Koorits Ursula, Kubjas Mare, Lauritsalo Seppo, Ottelin Lauri, Palve Markki, Pynnönen Jari, Rääbis Inga, Saarelainen Minna, Heikkilä Tapani, Kontula Timo, Lehtimäki Markku, Liimatainen Jari, Moilanen-Oikarinen Mari, Pakarinen Marika, Palanne Riku, Seppänen Hanna, Pulkkinen Anni, Vääräniemi Heikki, Koskenkari Juha, Sälkiö Sinikka, Vakkala Merja, Koskue Talvikki, Loisa Pekka, Laitio Ruut, Hautamäki Raku, Koivisto Simo-Pekka, Futier Emmanuel, Lefrant Jean-Yve, Leon Alain, Bonnet Franci, Marret Emmanuel, Spielvogel Catherine, Papageorgiou Chryssa, Szymkiewicz Olga, Tounou-Akue Felix, Aubrun Frederic, Bonnet Aurélie, Gazon Mathieu, Guiraud Michel, Laurent Virginie, Tachon Guillaume, Demars Nadège, Dumenil Anne-Sylvie, Mercier Frederic, Landais Alain, Mentec Herve, Bazin Marie, Gonnu Sophie, Petit Antoine, Albaladejo Pierre, Almeras Luc, Bataillard Amélie, Rossi-Blancher Marine, Yves Lefrant Jean, Barthel Florian, Hallel Dan, Sbai Hicham, Khalifeh Pamela, Lidzborski Lionel, Jully Marion, Platon Ecaterina, Pottecher Julien, Baumgarten Romain, Schultz Christel, Elmiloudi Fayçal, Lefebvre Julie, Waton Karen, Sprunck Adrien, Steib Annick, Thibaud Adrien, Thuet Vincent, Kieffer Vianney, Dubois-Vallaud Delphine, Jacob Laurent, Becanne Xavier, Cherfaoui Salim, Gauzit Remy, Godier Anne, Lakhdari Mourad, Samma Charle, Bigeon Jean-Yve, Burtin Philippe, Halchini Constantin, Lacroix Magali, Pinna Frederic, Barbes Aurélie, Just Bernard, Mateu Philippe, Benayoun Laurent, Berger Philippe, Granier Nathalie, Francois Perrigault Pierre, Libert Nicola, De Rudnicki Stephan, Merat Stéphane, Bourdet Benoit, Ferré Fabrice, Minville Vincent, Piriou Vincent, Rague Philippe, Wallet Florent, Lebuffe Gille, Desbordes Jacque, Robin Emmanuel, Ichai Carole, Orban Jean-Christophe, Marx Gernot, Sander Michael, Gottschalk André, Piontek André, Unterberg Matthia, Hilpert Justu, Kees Martin, Triltsch Andrea, Wiegand-Löhnert Carola, Glöckner Christiane, Hohn Andrea, Rose Elmar, Schröder Stefan, Wiese Oliver, Ramminger Axel, Dresden Caru, de Abreu Marcelo Gama, Heller Axel, Marx Christine, Neidel Julia, Goldmann Anton, von Heymann Christian, Laetsch Beatrix, Maahs Esther, Scholz Lar, Frenzel Dirk, Massarat Kyro, Lenhart Franz-Peter, Reichle Florian, Rudlof Kristina, Borchers Friedrich, Buettner Christoph, Schmutzler Martin, Burgard Gerald, Lucht Alexander, Wagner Jan, Pilge Stefanie, Schneider Gerhard, Untergehrer Gisela, Bis Beata, Krassler Jen, Dittmann Jan, Haberkorn Jörg, Eberitsch Jürgen, Eberitsch Karola, Nippraschk Thoma, Wepler Ulrich, Engelen Wolf-Christian, Nau Carla, Scholler Axel, Schüttler Jürgen, Wintzheimer Simone, Bloos Frank, Braune Anke, Fergen Daniela, Ludewig Katrin, Paxian Marku, Reinhart Konrad, Graf Nikolau, Schwarzkopf Konrad, Berger Katharina, Habicher Marit, Kasperiunaite Ruta, Savelsberg Sabine, Krep Henning, Reindl Michael, Weber Matthia, Bauer Wolfgang, Bingold Florian, Christ Saskia, Friederich Patrick, Kaviani Reza, Auer Patrick, Bonnländer Georg, Drescher Jürgen, Braun Roland, Eichenauer Tim, Kerner John, Bierbaum Kathrin, Brünner Horst, Grond Stefan, Perez-Platz Ursula, Andresen Bent, Linstedt Ulf, Stegmann Nil, Erkens Uwe, Kopcke Jen, Meyer Andrea, Brestrich Hartmut, Ernst Sandra, Merkel Stella, Krieger Lena, Luers Frank, Weyland Andrea, Noeldge-Schomburg Gabriele, Menckie Thoma, Wasmund Christina, Bredtmann Ralph-Dieter, Erler Ine, Raufhake Carsten, Haumann Christine, Möllemann Angela, Oehmichen Uwe, Sergejewa Olga, Lehning Brigitte, Czeslick Elke, Geyer Michaela, Malcharek Michael, Sablotzki Armin, Stier Marina, Feld Florian, Rossaint Rolf, Simon Verena, Armaganidis Apostolo, Koulenti Despoina, Kotanidou Anastasia, Nanas Serafim, Papastylianou Androula, Psevdi Aikaterini, Stathopoulos Anastasio, Voulas Asklepieion, Kanna Efthymia, Koutsikou Anastasia, Moustaka Alexandra, Chovas Achillea, Komnos Apostolo, Zafiridis Tilemacho, Franses Josef, Lavrentieva Athena, Koraki Eleni, Katsenos Chrysostomo, Flora Kasianidou Maria, Nasopoulou Pantelia, Spyropoulou Eleni, Gousia Chrysoula, Katsanoulas Constantine, Lathyris Dimitrio, Kyriazopoulos George, Sfyras Dimitrio, Tsirogianni Athanasia, Kostopanagiotou Georgia, Lignos Mihail, Matsota Paraskevi, Christopoulos Christo, Mouratidou Alexandra, Vrettou Efstratia, Boufidis Spyro, Moka Eleni, Arnaoutoglou Eleni, Koulouras Vasileio, Nakos George, Papathanakos Georgio, Anthopoulos Georgio, Choutas Georgio, Karapanos Dimitrio, Tzani Vaso, Gkiokas Georgio, Nastos Konstantino, Nikolakopoulos Fotio, Dragoumanis Christo, Nikitidis Niko, Pneumatikos Ioanni, Theodorou Vassiliki, Zacharouli Danai, Kandi Stella, Tasopoulos Konstantino, Arvaniti Kostoula, Matamis Dimitrio, Mplougoura Eva, Petropoulou Polixeni, Soumpasis Ioanni, Amaniti Ekaterini, Giannakou-Peftoulidou Maria, Gkeka Eleni, Soultati Ioanna, Kokinou Maria, Papatheodorou Lambrini, Stafylaraki Maria, Giasnetsova Tatiana, Gritsi-Gerogianni Nikoleta, Kydona Christina, Kiskira Olga, Koulentis Ioanni, Apsokardos Alexandro, Dimitropoulos Konstantino, Soldatou Ourania, Nathanail Christodoulo, Papazotos Alexio, Tsakas Pirro, Clouva-Molyvdas Phyllis-Maria, Kolotoura Athina, Sartzi Monika, Papanikolaou Spiro, Polakis Pavlo, Karatzas Styliano, Kyparissi Aikaterini, Papavasilopoulou Theonymfi, Koukoubani Triantafillia, Mastora Evangelia, Spyropoulou-Pagdatoglou Kyriaki, Nyktari Vasileia, Malliotakis Polychroni, Papaioannou Alexandra, Bekos Vasileio, Maragkou Elisavet, Spring Anna, Evagelatos Stavro, Ioakeimidou Aikaterini, Noulas Niko, Molnár Zsolt, Csüllög Emese, Elekes Eniko, Molnár Tamá, Katona Zsuzsana, Kremer Ildiko, Miko Angela, Csomos Ako, Galambos Zsuzsanna, Szucs Ako, Nyikos Gyorgy, Szekeres Gabor, Szabo Ervin, Kranitz Katalin, Simon Melinda, Szigeti Jano, Gaál Emánuel, Havas Attila, Ille Alexandru, Bráz Krisztina, Nagy Geza, Sigurdsson Gisli, Sigurbjörnsson Fridrik T., Sigurdsson Gisli H., Kárason Sigurbergur, Edda Sigurdardottir Elin, Blöndal Ásbjörn, Gunnarsson Björn, Westbrook Andrew, Broderick Alan, Hafeez Parvaiz, Hanumanthaiah Deepak, Brohan Janette, O'Chroinin Donal, Bailey Kevin, Ramamoorthy Karthik, Doyle Yvonne, Freir Noelle, O'Rourke Jame, Jonson Philip, Saeed Sabir, Hayes Ivan, Loughrey John, Frohlich Stephen, Mccauley Nuala, Ryan Donal, Fitzpatrick Gerry, Kevin Leo, Thomas Jubil, Warde Barry, Woolhead Alan, Duggan Michelle, Egan Cara, Crowley Seamu, Lebese Soloman, Bergin Anne, Page Rory, Collins Daniel, Mckenny Michael, Della Rocca Giorgio, Grasso Salvatore, Bresciani Anna, Carmino Livio, Ghelfi Silvia, Lorenzelli Laura, Teresa Novelli Maria, Pescarmona Chiara, Roasio Agostino, Gatta Alessandro, Nastasi Mauro, Sanseverino Manlio, Tinti Carla, Bianchin Andrea, Tormena Maria, Franco Antonio, Marini Federica, Di Mauro Piero, Rapido Francesca, Tommasino Concezione, Bellotti Ferdinando, Boninsegna Daniele, Castellani Gianluca, Sances Daniele, Spano Gianluca, Tredici Stefano, Vezzoli Dario, Fucecchio Igneo, Bacci Alessandro, Coppini Roberta, Dell'Unto Sandro, Mori Emanuele, Rosa Stanzani Maria, Tosi Monica, Collareta Michele, Forfori Francesco, Franchi Matteo, Mancino Giuseppe, Battistella Massimo, Baricocchi Elisa, Bona Francesco, Debernardi Felicino, Giacoletto Gianmarco, Iacobellis Antonio, Massucco Paolo, Moselli Nora, Muratore Andrea, Palomba Graziella, Sardo Elena, De Simone Michele, Suita Luisa, Zocca Edoardo, Bucci Barbara, Della Corte Francesco, Piciucco Tiziana, Viarengo Valeria, Bettelli Gabriella, Cantarini Eugenia, Giampieri Marina, Tanfani Alessandra, Recchia Eugenio, Bignami Elena, Bruno Giovanna, Costagliola Roberto, Gandolfi Azzurra, Greco Massimiliano, Lembo Rosalba, Monti Giacomo, Nicelli Elisa, Pasculli Nicola, Turi Stefano, Baroselli Antonio, Brazzoni Marcella, Buttazzoni Mattia, Buttera Stefania, Centonze Carlo, Serena Giovanni, Spagnesi Lorenzo, Toretti Ilaria, Vilardi Anna, Zearo Ester, Arpino Ine, Baraldi Sara, Guarnerio Chiara, Molene Vincenzo, Concetta Monea Maria, Vaccarisi Enrico, Vicari Luigi, Albante Alida, Aversano Marco, Loiacono Cinzia, Marandola Maurizio, Fusari Maurizio, Petrucci Nicola, Galla Amerigo, Mascia Antonio, Primieri Paolo, Di Noto Anna, Gratarola Angelo, Molin Alessandro, Spagnolo Luigi, Spena Claudio, Calligaro Plinio, Marchiotto Simonetta, Merlini Alberto, Pedrazzoli Eleonora, Perina Giulia, Visentin Renea, Fumagalli Roberto, Garbagnati Andrea, Manetti Bruna, Snaier Chiara, Somaini Marta, Farnia Antonio, Nani Roberto, Pierantonio Novello, De Michele Michele, Gazzanelli Sergio, Pugliese Francesco, Ruberto Franco, Bergamini Elena, Tassinati Tania, Capuzzo Maurizia, Cirillo Vera, Tufano Rosalba, Oggioni Roberto, Parrini Vieri, Brunori Emanuela, Capone Micaela, Carbone Luigi, Corradetti Francesco, Elisei Daniele, Fiorentino Stefano, Francesconi Maurizio, Gattari Diego, Gorgoglione Maria, Lacobone Emanuele, Minnucci Francesco, Montironi Claudio, Riccioni Gianrenato, Tappata Giuseppe, Zompanti Valeria, Verdenelli Paola, Cerutti Elisabetta, Ranieri Vito Marco, Golubovska Iveta, Grigorjevs Sergej, Rikmane Maija, Rozkalne Daina, Stepanovs Jevgenij, Suba Oleg, Kazune Sigita, Miscuk Aleksej, Nemme Jani, Oss Peteri, Sipylaite Jurate, Macas Andriu, Ragaisis Vytauta, Kontrimaviciute Egle, Tomkute Gabija, Boerma Christiaan, Fleur Kramer Irene, Poeze Martijn, Maria John, Pelzer Gerardu, Winsser Lex, Nijsten Maarten, Schoorl Michiel, Spanjersberg Rob, Buhre Wolfgang, Dieleman Stefan, van Klei Wilton, Bouw Martijn, Pickkers Peter, van der Marieke A., Schreiner Frodo, Zandvliet Ria, van den Berg Roy, De Wit Esther, Keijzer Christaan, Hollmann Marku, Preckel Benedikt, van Acker Gij, Dennesen Paul, Veld Ba, Kuijpers-Visser Agne, Inan T., Koopman-van Gemert A., Ponssen Huibert, Brouwer Tammo, Koopmans Matty, van Bommel Jasper, van Duijn Ditty, van der Hoven Ben, Ormskerk Patricia, Beck Oliver, Schiere Sjouke, Reidinga Auke, Venema Allart, Hoogendoorn Marga, Olthof Kee, Flaatten Han, Jammer Ib, Dokka Vegard, Arne Monsen Svein, Marius Ytrebo Lar, Noursadeghi Mostafa, Shahzad Ahmed, Dagfinn Boksasp Ola, Roiss Christoph, Frank Strietzel Han, Gina Anne, Berntsen Schie, Haugland Helge, Ove Vingsnes Svein, Axelsson Patric, Risom Olsen Thoma, Katre Sanjay, Aakeroey Kristin, Mikstacki Adam, Tamowicz Barbara, Boziłow Dominika, Goch Robert, Grabowski Piotr, Kupisiak Jacek, Małłek Małgorzata, Szyca Robert, Kostyrka Włodzimierz, Choma Robert, Jankowski Grzegorz, Kościelniak Władysław, Pietraszek Paweł, Szarowar Bartosz, Matos Ricardo, França Carlo, Pais Lacerda António, Ormonde Lucindo, Rosa Rosário, Pereira Inê, Vitor Paula, Completo Bento Henrique, Raquel Lopes Maria, Carvalho Marque, Faria Manuela, Cláudia de Sousa Ana, de Freitas Pereira, Almeida Eduardo, Mealha Rui, Vicente Rachel, Monte Raquel, Rua Fernando, Barros Nelson, Esteves Francisco, Gouveia Pinheiro Célia Maria, Real Vila, Miguel Oliveira Vítor, Fátima Oliveira Maria, Martins Isabel, Pedro Saraiva José, Pedro Assunção José, Bártolo Anabela, Carvalho Anabela, Correia Carlo, Martins Salomé, Milheiro Ruth, Diaz Alejandro, Imelda Gonçalves Maria, Ribeiro Rosa, Estilita Joana, Glória Carlo, de Almeida José, Barros Filipa, Ramos Armindo, Camara Margarida, Richard Maul Edward, Nobrega Julio, Langner Anuscka, Faria Maia Dionísio, Afonso Ofélia, Faria Filomena, Serra Sofia, Manuela Botelho Maria, Ferreira Pedro, Mourão Luí, Vintém Oliveira Ana, Resende Margarida, Aleman Miguel, Fonseca Jorge, Isidoro Marta, de Meneses Helena, Pêgas António, Pereira José, Pereira Lui, Ramos Bárbara, Matos Francisco, Gonçalves Castro Maria de Lurde, Martins Ana, Ramos Cristina, de Sousa Manuel, Bento Luí, Botas Conceição, Lopes Vitor, Mendes Rosa, Grigoras Ioana, Blaj Mihaela, Damian Mihaela, Lupusoru Andreea, Ristescu Irina, Codreanu Monica, Diaconescu Ciresica, Nistor Alina, Stanescu Stelian Dorin, Streanga Livia, Berneanu Maria, Bordeianu Cristina, Florenta Calarasu, Iacob Alina, Nicoleta Lupu Mary, Mocanu Iulian, Moraru Coca, Meran Carleta, Nicolae Bacalbasa, Sandu Madalina, Turcanu Roxana, Epure Florina, Grigore Monica, Hotaranu Cristina, Popescu Nicoleta, Baban Oleg, Baciu Manuela, Ciobanu Aurica, Ioan Denciu Catalin, Gurau Vitalie, Maftei Ion, Moldovan Ion, Ungureanu Liviu, Bogdan Prodan, Corneci Dan, Dinu Melania, Madalina Dutu, Rely Manolescu, Silvius Negoita, Tomescu Dana, Gabriela Droc, Adrian Dinescu Stelian, Calin Mitre, Ionescu Daniela, Margarit Simona, Vasian Horatiu, Albu Corina, Balasa Carmen, Cadrigati Alina, Dragulescu Dorian, Gavra Loredana, Hentia Ciprian, Macarie Claudiu, Manescu Mihaela, Nediglea Ioan, Ocica Dana, Ovidiu Bedreag, Papurica Mariu, Plavat Cosmin, Popa Claudia, Ramneantu Mihaela, Sandesc Dorel, Sandici Zoran, Sarandan Mihaela, Belciu Ioana, Tincu Eugen, Ursu Irina, Aignatoaie Mariana, Huzuneanu Mariana, Cocu Simona, Hagau Natalia, Ciubotaru Roxana, Copotoiu Sanda-Maria, Copotoiu Ruxandra, Ioana Ghitescu, Kovacs Judit, Leonard Azamfirei, Szederjesi Iano, Genoveva Vanvu, Mosnegutu Simona, Surbatovic Maja, Djordjevic Dragan, Djordjevic Biljana, Grujic Krasimirka, Jovanovic Dusko, Krstic-Lecic Ivana, Obradovic Jovana, Zeba Snjezana, Jevdjic Jasna, Miletic Milo, Zunic Filip, Bulasevic Aleksandra, Brko Radoslava, Gazibegovic Narcisa, Kendrisic Mirjana, Vojinovic Radisa, Firment Jozef, Zahorec Roman, Capková Judita, Grochova Monika, 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López-Cuervo Juan, López Mikel Celaya, Ramírez Alejandro, José Saldaña Francisco, Aliste Pilar, Hermira Anchuelo Ana, García Campos Ascensión, Catalán Mercede, García Gómez Mónica, Gonzalez Gonzalaez Olga, López López Eloísa, Real Navacerrada Isabel, de Quevedo Sara Arlanzón, Gonzalez Serrano Matilde, Silvestre Francisco Perez-Cerdá, Martinez Torrente Francisco, Arocas Blanca, Pastor Martinez Ernesto, Soro Marina, Maroto Fernando, Robledo Algarra Ruth, Silla Aleixandre Iné, Argente Gemma Rodriguez, Lleó Ana Broseta, Rubio Antonio Vela, Vicente Sánchez José Lui, Enríquez Valcárcel Irene, Balust Clara, Balust Jaume, Borrat Xavier, Jose Carretero Maria, Gracia Isabel, Matute Purificacion, Mercadal Jordi, Pujol Roger, Tena Beatriz, Ubre Marta, Dorda Albalad Dolore, Muñoz Alcaide Concepción, Caballero Jesu, Camps Cervantes Angel, de Nadal Clanchet Miriam, Montferrer Estruch Nuria, Ballvé Ferrer Mercè, Lacasta Fornells Albert, Terrer Galera Eduard, Garcia Martinez Irene, Manrique Muñoz Susana, Pelavski Andre, Tormos Perez Pilar, Gonzalez Posada Miguel Angel, de Prat Ivette Chocron, Rello Jordi, García Serrano Llum, Naya Sieiro José Manuel, Silva Lorena, Colomina Sole Maria Jose, Biarnes Suñé Alfon, Rochera Villach Isabel, Gómez Herreras José Ignacio, Poves Rodrigo, Martinez Rafael Beatriz, Martinez Almeida Icier, Fernandez Collates Angel, Jose Bartolomé Maria, Cimadevilla Bonifacio, González González Antonio Manuel, Rabanal Llevot Jose Manuel, de Terán Mira Juan Carlos Diaz, González Molina Begoña, Pardo Sara, López Sánchez Carlo, Williams Monica, Zaldibar Estibaliz, Muñoz Corsini Lourde, Rodríguez Fraile José Ramón, de la Lastra Maria, Kabiri Sacramento Monir, López Saña Francisco Javier, Trenado Ålvarez Josep, Cantón Bulnes Maria Luisa, Gándara Carrasco Violeta, Crespo Ma del Rocío Míguez, Narváez Cubillos Diana, Laza Laza Enrique, Pérez Ma del Pino Heredia, Arenzana Seisdedos Ángel, Fernández Torres Bartolomé, Santos Ampuero Marian, Chicot Llano Marta, Mata Esperanza, Munoz Manuel, Orts Mar, Planas Antonio, Ramasco Fernando, Roman Carlo, Varela Durán Marina, Fernandez Sabela del Río, Sanduende Otero Yolanda, Lopez Pineiro Susana, Barreiro Pardal Cristina, Fernández Alcantud Jesú, Ayuso Antolinos Mercede, Barrios Francisco, Collantes Casanova Ana, Ruiz Castro Manuel, Infantes Crespo Beatriz, Lancha Felipe Uzuri, Liceras Fuster Marta, Sanz García Máximo, Herrero Garrote Begoña, Moreno Gonzalez Ricardo, Montes Granero Maria José, de la Guía Carlos Lloreda, Chaves López Raquel, de Frutos López Santiago, Marco Martinez Jose Javier, Garcia Mostaza Angel, Jiménez Moreno Antonio, Riquelme Osado Irene, Bardina Pastor Ana, Peña Rosa, Rustarazo Pérez Mónica, Aliaño Piña María, Aranda Romero Carlo, Rodríguez Elena Rodríguez, Pedroviejo Sáez Vicente, Safatle Fernando, Hernández Salvan Javier, Galán Sampedro Mar, de la Torre Patricia Alfaro, Pérez Toro Jonatan, Lasa Unzúe Crsitina, José Vargas Maria, Garcia Bernal David, Echevarria Mercede, Ubeda Iglesias Alejandro, Loza Ana, Rodriguez Morillo Araceli, Diaz Serrano Pedro, Barrientos Sevilla Fernando Caba, Cacho Elena, Calderón Ricardo, Dufur Mercede, Marginet Carolina, Monedero Pablo, José Yepes Maria, Rellán Alvarez Luzdivina, Fernández Carballal Francisca, Pensado Castiñeiras Alberto, Dieguez García Paula, Ramos López Lorena, Rama Maceiras Pablo, Martínez Puente María Socorro, Rey Rilo Maria Teresa, Trujillo Alonso Ana Esther, Rodríguez Fernández Sonia, Omaña García Rafael, Pérez García Aníbal, Bello Puentes Rafael, Nunez Aguado Domingo, Lopez Carballo Carlo, Fernandez Fernandez Ricardo, Toledo Presedo Amadeo, de Rabago Ricardo Bermejo Diaz, Rodriguez Velasco Ana, Jiménez Capel Yolanda, Fernández Cortés Ana, Martínez García Esther, Martinez Gimeno Laura, Klamburg Jordi, Castillo Omedas Rosa, González Núñez Miriam, Llubià Maristany Clara, Moret Ruiz Enrique, Artigas Xavier, Castrillón Sebastian, Espinosa Nieve, Gomez-Caro Ana M., Illa Susana, India Inmaculada, Martín-Huerta 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Alvaro, Terol Alvaro de la Vega, Candela Toha Angel, Alvarez Utrera Fernando, Alberdi Fermín, Elósegui Itxaso, García Javier, Marco Garde Pilar, Itziar Mintegui Escudero, García Sáez Iker, Salas Estibaliz, Zabarte Mercede, Diaz-Boladeras Rosa-Maria, Mora-Guevara Emilio, Ferreras Zamora Julia, Bonet Alfon, Salo Lidia, Salinas Unai, Zaballos Juan, Abella Alvarez Ana, Jimenez Garrido Carlo, Hita Roa Juan Ramón, Gordo Vidal Federico, Garcia-Egea Jorge, Zamora Elson Monica, Seron-Arbeloa Carlo, Mendiola Asensio Miguel Angel, Gastaldo Simeón Rosa, Muñoz Alameda Luis Enrique, Oeding Angulo Guillermo, Aranzubia Monserrat, Juan Arcas Jose, Arevalo Julian, Quesada Belvert Belén, Pérez Calvo César, Cremades Marta, Crespo Pascual, Cuarental Ana, Del Olmo Mercede, Turrión Fernández Pablo, Garcia Vega José Luis Franqueza García Isabel, Herrera Elena, Alcala Llorente Miguel Angel, Martin Rabes Cecilia, de Maeyer Ana Gamo, Pérez Marquez Manuel, López Mendoza Diego, Milicua Muñoz José María, Arias Martínez Natividad, Santos Oviedo Arnoldo, Benavent Garrigues Pau, Alonso Íñigo José, Tormo Ferrandiz Sergi, Sanchez-Morcillo Silvia, Lafuente Sánchez Matilde, Marqués Parra Asunción, Gomar Vidal Sonia, Montoiro Allué Raquel, Zalba Etayo Begoña, Bustamante Rodriguez Raquel, Martin Villen Lui, Molla Jimenez Cristina, de Zayas Ricardo Sala, Dolera Moreno Cristina, SanJose Pacheco Fernando, Anton Pascual Jose Lui, Tejera Gude Fernando, Manteiga Riestra Eva, Cota Delgado Francisco, de la Torre Prados Maria Victoria, Barrios Javier, Cervera-Montes Manuel, García-Sanz Mercede, García Vicente, Sanmiguel Guillermo, López Álvaro Julian, Bornay Barrachima Beatriz, Romero Bermejo Francisco Jose, Martinez Garcia Alberto Garcia Fernandez Pilar, Navarro Ramírez Carolina, Gómez Ramos Jorge, Angel Samaniego Lui, Belenguer-Muncharaz Alberto, Ferrándiz-Selles Amparo, Mateu-Campos Maria-Lidon, Domínguez David, Espinosa Elena, León Teresa, Ojeda Betancor Nazario, Garcia Cortes Javier, Díaz Díaz Juan José, Manzano Canalechevarria Ana, Fores Novales Beatriz, Garcia Peña Jose Manuel, Rodriguez Delgado Toma, Santamaria Roquerio Beatriz, Gomez Sainz Juan Jose, Tebar Soto Teresa, Chew Michelle, Seeman-Lodding Heléne, Dahm Peter, Odenstedt Hergès Helena, Lundborg Christoffer, Söndergaard Sören, Rylander Christian, Sari Ferenc, Oscarsson Tibblin Anna, Adolfsson Anne, Klarin Bengt, Schrey Susann, Merisson Edyta, Rydén Jörgen, Britt Divander Mona, Hedin Annika, Hedlund Daniel, Axelsson Lindkvist Mikael, Jawad Monir, Layous Lona, Wernerman Jan, Björne Håkan, Brattström Olof, Olheden Staffan, Oldner Ander, Sellden Eva, Walder Bernhard, Wickboldt Nadine, Rossi Ariane, Steiner Luziu, Djurdjevic Mirjana, Lussmann Roger, Geisen Martin, Hofer Christoph, Turina Matthia, Grocott Mike, Goldhill David, Everett Lynn, Harris Katy, Wright Maggie, Adams David, Alderson Lorraine, Baker Julie, Christie Iain, Ferguson Colin, Hill Matthew, Holmes Kate, Hutton Andrew, Minto Gary, Moor Paul, Porter Andrew, Struthers 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d'anesthésiologie, Surgery, and RS: NUTRIM - R2 - Gut-liver homeostasis

Subjects
Male, The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients, Hospital admission, Hospital discharge, Intensive care, Length of stay, Surgical mortality, Epidemiology, Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7], surgery, Cohort Studies, Clinical endpoint, Medicine, Hospital Mortality, Hospital discharge, education.field_of_study, Mortality rate, Medicine (all), Confounding, General Medicine, Middle Aged, Surgical mortality, Operative, Europe, Hospitalization, Treatment Outcome, Surgical Procedures, Operative, outcomes, surgery, mortality, Female, mortality, cohort study, Cohort study, Human, Adult, medicine.medical_specialty, Critical Care, Population, MEDLINE, Settore MED/41 - ANESTESIOLOGIA, Humans, ddc:610, Mortality, education, surgery, mortality, Europe, Aged, Postoperative Care, Surgical Procedures, business.industry, Length of Stay, Hospital admission, Surgery, Clinical outcomes, Intensive care, Mann–Whitney U test, Cohort Studie, business
Abstract

Item does not contain fulltext BACKGROUND: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe. METHODS: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used chi(2) and Fisher's exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p

Published
2012

50. The transplanted liver graft is capable of clearing asymmetric dimethylarginine.

Author

Siroen MP, Warlé MC, Teerlink T, Nijveldt RJ, Kuipers EJ, Metselaar HJ, Tilanus HW, Kuik DJ, van der Sijp JR, Meijer S, van der Hoven B, and van Leeuwen PA

Subjects
Acute Disease, Arginine blood, Biomarkers blood, Case-Control Studies, Chronic Disease, Graft Rejection blood, Humans, Kidney physiopathology, Liver physiopathology, Liver Failure blood, Osmolar Concentration, Postoperative Period, Prospective Studies, Arginine analogs & derivatives, Arginine metabolism, Liver metabolism, Liver Transplantation
Abstract

Asymmetric dimethylarginine (ADMA) has been recognized as an endogenous inhibitor of the arginine-nitric oxide (NO) pathway. Its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. Considering the liver as a crucial organ in the clearing of ADMA, we hypothesized increased ADMA levels during hepatic failure and, consequently, a decline of ADMA concentrations after successful liver transplantation. The aim of the present study was to investigate the role of the liver in the metabolism of ADMA in patients undergoing liver transplantation. In this prospective study, we investigated the course of ADMA concentrations in 42 patients undergoing liver transplantation and results showed that preoperative ADMA concentrations were higher in patients with acute (1.26 micromol/L, P < .001) and in patients with chronic (.69 micromol/L, P < .001) hepatic failure compared with healthy volunteers (.41 micromol/L). In addition, ADMA concentrations decreased from the preoperative day to the first postoperative day in both the acute (Delta(ADMA): -.63 micromol/L, P = .005) and the chronic hepatic failure group (Delta(ADMA): -0.15 micromol/L, P < .001). Furthermore, in patients who experienced acute rejection, ADMA concentrations were higher during the whole first postoperative month compared with nonrejectors (P = .012). Moreover, in 11 of 13 rejectors (85%) a clear increase in ADMA concentration preceded the onset of the first episode of rejection, which was confirmed by liver biopsy. In conclusion, our results indicate that the transplanted liver graft is quickly capable of clearing ADMA, suggesting preservation of DDAH. In addition, increased ADMA concentrations in the posttransplantation period reflect serious dysfunction of the liver graft during acute rejection.

Published
2004
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