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1. Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study

Author: Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, Kander, Thomas, Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, and Kander, Thomas
Abstract: Background Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. Results In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the p
Published: 2024
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2. Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study

Author: Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, Kander, Thomas, Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, and Kander, Thomas
Abstract: Background Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. Results In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the p
Published: 2024
Full Text: View/download PDF

3. Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study

Author: Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, Kander, Thomas, Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, and Kander, Thomas
Abstract: Background Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. Results In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the p
Published: 2024
Full Text: View/download PDF

4. Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study

Author: Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, Kander, Thomas, Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, and Kander, Thomas
Abstract: Background Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. Results In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the p
Published: 2024
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5. Platelet transfusions in adult thrombocytopenic ICU patients:Protocol for a sub-study of the PLOT-ICU cohort

Author: Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Sivula, Mirka, Møller, Morten Hylander, Russell, Lene, Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Sivula, Mirka, Møller, Morten Hylander, and Russell, Lene
Abstract: IntroductionPlatelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia.MethodsThis is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the ‘Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)’. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively.ConclusionsThe outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients., Introduction: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. Methods: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the ‘Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)’. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. Conclusions: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.
Published: 2024

6. Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study

Author: Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, Kander, Thomas, Bjurström, Martin F., Linder, Ylva C., Kjeldsen-Kragh, Jens, Bengtsson, Jesper, and Kander, Thomas
Abstract: Background Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. Results In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the p
Published: 2024
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7. Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain : a systematic review and meta-analysis

Author: Andersson, Emelie, Kander, Thomas, Werner, Mads U., Cho, Joshua H., Kosek, Eva, Flores Bjurström, Martin, Andersson, Emelie, Kander, Thomas, Werner, Mads U., Cho, Joshua H., Kosek, Eva, and Flores Bjurström, Martin
Abstract: Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction >= 30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.
Published: 2023
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8. Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis.

Author: Andersson, Emelie, Andersson, Emelie, Kander, Thomas, Werner, Mads U, Cho, Joshua H, Kosek, Eva, Bjurström, Martin F, Andersson, Emelie, Andersson, Emelie, Kander, Thomas, Werner, Mads U, Cho, Joshua H, Kosek, Eva, and Bjurström, Martin F
Abstract: Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction ≥30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.
Published: 2023

9. Thrombocytopenia and platelet transfusions in ICU patients:an international inception cohort study (PLOT-ICU)

Author: Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Costa, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, Russell, Lene, Khalil, Ahmed, Yehia, Ahmed, Salem, Haney, Farahat, Hesham, Sudevan, Manu, Biggart, Melissa, Fatima, Nirmeen, Elkhonezy, Mohammed, Bunzel, Anne Marie, Siegumfeldt, Rine M., Vestergaard, Stine R., Pelle, Juliette, Lê, Minh Pierre, Vigneron, Clara, Bertrix, Morgane, Cirera, Paul, Laghlam, Driss, Bredin, Swann, Marin, Nathalie, Toppenberg, Maria, Benelli, Brice, Seguin, Amélie, Garret, Charlotte, Guillotin, Florian, Blonz, Gauthier, Lascarrou, Jean Baptiste, Lemarie, Jérémie, Desmedt, Luc, Agbakou, Maïté, Carpentier, Mathieu, Martin, Maëlle, Benkalfate, Naïla, Zambon, Olivier, Decamps, Paul, Wilquin, Pauline L., Benguerfi, Soraya, Gardner, John, Remor, Natalie, Carr, Sheila, Yang, Gloria, Gernez, Coralie, Thiry, Ingrid, Missri, Louai, Denneborg, Moritz K.G., Brown, Katherine, Casares, Vanessa, Sivula, Mirka, Lappi, Elina, Pettilä, Leena, Heinonen, Jonna, Saario, Minttu, Mecheri, Manal K., Elabbadi, Alezandre, Desnos, Cyrielle, Lafarge, Antoine, Mghirbi, Olfa, Sjøbø, Brit, Christoffersen, Cecilie, Bestle, Frederik H., Lemos, Claudia, Gonçalves, Cristiana V., Jacinto, Nuno M.B., Anselmo, Monica P., Hoeper, Marius M., Hoff, Marja, Simões Freire, Pedro M., Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Costa, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, Russell, Lene, Khalil, Ahmed, Yehia, Ahmed, Salem, Haney, Farahat, Hesham, Sudevan, Manu, Biggart, Melissa, Fatima, Nirmeen, Elkhonezy, Mohammed, Bunzel, Anne Marie, Siegumfeldt, Rine M., Vestergaard, Stine R., Pelle, Juliette, Lê, Minh Pierre, Vigneron, Clara, Bertrix, Morgane, Cirera, Paul, Laghlam, Driss, Bredin, Swann, Marin, Nathalie, Toppenberg, Maria, Benelli, Brice, Seguin, Amélie, Garret, Charlotte, Guillotin, Florian, Blonz, Gauthier, Lascarrou, Jean Baptiste, Lemarie, Jérémie, Desmedt, Luc, Agbakou, Maïté, Carpentier, Mathieu, Martin, Maëlle, Benkalfate, Naïla, Zambon, Olivier, Decamps, Paul, Wilquin, Pauline L., Benguerfi, Soraya, Gardner, John, Remor, Natalie, Carr, Sheila, Yang, Gloria, Gernez, Coralie, Thiry, Ingrid, Missri, Louai, Denneborg, Moritz K.G., Brown, Katherine, Casares, Vanessa, Sivula, Mirka, Lappi, Elina, Pettilä, Leena, Heinonen, Jonna, Saario, Minttu, Mecheri, Manal K., Elabbadi, Alezandre, Desnos, Cyrielle, Lafarge, Antoine, Mghirbi, Olfa, Sjøbø, Brit, Christoffersen, Cecilie, Bestle, Frederik H., Lemos, Claudia, Gonçalves, Cristiana V., Jacinto, Nuno M.B., Anselmo, Monica P., Hoeper, Marius M., Hoff, Marja, and Simões Freire, Pedro M.
Abstract: Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic., Purpose: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
Published: 2023

10. Thrombocytopenia and platelet transfusions in ICU patients:an international inception cohort study (PLOT-ICU)

Author: Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Costa, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, Russell, Lene, Khalil, Ahmed, Yehia, Ahmed, Salem, Haney, Farahat, Hesham, Sudevan, Manu, Biggart, Melissa, Fatima, Nirmeen, Elkhonezy, Mohammed, Bunzel, Anne Marie, Siegumfeldt, Rine M., Vestergaard, Stine R., Pelle, Juliette, Lê, Minh Pierre, Vigneron, Clara, Bertrix, Morgane, Cirera, Paul, Laghlam, Driss, Bredin, Swann, Marin, Nathalie, Toppenberg, Maria, Benelli, Brice, Seguin, Amélie, Garret, Charlotte, Guillotin, Florian, Blonz, Gauthier, Lascarrou, Jean Baptiste, Lemarie, Jérémie, Desmedt, Luc, Agbakou, Maïté, Carpentier, Mathieu, Martin, Maëlle, Benkalfate, Naïla, Zambon, Olivier, Decamps, Paul, Wilquin, Pauline L., Benguerfi, Soraya, Gardner, John, Remor, Natalie, Carr, Sheila, Yang, Gloria, Gernez, Coralie, Thiry, Ingrid, Missri, Louai, Denneborg, Moritz K.G., Brown, Katherine, Casares, Vanessa, Sivula, Mirka, Lappi, Elina, Pettilä, Leena, Heinonen, Jonna, Saario, Minttu, Mecheri, Manal K., Elabbadi, Alezandre, Desnos, Cyrielle, Lafarge, Antoine, Mghirbi, Olfa, Sjøbø, Brit, Christoffersen, Cecilie, Bestle, Frederik H., Lemos, Claudia, Gonçalves, Cristiana V., Jacinto, Nuno M.B., Anselmo, Monica P., Hoeper, Marius M., Hoff, Marja, Simões Freire, Pedro M., Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Póvoa, Pedro, Coelho, Luis, Metaxa, Victoria, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Andreasen, Jo Bønding, Péju, Edwige, Nielsen, Lene Bjerregaard, Hvas, Christine Lodberg, Dufranc, Etienne, Canet, Emmanuel, Lundqvist, Linda, Wright, Christopher John, Schmidt, Julien, Uhel, Fabrice, Ait-Oufella, Hafid, Krag, Mette, Cos Badia, Elisabet, Díaz-Lagares, Cándido, Menat, Sophie, Voiriot, Guillaume, Clausen, Niels Erikstrup, Lorentzen, Kristian, Kvåle, Reidar, Hildebrandt, Thomas, Holten, Aleksander Rygh, Strand, Kristian, Tzalavras, Asterios, Bestle, Morten Heiberg, Klepstad, Pål, Fernandez, Sara, Vimpere, Damien, Costa, Carolina, Graça, Carina, Lueck, Catherina, Juhl, Christian Svendsen, Bådstøløkken, Per Martin, Miranda, Teresa, Lêdo, Lia Susana Aires, Sousa Torres, Joao Carlos, Granholm, Anders, Møller, Morten Hylander, Russell, Lene, Khalil, Ahmed, Yehia, Ahmed, Salem, Haney, Farahat, Hesham, Sudevan, Manu, Biggart, Melissa, Fatima, Nirmeen, Elkhonezy, Mohammed, Bunzel, Anne Marie, Siegumfeldt, Rine M., Vestergaard, Stine R., Pelle, Juliette, Lê, Minh Pierre, Vigneron, Clara, Bertrix, Morgane, Cirera, Paul, Laghlam, Driss, Bredin, Swann, Marin, Nathalie, Toppenberg, Maria, Benelli, Brice, Seguin, Amélie, Garret, Charlotte, Guillotin, Florian, Blonz, Gauthier, Lascarrou, Jean Baptiste, Lemarie, Jérémie, Desmedt, Luc, Agbakou, Maïté, Carpentier, Mathieu, Martin, Maëlle, Benkalfate, Naïla, Zambon, Olivier, Decamps, Paul, Wilquin, Pauline L., Benguerfi, Soraya, Gardner, John, Remor, Natalie, Carr, Sheila, Yang, Gloria, Gernez, Coralie, Thiry, Ingrid, Missri, Louai, Denneborg, Moritz K.G., Brown, Katherine, Casares, Vanessa, Sivula, Mirka, Lappi, Elina, Pettilä, Leena, Heinonen, Jonna, Saario, Minttu, Mecheri, Manal K., Elabbadi, Alezandre, Desnos, Cyrielle, Lafarge, Antoine, Mghirbi, Olfa, Sjøbø, Brit, Christoffersen, Cecilie, Bestle, Frederik H., Lemos, Claudia, Gonçalves, Cristiana V., Jacinto, Nuno M.B., Anselmo, Monica P., Hoeper, Marius M., Hoff, Marja, and Simões Freire, Pedro M.
Abstract: Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic., Purpose: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
Published: 2023

11. ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients.

Author: Kander, Thomas, Bjurstrom, Martin F, Frigyesi, Attila, Jöud, Magnus, Nilsson, Caroline U, Kander, Thomas, Bjurstrom, Martin F, Frigyesi, Attila, Jöud, Magnus, and Nilsson, Caroline U
Abstract: BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.
Published: 2022
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12. Blood compatibility of widely used central venous catheters; an experimental study

Author: Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, Sanchez, Javier, Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, and Sanchez, Javier
Abstract: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.
Published: 2022
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13. Blood compatibility of widely used central venous catheters; an experimental study

Author: Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, Sanchez, Javier, Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, and Sanchez, Javier
Abstract: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.
Published: 2022
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14. Blood compatibility of widely used central venous catheters; an experimental study

Author: Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, Sanchez, Javier, Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, and Sanchez, Javier
Abstract: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.
Published: 2022
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15. Blood compatibility of widely used central venous catheters; an experimental study

Author: Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, Sanchez, Javier, Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, and Sanchez, Javier
Abstract: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.
Published: 2022
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16. Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT-ICU)

Author: Anthon, Carl Thomas, Pene, Frederic, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van de Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hastbacka, Johanna, Moller, Morten Hylander, Russell, Lene, Anthon, Carl Thomas, Pene, Frederic, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van de Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hastbacka, Johanna, Moller, Morten Hylander, and Russell, Lene
Abstract: Introduction Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 x 10(9)/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.
Published: 2022

17. Platelet transfusions and thrombocytopenia in intensive care units:Protocol for an international inception cohort study (PLOT-ICU)

Author: Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Møller, Morten Hylander, Russell, Lene, Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Møller, Morten Hylander, and Russell, Lene
Abstract: Introduction: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.
Published: 2022

18. Platelet transfusions and thrombocytopenia in intensive care units:Protocol for an international inception cohort study (PLOT-ICU)

Author: Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Møller, Morten Hylander, Russell, Lene, Anthon, Carl Thomas, Pène, Frédéric, Perner, Anders, Azoulay, Elie, Puxty, Kathryn, Van De Louw, Andry, Barratt-Due, Andreas, Chawla, Sanjay, Castro, Pedro, Povoa, Pedro, Coelho, Luis, Metaxa, Victoria, Munshi, Laveena, Kochanek, Matthias, Liebregts, Tobias, Kander, Thomas, Hästbacka, Johanna, Møller, Morten Hylander, and Russell, Lene
Abstract: Introduction: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.
Published: 2022

19. Blood compatibility of widely used central venous catheters; an experimental study

Author: Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, Sanchez, Javier, Thorarinsdottir, Hulda, Kander, Thomas, Johansson, Dorota, Nilsson, Bo, Klarin, Bengt, and Sanchez, Javier
Abstract: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.
Published: 2022
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20. Time to peak effect of aspirin-induced platelet inhibition and ex vivo effects of desmopressin: An observational study

Author: Schott, Ulf, Sigurjonsdóttir, Sigurbjörg, Thomas, Owain, Kander, Thomas, Schott, Ulf, Sigurjonsdóttir, Sigurbjörg, Thomas, Owain, and Kander, Thomas
Abstract: Objective: To investigate time to maximal platelet inhibition after an oral loading dose of ASA. The effect of ex vivo reversal platelet inhibition by desmopressin (DDAVP) was also studied. Methods: Ten healthy volunteers were given a 300 mg ASA-tablet. Blood was sampled at 0, 15, 30, 60, 120 and 180 minutes. DDAVP was added to the samples taken at 120 minutes. Samples were analysed with a Multiplate® platelet aggregometer (MEA) using arachidonic acid (AA), collagen and thrombin aggregation agonists. Results: Platelet inhibition was observed in the sample activated by AA at 15 minutes but not until 120 minutes in the samples activated by collagen. No platelet inhibition was seen in the samples activated by thrombin. The median time to maximal AA-induced platelet inhibition of <30 U was 30 (interquartile range 15-90) minutes. Ex vivo DDAVP did not reverse platelet inhibition. Subgroup analysis did not show any gender differences. Conclusions: ASA induces a strong platelet inhibition within 30 minutes of oral ingestion, with no gender differences. Ex vivo DDAVP did not reverse ASA’s platelet inhibition.
Published: 2021

21. Biofilm formation on three different endotracheal tubes : a prospective clinical trial

Author: Thorarinsdottir, Hulda Rosa, Kander, Thomas, Holmberg, Anna H., Petronis, Sarunas, Klarin, Bengt, Thorarinsdottir, Hulda Rosa, Kander, Thomas, Holmberg, Anna H., Petronis, Sarunas, and Klarin, Bengt
Abstract: BACKGROUND: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. METHODS: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. RESULTS: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14-15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06-0.59], p = 0.005, and OR 0.34 [95% CI 0.13-0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17-1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. CONCLUSION: High-grade biofilm formation on ETTs was associated with devel, Export Date: 15 July 2020; Article
Published: 2020
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22. Biofilm formation on three different endotracheal tubes : a prospective clinical trial

Author: Thorarinsdottir, Hulda Rosa, Kander, Thomas, Holmberg, Anna H., Petronis, Sarunas, Klarin, Bengt, Thorarinsdottir, Hulda Rosa, Kander, Thomas, Holmberg, Anna H., Petronis, Sarunas, and Klarin, Bengt
Abstract: BACKGROUND: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. METHODS: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. RESULTS: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14-15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06-0.59], p = 0.005, and OR 0.34 [95% CI 0.13-0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17-1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. CONCLUSION: High-grade biofilm formation on ETTs was associated with devel, Export Date: 15 July 2020; Article
Published: 2020
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23. Synergistic platelet inhibition between Omega-3 and acetylsalicylic acid dose titration; an observational study

Author: Bagger, Harald, Hansson, Mattias, Kander, Thomas, Schott, Ulf, Bagger, Harald, Hansson, Mattias, Kander, Thomas, and Schott, Ulf
Abstract: Background: Omega-3 and acetylsalicylic acid (ASA) are two widely used “over-the-counter” drugs. Previous researchhas shown multiple electrode aggregometry (MEA) can detect ASA and varying Omega-3 platelet inhibiting effects.Synergistic platelet inhibiting effects of ASA and Omega-3 have been found using other methods than MEA. The aimof this study was to investigate the antiplatelet effects of Omega-3, and ASA synergism with MEA.Methods: Ten healthy male volunteers ingested Omega-3 (1260mg/day) for 5 days. MEA was used to analyse plateletfunction before and after Omega-3 intake. Aggregation was initiated using three different agonists and measured asarea under the curve (AUC): adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) andarachidonic acid (ASPI). Two concentrations of ASA were dose titrated ex vivo to 2 out of 3 ASPI test cells in order tomeasure synergism between Omega-3 and ASA.Results: Following 5 days Omega-3 intake, ADP, TRAP and ASPI AUC did not change significantly. In vitro ASA beforeOmega-3 intake, reduced ASPI AUC < 30 U, indicating a strong platelet inhibiting effect. Below this AUC level, the 5 daysOmega-3 intake increased ASPI-AUC with the ex vivo added low dose ASA (P = 0.02) and high dose ASA (P = 0.04).Conclusions: No synergism between ASA and Omega-3 was found using the MEA ASPI test. The surprising increase inASPI-AUC following Omega-3 intake and ex vivo ASA suggest that there are methodological issuses with the MEA ASPI test.
Published: 2020

24. Vitamin K deficiency in critical ill patients; a prospective observational study

Author: Dahlberg, Sofia, Dahlberg, Sofia, Schurgers, Leon, Schott, Ulf, Kander, Thomas, Dahlberg, Sofia, Dahlberg, Sofia, Schurgers, Leon, Schott, Ulf, and Kander, Thomas
Abstract: Background: Vitamin K is a cofactor for proteins involved in cardiovascular health, bone metabolism and cancer. Measuring uncarboxylated prothrombin, also termed as "protein induced by vitamin K absence or antagonism for factor II (PIVKA-II)", has been used to assess vitamin K status. High levels may indicate vitamin K deficiency. The aim of this study was to measure PIVKA-II and prothrombin time (PT-INR) in intensive care (ICU) patients and correlate vitamin K status with mortality. Methods: Ninety-five patients admitted to the ICU had blood samples taken near admission and every third day. In addition to PIVKA-II and PT-INR, critical-care severity scores were computed. Results: The median baseline PIVKA-II was 4.97 mu g/L compared to the upper reference of 2.0 pg/L PIVKA-II further increased at days 3 and 6, (median 7.88 mu g/L, p = .047 and median 8.14 mu g/L, p = .011) predominantly in cardiac arrest patients (median 21.4 mu g/L, day 3). Conclusion: Intensive care patients have increased PIVKA-II levels at admission, which increases during the ICU stay, especially in cardiac arrest patients. There were no correlations between PIVKA-II and PT-INR, SOFA score or mortality. Further studies are needed to determine why PIVKA-II increases and whether high PIVKA-II levels in ICU patients affect long-term mortality or morbidity. (C) 2018 Elsevier Inc. All rights reserved.
Published: 2019

25. Vitamin K deficiency in critical ill patients; a prospective observational study

Author: Dahlberg, Sofia, Schurgers, Leon, Schott, Ulf, Kander, Thomas, Dahlberg, Sofia, Schurgers, Leon, Schott, Ulf, and Kander, Thomas
Abstract: Background: Vitamin K is a cofactor for proteins involved in cardiovascular health, bone metabolism and cancer. Measuring uncarboxylated prothrombin, also termed as "protein induced by vitamin K absence or antagonism for factor II (PIVKA-II)", has been used to assess vitamin K status. High levels may indicate vitamin K deficiency. The aim of this study was to measure PIVKA-II and prothrombin time (PT-INR) in intensive care (ICU) patients and correlate vitamin K status with mortality. Methods: Ninety-five patients admitted to the ICU had blood samples taken near admission and every third day. In addition to PIVKA-II and PT-INR, critical-care severity scores were computed. Results: The median baseline PIVKA-II was 4.97 mu g/L compared to the upper reference of 2.0 pg/L PIVKA-II further increased at days 3 and 6, (median 7.88 mu g/L, p = .047 and median 8.14 mu g/L, p = .011) predominantly in cardiac arrest patients (median 21.4 mu g/L, day 3). Conclusion: Intensive care patients have increased PIVKA-II levels at admission, which increases during the ICU stay, especially in cardiac arrest patients. There were no correlations between PIVKA-II and PT-INR, SOFA score or mortality. Further studies are needed to determine why PIVKA-II increases and whether high PIVKA-II levels in ICU patients affect long-term mortality or morbidity. (C) 2018 Elsevier Inc. All rights reserved.
Published: 2019

26. Effekt av intravenöst givet K-vitamin till kritiskt sjuka patienter med spontant förlängd protrombintid.

Author: Dahlberg, Sofia, Ängeby Eriksson, Emilia, Kander, Thomas, Schott, Ulf, Dahlberg, Sofia, Ängeby Eriksson, Emilia, Kander, Thomas, and Schott, Ulf
Abstract: Studien demonstrerar att protrombintid(PT) och aktivitet av K-vitaminberoende koagulationsfaktorer hos kritiskt sjuka patienter med spontanförlängda PT-värden har förstärkts 24 timmar efter Konakion.
Published: 2019

27. Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study

Author: Madotto, F, Pham, T, Bellani, G, Bos, L, Simonis, F, Fan, E, Artigas, A, Brochard, L, Schultz, M, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, van Haren, F, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Démpaire, G, Sula, H, Nunci, L, Cani, A, Zazu, A, Dellera, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, A, Mataloun, S, Moock, M, Thompson, M, Gonçalves, C, Antônio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, Sales, V, Shindhe, S, Ismail, D, Beloncle, F, Davies, K, Cirone, R, Manoharan, V, Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farías, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreño, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Jimenez, J, Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Máca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, Llano, M, Burtin, P, Buzancais, G, Beuret, P, Pelletier, N, Mortaza, S, Mercat, A, Chelly, J, Jochmans, S, Terzi, N, Daubin, C, Carteaux, G, de Prost, N, Chiche, J, Daviaud, F, Fartoukh, M, Barberet, G, Biehler, J, Dellamonica, J, Doyen, D, Arnal, J, Briquet, A, Hraiech, S, Papazian, L, Roux, D, Messika, J, Kalaitzis, E, Dangers, L, Combes, A, Au, S, Béduneau, G, Carpentier, D, Zogheib, E, Dupont, H, Ricome, S, Santoli, F, Besset, S, Michel, P, Gelée, B, Danin, P, Goubaux, B, Crova, P, Phan, N, Berkelmans, F, Badie, J, Tapponnier, R, Gally, J, Khebbeb, S, Herbrecht, J, Schneider, F, Declercq, P, Rigaud, J, Duranteau, J, Harrois, A, Chabanne, R, Marin, J, Bigot, C, Thibault, S, Ghazi, M, Boukhazna, M, Zein, S, Richecoeur, J, Combaux, D, Grelon, F, Le Moal, C, Sauvadet, E, Robine, A, Lemiale, V, Reuter, D, Dres, M, Demoule, A, Goldgran-Toledano, D, Baboi, L, Guérin, C, Lohner, R, Kraßler, J, Schäfer, S, Zacharowski, K, Meybohm, P, Reske, A, Simon, P, Hopf, H, Schuetz, M, Baltus, T, Papanikolaou, M, Papavasilopoulou, T, Zacharas, G, Ourailogloy, V, Mouloudi, E, Massa, E, Nagy, E, Stamou, E, Kiourtzieva, E, Oikonomou, M, Avila, L, Cortez, C, Citalán, J, Jog, S, Sable, S, Shah, B, Gurjar, M, Baronia, A, Memon, M, Muthuchellappan, R, Ramesh, V, Shenoy, A, Unnikrishnan, R, Dixit, S, Rhayakar, R, Ramakrishnan, N, Bhardwaj, V, Mahto, H, Sagar, S, Palaniswamy, V, Ganesan, D, Jamaati, H, Heidari, F, Meaney, E, Nichol, A, Knapman, K, O’Croinin, D, Dunne, E, Breen, D, Jaafar, R, Dwyer, R, Amir, F, Ajetunmobi, O, O’Muircheartaigh, A, Black, C, Treanor, N, Collins, D, Altaf, W, Zani, G, Fusari, M, Spadaro, S, Volta, C, Graziani, R, Brunettini, B, Palmese, S, Formenti, P, Umbrello, M, Lombardo, A, Pecci, E, Botteri, M, Savioli, M, Protti, A, Mattei, A, Schiavoni, L, Tinnirello, A, Todeschini, M, Giarratano, A, Cortegiani, A, Sher, S, Rossi, A, Antonelli, M, Montini, L, Casalena, P, Scafetti, S, Panarello, G, Occhipinti, G, Patroniti, N, Pozzi, M, Biscione, R, Poli, M, Raimondi, F, Albiero, D, Crapelli, G, Beck, E, Pota, V, Schiavone, V, Molin, A, Tarantino, F, Monti, G, Frati, E, Mirabella, L, Cinnella, G, Fossali, T, Colombo, R, Pattarino, P, Mojoli, F, Braschi, A, Borotto, E, Cracchiolo, A, Palma, D, Raponi, F, Foti, G, Vascotto, E, Coppadoro, A, Brazzi, L, Floris, L, Iotti, G, Venti, A, Yamaguchi, O, Takagi, S, Maeyama, H, Watanabe, E, Yamaji, Y, Shimizu, K, Shiozaki, K, Futami, S, Ryosuke, S, Saito, K, Kameyama, Y, Ueno, K, Izawa, M, Okuda, N, Suzuki, H, Harasawa, T, Nasu, M, Takada, T, Ito, F, Nunomiya, S, Koyama, K, Abe, T, Andoh, K, Kusumoto, K, Hirata, A, Takaba, A, Kimura, H, Matsumoto, S, Higashijima, U, Honda, H, Aoki, N, Imai, H, Ogino, Y, Mizuguchi, I, Ichikado, K, Nitta, K, Mochizuki, K, Hashida, T, Tanaka, H, Nakamura, T, Niimi, D, Ueda, T, Kashiwa, Y, Uchiyama, A, Sabelnikovs, O, Oss, P, Haddad, Y, Liew, K, Ñamendys-Silva, S, Jarquin-Badiola, Y, Sanchez-Hurtado, L, Gomez-Flores, S, Marin, M, Lemus, J, Fierro, J, Cervantes, M, Mejia, F, Dector, D, Gonzalez, D, Estrella, C, Sanchez-Medina, J, Ramirez-Gutierrez, A, George, F, Aguirre, J, Buensuseso, J, Poblano, M, Dendane, T, Balkhi, H, Elkhayari, M, Samkaoui, N, Ezzouine, H, Benslama, A, Amor, M, Maazouzi, W, Cimic, N, Beck, O, Bruns, M, Schouten, J, Rinia, M, Raaijmakers, M, van Wezel, H, Heines, S, Strauch, U, Buise, M, Goodson, J, Browne, T, Navarra, L, Hunt, A, Hutchison, R, Bailey, M, Newby, L, Mcarthur, C, Kalkoff, M, Mcleod, A, Casement, J, Hacking, D, Andersen, F, Dolva, M, Barratt-Due, A, Noremark, K, Søreide, E, Sjøbø, B, Guttormsen, A, Yoshido, H, Aguilar, R, Oscanoa, F, Alisasis, A, Robles, J, Pasanting-Lim, R, Tan, B, Andruszkiewicz, P, Jakubowska, K, Coxo, C, Alvarez, A, Oliveira, B, Montanha, G, Barros, N, Pereira, C, Messias, A, Monteiro, J, Araujo, A, Catorze, N, Marum, S, Bouw, M, Gomes, R, Brito, V, Castro, S, Estilita, J, Barros, F, Serra, I, Martinho, A, Tomescu, D, Marcu, A, Bedreag, O, Papurica, M, Corneci, D, Negoita, S, Grigoriev, E, Gritsan, A, Gazenkampf, A, Almekhlafi, G, Albarrak, M, Mustafa, G, Maghrabi, K, Salahuddin, N, Aisa, T, Jabbary, A, Tabhan, E, Trinidad, O, Dorzi, H, Bolon, S, Smith, O, Mancebo, J, Aguirre-Bermeo, H, Lopez-Delgado, J, Esteve, F, Rialp, G, Forteza, C, de Haro, C, Albaiceta, G, de Cima-Iglesias, S, Seoane-Quiroga, L, Ceniceros-Barros, A, Ruiz-Aguilar, A, Claraco-Vega, 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R, Aisiku, I, Henderson, G, Frendl, G, Hou, S, Owens, R, Schomer, A, Bumbasirevic, V, Jovanovic, B, Surbatovic, M, Veljovic, M, Madotto, Fabiana, Pham, Tài, Bellani, Giacomo, Bos, Lieuwe D., Simonis, Fabienne D., Fan, Eddy, Artigas, Antonio, Brochard, Laurent, Schultz, Marcus J., Laffey, John G., Pesenti, Antonio, Esteban, Andres, Gattinoni, Luciano, van Haren, Frank, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Rubenfeld, Gordon, Thompson, B. Taylor, Wrigge, Hermann, Slutsky, Arthur S., Rios, Fernando, Sottiaux, T., Depuydt, P., Lora, Fredy S., Azevedo, Luciano Cesar, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Matamis, Dimitrios, Ranero, Jorge Luis, Amin, Pravin, Hashemian, S. M., Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M., Laake, Jon Henrik, Palo, Jose Emmanuel, Do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicolas, Lorente, Jose A., Piquilloud, Lise, Abroug, Fekri, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Alejandro, Risso V., Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O., Cardonnet, Luis P., Bettini, Lisandro R., Bisso, Mariano Carboni, Osman, Emilio M., Setten, Mariano G., Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Pozo, Norberto C., Grubissich, Nicolas, Plotnikow, Gustavo A., Vasquez, Daniela N., Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A., Saenz, María G., Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E., Cerrato, Valeria I., Bezzi, Marco G., Borello, Silvina A., Loiacono, Flavia A., Fernandez, Adriana M., Knowles, Serena, Reynolds, Claire, Inskip, Deborah M., Miller, Jennene J., Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J., Millar, Rebecca T., Mckenna, Toni E., Bailey, Irene M., Hanlon, Gabrielle C., Aneman, Anders, Lynch, Joan M., Azad, Raman, Neal, John, Woods, Paul W., Roberts, Brigit L., Kol, Mark R., Wong, Helen S., Riss, Katharina C., Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A., Dive, Alain M., Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I., Beraldo, Daniel O., Piras, Claudio, Rampinelli, Adenilton M., Nassar, Antonio P., Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M., Gonçalves, Claudio H., Antônio, Ana Carolina P., Ascoli, Aline, Biondi, Rodrigo S., Fontenele, Danielle C., Nobrega, Danielle, Sales, Vanessa M., Shindhe, Suresh, Ismail, Dk Maizatul Aiman B. Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G., Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C., Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D., Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R., Garcia, Patricio H., Aliaga, Felipe A., Farías, Pamela A., Yumha, Jacob S., Ortiz, Claudia A., Salas, Javier E., Saez, Alejandro A., Vega, Luis D., Labarca, Eduardo F., Martinez, Felipe T., Carreño, Nicolás G., Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L., Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya, Huang, Xiao B., He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X., Qin, Shu H., Zhu, Bao H., Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L., Zhou, Fa, Li, Qiong J., Zhang, Xing Y., Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N., Zhao, Xian Y., Li, Yuan Y., Li, Xiao L., Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q., Zhu, Wei H., Hang, Ai, Hua, Ma, Li, Yimin, Xu, Yonghao, Di, Yu, Ling, Long L., Qin, Tie H., Wang, Shou H., Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P., Jimenez, Juan I. Silesky, Rojas, Manuel A. González, Solis-Quesada, Jaime E., Ramirez-Alfaro, Christian M., Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G., Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H., Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L., Besset, Sebastien L., Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J., Phan, Nga T., Berkelmans, Frantz, Badie, Julio C., Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M., Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Zein, Salem Ould, Richecoeur, Jack R., Combaux, Daniele M., Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P., Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D., Meybohm, Patrick, Reske, Andreas W., Simon, Philipp, Hopf, Hans-Bernd F., Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N., Papavasilopoulou, Theonymfi G., Zacharas, Giannis A., Ourailogloy, Vasilis, Mouloudi, Eleni K., Massa, Eleni V., Nagy, Eva O., Stamou, Electra E., Kiourtzieva, Ellada V., Oikonomou, Marina A., Avila, Luis E., Cortez, Cesar A., Citalán, Johanna E., Jog, Sameer A., Sable, Safal D., Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K., Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J., Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B., Rhayakar, Rachana V., Ramakrishnan, Nagarajan, Bhardwaj, Vallish K., Mahto, Heera L., Sagar, Sudha V., Palaniswamy, Vijayanand, Ganesan, Deeban, Hashemian, Seyed Mohammadreza, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A., Nichol, Alistair, Knapman, Karl M., O’Croinin, Donall, Dunne, Eimhin S., Breen, Dorothy M., Clarkson, Kevin P., Jaafar, Rola F., Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O., O’Muircheartaigh, Aogan C., Black, Colin S., Treanor, Nuala, Collins, Daniel V., Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A., Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M., Montini, Luca M., Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R., Poli, Michela M., Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Pattarino, Pierpaolo Terragni Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E., Cracchiolo, Andrea N., Palma, Daniela M., Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R., Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A., Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N., Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y., Ñamendys-Silva, Silvio A., Jarquin-Badiola, Yves D., Sanchez-Hurtado, Luis A., Gomez-Flores, Saira S., Marin, Maria C., Villagomez, Asisclo J., Lemus, Jordana S., Fierro, Jonathan M., Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Dector, Dulce, Dector, Dulce M., Gonzalez, Daniel R., Estrella, Claudia R., Sanchez-Medina, Jorge R., Ramirez-Gutierrez, Alvaro, George, Fernando G., Aguirre, Janet S., Buensuseso, Juan A., Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M., Schouten, Jeroen A., Rinia, Myra, Raaijmakers, Monique, van Wezel, Hellen M., Heines, Serge J., Strauch, Ulrich, Buise, Marc P., Goodson, Jennifer C., Browne, Troy S., Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A., Bailey, Mathew B., Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J., Andersen, Finn H., Dolva, Merete S., Laake, Jon H., Barratt-Due, Andreas, Noremark, Kim Andre L., Søreide, Eldar, Sjøbø, Brit Å., Guttormsen, Anne B., Yoshido, Hector H. Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A. Montes, Alisasis, Alain U., Robles, Joanne B., Pasanting-Lim, Rossini Abbie B., Tan, Beatriz C., Andruszkiewicz, Pawel, Jakubowska, Karina, Coxo, Cristina M., Alvarez, António M., Oliveira, Bruno S., Montanha, Gustavo M., Barros, Nelson C., Pereira, Carlos S., Messias, António M., Monteiro, Jorge M., Araujo, Ana M., Catorze, Nuno T., Marum, Susan M., Bouw, Maria J., Gomes, Rui M., Brito, Vania A., Castro, Silvia, Estilita, Joana M., Barros, Filipa M., Serra, Isabel M., Martinho, Aurelia M., Tomescu, Dana R., Marcu, Alexandra, Bedreag, Ovidiu H., Papurica, Marius, Corneci, Dan E., Negoita, Silvius Loan, Grigoriev, Evgeny, Gritsan, Alexey I., Gazenkampf, Andrey A., Almekhlafi, Ghaleb, Albarrak, Mohamad M., Mustafa, Ghanem M., Maghrabi, Khalid A., Salahuddin, Nawal, Aisa, Tharwat M., Jabbary, Ahmed S. Al, Tabhan, Edgardo, Arabi, Yaseen M., Trinidad, Olivia A., Dorzi, Hasan M. Al, Tabhan, Edgardo E., Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C., Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, de Haro, Candelaria, Albaiceta, Guillermo M., de Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L., Claraco-Vega, Luis M., Soler, Juan Alfonso, Del Carmen Lorente, Maria, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B., Perez, Manuel P., Perez, Cesar P., Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C., de Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Ma Teresa, Arizmendi, Alfons, Piacentini, Enrique A., Franco, Nieves, Honrubia, Teresa, Cheng, Meisy Perez, Losada, Elena Perez, Blanco, Javier, Yuste, Luis J., Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G., Alonso, Javier G., Alda, Rosa S., Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Navalpotro, Miguel Angel Blasco, Abad, Ricardo Diaz, González, Raquel Montiel, Toribio, Dácil Parrilla, Castro, Alejandro G., Artiga, Maria Jose D., Penuelas, Oscar, Roser, Tomas P., Olga, Moreno F., Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P., Elisabet, Garcia M., Claverias, Laura, Magret, Monica, Pellicer, Ana M., Rodriguez, Lucia L., Sánchez-Ballesteros, Jesús, González-Salamanca, Ángela, Jimenez, Antonio G., Huerta, Francisco P., Diaz, Juan Carlos J. Sotillo, Lopez, Esther Bermejo, Moya, David D. Llinares, Alfonso, Alec A. Tallet, Luis, Palazon Sanchez Eugenio, Cesar, Palazon Sanchez, Rafael, Sánchez I., Virgilio, Corcoles G., Recio, Noelia N., Adamsson, Richard O., Rylander, Christian C., Holzgraefe, Bernhard, Broman, Lars M., Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lars, Helleberg, Johan, Eriksson, Karin E., Glietsch, Rita, Larsson, Niklas, Nygren, Ingela, Nunes, Silvia L., Morin, Anna-Karin, Kander, Thomas, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Souissi, Asma Ben, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O., Derman, Suleyman S., Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K., Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S., Fawkes, Danielle A., Watt, Philip, Twohey, Linda, Thomas, Rajeev R. Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J., Hormis, Anil P., Kannan, Santhana G., Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolcs, Nutt, Christopher, O’Neill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J., Ellis, Helen E., McKechnie, Stuart, Hutton, Paula J., Di Tomasso, Nora N., Vitale, Michela N., Griffin, Ruth O., Dean, Michael N., Cranshaw, Julius H., Willett, Emma L., Ioannou, Nicholas, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D., Williams, Alexandra J., Boyd, Owen, de Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K., Wenham, Tim, Szakmany, Tamas, Toth-Tarsoly, Piroska, McCalman, Katie H., Alexander, Peter, Stephenson, Lorraine, Collyer, Thomas, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M., Sim, Malcolm, Wrathall, David W., Irvine, Donald A., Zantua, Kim S., Adams, John C., Burtenshaw, Andrew J., Sellors, Gareth P., Welters, Ingeborg D., Williams, Karen E., Hessell, Robert J., Oldroyd, Matthew G., Battle, Ceri E., Pillai, Suresh, Kajtor, Istvan, Sivashanmugavel, Mageswaran, O’Kane, Sinead C., Donnelly, Adrian, Frigyik, Aniko D., Careless, Jon P., May, Martin M., Stewart, Richard, Trinder, T. John, Hagan, Samantha J., Wise, Matt P., Cole, Jade M., MacFie, Caroline C., Dowling, Anna T., Nin, Nicolás, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C., Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M., Beitler, Jeremy R., Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn, John O., Gomaa, Dina, Tainter, Christopher, Yeatts, Dale J., Warren, Jessica, Lanspa, Michael J., Miller, Russel R., Grissom, Colin K., Brown, Samuel M., Bauer, Philippe R., Gosselin, Ryan J., Kitch, Barrett T., Cohen, Jason E., Beegle, Scott H., Gueret, Renaud M., Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G., Lamb, Keith D., Oetting, Trevor W., Mohr, Nicholas M., Judy, Claine, Saito, Shigeki, Kheir, Fayez M., Kheir, Fayez, Schlichting, Adam B., Delsing, Angela, Crouch, Daniel R., Elmasri, Mary, Ismail, Dina, Dreyer, Kyle R., Blakeman, Thomas C., Baron, Rebecca M., Grijalba, Carolina Quintana, Hou, Peter C., Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L., Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Madotto, F, Pham, T, Bellani, G, Bos, L, Simonis, F, Fan, E, Artigas, A, Brochard, L, Schultz, M, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, van Haren, F, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Démpaire, G, Sula, H, Nunci, L, Cani, A, Zazu, A, Dellera, C, 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Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farías, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreño, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Jimenez, J, Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Máca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, Llano, M, Burtin, P, Buzancais, G, Beuret, P, Pelletier, N, Mortaza, S, Mercat, A, Chelly, J, 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Taylor, Wrigge, Hermann, Slutsky, Arthur S., Rios, Fernando, Sottiaux, T., Depuydt, P., Lora, Fredy S., Azevedo, Luciano Cesar, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Matamis, Dimitrios, Ranero, Jorge Luis, Amin, Pravin, Hashemian, S. M., Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M., Laake, Jon Henrik, Palo, Jose Emmanuel, Do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicolas, Lorente, Jose A., Piquilloud, Lise, Abroug, Fekri, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Alejandro, Risso V., Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O., Cardonnet, Luis P., Bettini, Lisandro R., Bisso, Mariano Carboni, Osman, Emilio M., Setten, Mariano G., Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Pozo, Norberto C., Grubissich, Nicolas, Plotnikow, Gustavo A., Vasquez, Daniela N., Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A., Saenz, María G., Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E., Cerrato, Valeria I., Bezzi, Marco G., Borello, Silvina A., Loiacono, Flavia A., Fernandez, Adriana M., Knowles, Serena, Reynolds, Claire, Inskip, Deborah M., Miller, Jennene J., Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J., Millar, Rebecca T., Mckenna, Toni E., Bailey, Irene M., Hanlon, Gabrielle C., Aneman, Anders, Lynch, Joan M., Azad, Raman, Neal, John, Woods, Paul W., Roberts, Brigit L., Kol, Mark R., Wong, Helen S., Riss, Katharina C., Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A., Dive, Alain M., Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I., Beraldo, Daniel O., Piras, Claudio, Rampinelli, Adenilton M., Nassar, Antonio P., Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M., Gonçalves, Claudio H., Antônio, Ana Carolina P., Ascoli, Aline, Biondi, Rodrigo S., Fontenele, Danielle C., Nobrega, Danielle, Sales, Vanessa M., Shindhe, Suresh, Ismail, Dk Maizatul Aiman B. Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G., Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C., Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D., Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R., Garcia, Patricio H., Aliaga, Felipe A., Farías, Pamela A., Yumha, Jacob S., Ortiz, Claudia A., Salas, Javier E., Saez, Alejandro A., Vega, Luis D., Labarca, Eduardo F., Martinez, Felipe T., Carreño, Nicolás G., Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L., Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya, Huang, Xiao B., He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X., Qin, Shu H., Zhu, Bao H., Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L., Zhou, Fa, Li, Qiong J., Zhang, Xing Y., Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N., Zhao, Xian Y., Li, Yuan Y., Li, Xiao L., Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q., Zhu, Wei H., Hang, Ai, Hua, Ma, Li, Yimin, Xu, Yonghao, Di, Yu, Ling, Long L., Qin, Tie H., Wang, Shou H., Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P., Jimenez, Juan I. Silesky, Rojas, Manuel A. González, Solis-Quesada, Jaime E., Ramirez-Alfaro, Christian M., Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G., Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H., Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L., Besset, Sebastien L., Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J., Phan, Nga T., Berkelmans, Frantz, Badie, Julio C., Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M., Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Zein, Salem Ould, Richecoeur, Jack R., Combaux, Daniele M., Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P., Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D., Meybohm, Patrick, Reske, Andreas W., Simon, Philipp, Hopf, Hans-Bernd F., Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N., Papavasilopoulou, Theonymfi G., Zacharas, Giannis A., Ourailogloy, Vasilis, Mouloudi, Eleni K., Massa, Eleni V., Nagy, Eva O., Stamou, Electra E., Kiourtzieva, Ellada V., Oikonomou, Marina A., Avila, Luis E., Cortez, Cesar A., Citalán, Johanna E., Jog, Sameer A., Sable, Safal D., Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K., Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J., Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B., Rhayakar, Rachana V., Ramakrishnan, Nagarajan, Bhardwaj, Vallish K., Mahto, Heera L., Sagar, Sudha V., Palaniswamy, Vijayanand, Ganesan, Deeban, Hashemian, Seyed Mohammadreza, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A., Nichol, Alistair, Knapman, Karl M., O’Croinin, Donall, Dunne, Eimhin S., Breen, Dorothy M., Clarkson, Kevin P., Jaafar, Rola F., Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O., O’Muircheartaigh, Aogan C., Black, Colin S., Treanor, Nuala, Collins, Daniel V., Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A., Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M., Montini, Luca M., Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R., Poli, Michela M., Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Pattarino, Pierpaolo Terragni Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E., Cracchiolo, Andrea N., Palma, Daniela M., Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R., Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A., Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N., Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y., Ñamendys-Silva, Silvio A., Jarquin-Badiola, Yves D., Sanchez-Hurtado, Luis A., Gomez-Flores, Saira S., Marin, Maria C., Villagomez, Asisclo J., Lemus, Jordana S., Fierro, Jonathan M., Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Dector, Dulce, Dector, Dulce M., Gonzalez, Daniel R., Estrella, Claudia R., Sanchez-Medina, Jorge R., Ramirez-Gutierrez, Alvaro, George, Fernando G., Aguirre, Janet S., Buensuseso, Juan A., Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M., Schouten, Jeroen A., Rinia, Myra, Raaijmakers, Monique, van Wezel, Hellen M., Heines, Serge J., Strauch, Ulrich, Buise, Marc P., Goodson, Jennifer C., Browne, Troy S., Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A., Bailey, Mathew B., Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J., Andersen, Finn H., Dolva, Merete S., Laake, Jon H., Barratt-Due, Andreas, Noremark, Kim Andre L., Søreide, Eldar, Sjøbø, Brit Å., Guttormsen, Anne B., Yoshido, Hector H. Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A. Montes, Alisasis, Alain U., Robles, Joanne B., Pasanting-Lim, Rossini Abbie B., Tan, Beatriz C., Andruszkiewicz, Pawel, Jakubowska, Karina, Coxo, Cristina M., Alvarez, António M., Oliveira, Bruno S., Montanha, Gustavo M., Barros, Nelson C., Pereira, Carlos S., Messias, António M., Monteiro, Jorge M., Araujo, Ana M., Catorze, Nuno T., Marum, Susan M., Bouw, Maria J., Gomes, Rui M., Brito, Vania A., Castro, Silvia, Estilita, Joana M., Barros, Filipa M., Serra, Isabel M., Martinho, Aurelia M., Tomescu, Dana R., Marcu, Alexandra, Bedreag, Ovidiu H., Papurica, Marius, Corneci, Dan E., Negoita, Silvius Loan, Grigoriev, Evgeny, Gritsan, Alexey I., Gazenkampf, Andrey A., Almekhlafi, Ghaleb, Albarrak, Mohamad M., Mustafa, Ghanem M., Maghrabi, Khalid A., Salahuddin, Nawal, Aisa, Tharwat M., Jabbary, Ahmed S. Al, Tabhan, Edgardo, Arabi, Yaseen M., Trinidad, Olivia A., Dorzi, Hasan M. Al, Tabhan, Edgardo E., Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C., Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, de Haro, Candelaria, Albaiceta, Guillermo M., de Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L., Claraco-Vega, Luis M., Soler, Juan Alfonso, Del Carmen Lorente, Maria, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B., Perez, Manuel P., Perez, Cesar P., Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C., de Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Ma Teresa, Arizmendi, Alfons, Piacentini, Enrique A., Franco, Nieves, Honrubia, Teresa, Cheng, Meisy Perez, Losada, Elena Perez, Blanco, Javier, Yuste, Luis J., Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G., Alonso, Javier G., Alda, Rosa S., Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Navalpotro, Miguel Angel Blasco, Abad, Ricardo Diaz, González, Raquel Montiel, Toribio, Dácil Parrilla, Castro, Alejandro G., Artiga, Maria Jose D., Penuelas, Oscar, Roser, Tomas P., Olga, Moreno F., Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P., Elisabet, Garcia M., Claverias, Laura, Magret, Monica, Pellicer, Ana M., Rodriguez, Lucia L., Sánchez-Ballesteros, Jesús, González-Salamanca, Ángela, Jimenez, Antonio G., Huerta, Francisco P., Diaz, Juan Carlos J. Sotillo, Lopez, Esther Bermejo, Moya, David D. Llinares, Alfonso, Alec A. Tallet, Luis, Palazon Sanchez Eugenio, Cesar, Palazon Sanchez, Rafael, Sánchez I., Virgilio, Corcoles G., Recio, Noelia N., Adamsson, Richard O., Rylander, Christian C., Holzgraefe, Bernhard, Broman, Lars M., Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lars, Helleberg, Johan, Eriksson, Karin E., Glietsch, Rita, Larsson, Niklas, Nygren, Ingela, Nunes, Silvia L., Morin, Anna-Karin, Kander, Thomas, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Souissi, Asma Ben, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O., Derman, Suleyman S., Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K., Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S., Fawkes, Danielle A., Watt, Philip, Twohey, Linda, Thomas, Rajeev R. Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J., Hormis, Anil P., Kannan, Santhana G., Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolcs, Nutt, Christopher, O’Neill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J., Ellis, Helen E., McKechnie, Stuart, Hutton, Paula J., Di Tomasso, Nora N., Vitale, Michela N., Griffin, Ruth O., Dean, Michael N., Cranshaw, Julius H., Willett, Emma L., Ioannou, Nicholas, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D., Williams, Alexandra J., Boyd, Owen, de Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K., Wenham, Tim, Szakmany, Tamas, Toth-Tarsoly, Piroska, McCalman, Katie H., Alexander, Peter, Stephenson, Lorraine, Collyer, Thomas, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M., Sim, Malcolm, Wrathall, David W., Irvine, Donald A., Zantua, Kim S., Adams, John C., Burtenshaw, Andrew J., Sellors, Gareth P., Welters, Ingeborg D., Williams, Karen E., Hessell, Robert J., Oldroyd, Matthew G., Battle, Ceri E., Pillai, Suresh, Kajtor, Istvan, Sivashanmugavel, Mageswaran, O’Kane, Sinead C., Donnelly, Adrian, Frigyik, Aniko D., Careless, Jon P., May, Martin M., Stewart, Richard, Trinder, T. John, Hagan, Samantha J., Wise, Matt P., Cole, Jade M., MacFie, Caroline C., Dowling, Anna T., Nin, Nicolás, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C., Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M., Beitler, Jeremy R., Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn, John O., Gomaa, Dina, Tainter, Christopher, Yeatts, Dale J., Warren, Jessica, Lanspa, Michael J., Miller, Russel R., Grissom, Colin K., Brown, Samuel M., Bauer, Philippe R., Gosselin, Ryan J., Kitch, Barrett T., Cohen, Jason E., Beegle, Scott H., Gueret, Renaud M., Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G., Lamb, Keith D., Oetting, Trevor W., Mohr, Nicholas M., Judy, Claine, Saito, Shigeki, Kheir, Fayez M., Kheir, Fayez, Schlichting, Adam B., Delsing, Angela, Crouch, Daniel R., Elmasri, Mary, Ismail, Dina, Dreyer, Kyle R., Blakeman, Thomas C., Baron, Rebecca M., Grijalba, Carolina Quintana, Hou, Peter C., Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L., Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, and Veljovic, Milic
Abstract: Purpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01–1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. Conclusions: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. Trial Registration: ClinicalTrials.gov NCT02010073
Published: 2018

28. Vitamin K: Nutrition, Metabolism and Current Evidence from Clinical Trials.

Author: Dahlberg, Sofia, Nilsson, Caroline, KANDER, THOMAS, Schött, Ulf, Dahlberg, Sofia, Nilsson, Caroline, KANDER, THOMAS, and Schött, Ulf
Published: 2018

29. Dose-response effects of omega-3 on platelet aggregation: an observational study

Author: KANDER, THOMAS, Lindblom, Erik, Schött, Ulf, KANDER, THOMAS, Lindblom, Erik, and Schött, Ulf
Abstract: ObjectiveThis study aimed to evaluate the dose-response effects of supplemental omega-3 fatty acids on platelet function in healthy volunteers.MethodsTwelve healthy volunteers ingested a normal supplemental dose of 1260 mg omega-3 fatty acids daily for 5 days, followed by a high dose of 2520 mg daily for another 5 days. Multiple electrode aggregometry (MEA) with four different agonists was used to measure platelet aggregation before and after the normal- and high-dose regimes. In vitro spiking using physiological doses of omega-3 fatty acids was also performed to determine whether MEA is capable of detecting a platelet-inhibiting effect due to omega-3 fatty acids.ResultsThere were no differences in platelet aggregation measured by the MEA assay in healthy volunteers after intake of either the normal or high dose of omega-3 fatty acids. In the in vitro experiment, a platelet-inhibiting effect of omega-3 fatty acids was shown by an arachidonic acid agonist in MEA .ConclusionsSupplemental omega-3 fatty acids do not evoke their positive health effects through inhibition of platelet aggregation measurable with MEA.
Published: 2018

30. Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study

Author: Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, Tynngård, Nahreen, Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, and Tynngård, Nahreen
Abstract: Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.
Published: 2016
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31. Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study

Author: Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, Tynngård, Nahreen, Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, and Tynngård, Nahreen
Abstract: Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.
Published: 2016
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32. Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study

Author: Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, Tynngård, Nahreen, Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, and Tynngård, Nahreen
Abstract: Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.
Published: 2016
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33. Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study

Author: Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, Tynngård, Nahreen, Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, and Tynngård, Nahreen
Abstract: Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.
Published: 2016
Full Text: View/download PDF

34. Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study

Author: Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, Tynngård, Nahreen, Kander, Thomas, Larsson, Anna, Taune, Victor, Schott, Ulf, and Tynngård, Nahreen
Abstract: Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.
Published: 2016
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35. Sepsis : vår tids okända folksjukdom

Author: Mellhammar, Lisa, Kander, Thomas, Christensson, Bertil, Herwald, Heiko, Egesten, Arne, Larsson, Anders, Sjölin, Jan, Brink, Magnus, Mehle, Christer, Hanberger, Håkan, Gårdlund, Bengt, Oldner, Anders, Källman, Jan, Linder, Adam, Mellhammar, Lisa, Kander, Thomas, Christensson, Bertil, Herwald, Heiko, Egesten, Arne, Larsson, Anders, Sjölin, Jan, Brink, Magnus, Mehle, Christer, Hanberger, Håkan, Gårdlund, Bengt, Oldner, Anders, Källman, Jan, and Linder, Adam
Published: 2015

36. Temperature effects on haemostasis in whole blood from ticagrelor- and aspirin-treated patients with acute coronary syndrome.

Author: Kander, Thomas, Brokopp, Jens, Erlinge, David, Lood, Christian, Schött, Ulf, Kander, Thomas, Brokopp, Jens, Erlinge, David, Lood, Christian, and Schött, Ulf
Abstract: Background. Comatose survivors after cardiac arrest are treated with mild induced hypothermia and potent platelet- inhibiting drugs after coronary stenting. Previous studies have shown an increased incidence of stent thrombosis during clopidogrel and aspirin treatment in conjunction with induced hypothermia. The aim of this study was to investigate the in vitro effect of induced hypo- and hyperthermia on blood from patients undergoing ticagrelor- and aspirin-mediated platelet inhibition. Methods. Whole blood from 15 patients with acute coronary syndrome who were treated with ticagrelor and aspirin and from eight healthy volunteers was incubated for 1 hour at 28, 33, 37, and 39°C. Results. In blood from patients with acute coronary syndrome, the activated clotting time (Sonoclot) was prolonged in mild hypothermic (33°C) compared to normothermic (37°C) samples. Sonoclot, clotting rate and platelet function were decreased in hypothermic compared to normothermic samples. Platelet-induced activation and aggregation (Multiplate(®)) was unchanged in mild hypothermic compared to normothermic samples. In contrast, mild hypothermia supported increased platelet activation as measured with flow cytometry with up-regulation of PAC-1 and P-selectin on the platelet surface. Conclusion. In acute coronary syndrome patients treated with ticagrelor and aspirin, in vitro hypothermia to 33°C markedly increased platelet activity measured with flow cytometry, whereas viscoelastic coagulation test (Sonoclot) revealed a hypocoagulative response. Prospective clinical trials studying platelet inhibition at different temperatures and correlating changes in platelet function to bleeding or stent occlusion are needed.
Published: 2015

37. Aspects of bleeding complications and hemostasis at central line insertion and mild induced hypothermia

Author: Kander, Thomas and Kander, Thomas
Abstract: Bleeding complications range from 0.5 to 1.6% in connection with central venous catheter insertions but are more frequent in patients with bone marrow failure and severe thrombocytopenia. Although supportive evidence is scarce, prophylactic platelet transfusion is sometimes performed in these patients before catheter insertion. Furthermore, the ideal threshold platelet count and timing of transfusion remain controversial among clinical studies. Hypothermia is generally considered to reduce coagulation and platelet function. However, studies performed in animals, healthy volunteers, and patients have shown conflicting results. Paper I, a retrospective study in non-intensive care unit patients, showed that serious bleeding complications in association with central line insertions were uncommon and that insertion of a large bore catheter may be an independent risk factor for mild bleeding complications in this population. Paper II, a prospective observational study, evaluated the efficacy of prophylactic platelet transfusions in thrombocytopenic patients with bone marrow failure. Transfusion improved hemostatic parameters in ROTEM and Multiplate tests by increasing the number of platelets and not by enhancing platelet function. Improved clotting parameters persisted between 1 and 4 hours after transfusion. Paper III demonstrated increased platelet aggregation and strengthened clot formation over time in out-of-hospital cardiac arrest patients treated with hypothermia. In patients with dual platelet inhibition, including ticagrelor and aspirin, this effect was offset by powerful P2Y12 blockade, confirmed by analysis of vasodilator-stimulated phosphoprotein. The effect of ticagrelor was delayed in survivors of cardiac arrest, probably due to slow gastric emptying. Paper IV demonstrated prolonged clot initiation and decreased clot propagation in ROTEM testing (EXTEM, FIBTEM, and APTEM assays) in whole blood from out-of-hospital cardiac arrest patients treated with mild in
Published: 2014

38. Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study

Author: Kander, Thomas, Dankiewicz, Josef, Friberg, Hans, Schött, Ulf, Kander, Thomas, Dankiewicz, Josef, Friberg, Hans, and Schött, Ulf
Abstract: Introduction: We conducted a prospective observational study in cardiac arrest survivors treated with mild induced hypothermia, evaluating different platelet function tests at hypo-and normothermia. We also investigated the relation between gastric emptying and vasodilator stimulated phosphoprotein (VASP). Methods: Comatose survivors of out of hospital cardiac arrest were included and divided into two groups, depending on whether dual platelet inhibition with peroral ticagrelor and aspirin was given or not. The first blood samples (T1) were collected 12-24 hours after reaching target temperature (33 degrees C) and were compared to blood samples collected 12-28 hours after reaching normothermia (37 degrees C) (T2) within each group. All samples were analysed by Sonoclot viscoelasticity, flow cytometry based VASP and with multiple electrode aggregometry, Multiplate (R); adenosine diphosphate (ADP), collagen (COL), thrombin receptor agonist peptide (TRAP) and arachidonic acid (ASPI). Sonoclot and Multiplate (R) instruments were set on in vivo temperatures. Gastric secretion from the nasogastric tube was measured to assess absorption of per orally administered antiplatelet drugs. Differences between T1 and T2 within each group were calculated using Wilcoxon matched pairs signed test. Significance levels were set at P < 0.01. Results: In total, 23 patients were included. In patients with dual platelet inhibition (n = 14) Multiplate (R)-analyses showed no changes in ADP stimulated platelets. COL, TRAP and ASPI aggregations were higher at T2 compared to T1. Sonoclot-analyses showed that activated clotting time (ACT) was unchanged but both clot rate (CR) and platelet function (PF) were higher at T2 compared to T1. VASP decreased from 53 +/- 28(T1) to 24 +/- 22(T2), (P < 0.001). The average volume of gastric secretion aspirated before T1 correlated well with VASP (T1), r = 0.81 (P < 0.001). In patients with no platelet inhibition, (n = 9) similar changes between T1 and T2 we
Published: 2014

39. 29-årig splenektomerad man avled av pneumokocksepsis. Viktigt att pneumokockvaccination av splenektomerade inte glöms bort.

Author: Werner, Simon, Winstedt, Dag, Kander, Thomas, Werner, Simon, Winstedt, Dag, and Kander, Thomas
Published: 2012

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