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1. Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

Author

Lucillia Bezu, Dilara Akçal Öksüz, Max Bell, Donal Buggy, Oscar Diaz-Cambronero, Mats Enlund, Patrice Forget, Anil Gupta, Markus W. Hollmann, Daniela Ionescu, Iva Kirac, Daqing Ma, Zhirajr Mokini, Tobias Piegeler, Giuseppe Pranzitelli, Laura Smith, and The EuroPeriscope Group

Subjects
anesthesia, cancer, immune factors, surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics’ impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.

Published
2024
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2. Effect of perioperative cognitive behavioural therapy on chronic post-surgical pain among breast cancer patients with high pain catastrophising characteristics: protocol for a double-blinded randomised controlled trial

Author

Aneurin Moorthy, Damien Lowry, Carla Edgley, Maire-Brid Casey, and Donal Buggy

Subjects
Breast cancer surgery, Chronic postsurgical pain, Mastectomy, Cognitive behavioural therapy, Psychological factors, Pain catastrophizing, Medicine (General), R5-920
Abstract

Abstract Background Surgery is regarded as the primary treatment for breast cancer. Chronic post-surgical pain (CPSP) is a recognised complication after breast cancer surgery, and it is estimated to affect 20–30% of women. Pain catastrophizing has emerged as one of the most influential psychological variables associated with CPSP. Methods This trial will be a single-centre, prospective, double-blinded, superiority, randomised controlled trial (RCT). Patients scheduled for elective breast cancer surgery (wide local excision or mastectomy with or without axillary lymph node dissection) will be screened preoperatively for high pain catastrophising. Patients with high pain catastrophising, defined as a score of ≥ 24 on the Pain Catastrophising Scale will be deemed eligible for inclusion in the study. Participants will be randomly assigned to receive either a cognitive behavioural therapy or an educational mindfulness based programme during their perioperative period. The primary outcome is the Brief Pain Inventory short form average pain severity score at 3 months postoperatively. Secondary outcomes include patient-reported quality of recovery at days 1–2 after surgery, levels of pain catastrophising, reported depressed mood and anxiety. Discussion To the best of our knowledge, this protocol describes the first RCT which directly examines the effect of perioperative cognitive behavioural therapy on CPSP among breast cancer patients with high pain catastrophising characteristics. The outcomes of this trial may have significant implications for these patients because perioperative cognitive behavioural therapy has the potential to become an important perioperative intervention to complement patient management. Trial registration ClinicalTrials.gov NCT04924010 . Registered on 11 June 2021. All item from the World Health Organisation Trial Registration Data set have been included.

Published
2022
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3. Ultrasound-guided erector spinae plane catheter versus video-assisted paravertebral catheter placement in minimally invasive thoracic surgery: comparing continuous infusion analgesic techniques on early quality of recovery, respiratory function and chronic persistent surgical pain: study protocol for a double-blinded randomised controlled trial

Author

Aneurin Moorthy, Aisling Ni Eochagain, Eamon Dempsey, and Donal Buggy

Subjects
Erector spinae catheter, Paravertebral catheter, Minimal invasive thoracic surgery, Quality of recovery, Chronic persistent surgical pain, Randomised controlled trial, Medicine (General), R5-920
Abstract

Abstract Background Compared to conventional thoracotomy, minimally invasive thoracic surgery (MITS) can reduce postoperative pain, reduce tissue trauma and contribute to better recovery. However, it still causes significant acute postoperative pain. Truncal regional anaesthesia techniques such as paravertebral and erector spinae blocks have shown to contribute to postoperative analgesia after MITS. Satisfactory placement of an ultrasound-guided thoracic paravertebral catheter can be technically challenging compared to an ultrasound-guided erector spinae catheter. However, in MITS, an opportunity arises for directly visualised placement of a paravertebral catheter by the surgeon under thoracoscopic guidance. Alongside with thoracic epidural, a paravertebral block is considered the “gold standard” of thoracic regional analgesic techniques. To the best of our knowledge, there are no randomised controlled trials comparing surgeon-administered paravertebral catheter and anaesthesiologist-assisted erector spinae catheter for MITS in terms of patient-centred outcomes such as quality of recovery. Methods This trial will be a prospective, double-blinded randomised controlled trial. A total of 80 eligible patients will be randomly assigned to receive either an anaesthesiologist-assisted ultrasound-guided erector spinae catheter or a surgeon-assisted video-assisted paravertebral catheter, in a 1:1 ratio following induction of general anaesthesia for minimally assisted thoracic surgery. Both groups will receive the same standardised analgesia protocol for both intra- and postoperative periods. The primary outcome is defined as Quality of Recovery (QoR-15) score between the two groups at 24 h postoperative. Secondary outcomes include assessment of chronic persistent surgical pain (CPSP) at 3 months postoperative using the Brief Pain Inventory (BPI) Short Form and Short Form McGill (SF-15) questionnaires, assessment of postoperative pulmonary function, area under the curve for Verbal Rating Score for pain at rest and on deep inspiration versus time over 48 h, total opioid consumption over 48 h, QoR-15 at 48 h, and postoperative complications and morbidity as measured by the Comprehensive Complication Index. Discussion Despite surgical advancements in thoracic surgery, severe acute postoperative pain following MITS is still prevailing. This study will provide recommendations about the efficacy of an anaesthesia-administered ultrasound-guided erector spinae catheter or surgeon-administered, video-assisted paravertebral catheter techniques for early quality of recovery following MITS. Trial registration ClinicalTrials.gov NCT04729712 . Registered on 28 January 2021. All items from the World Health Organization Trial Registration Data Set have been included.

Published
2021
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4. Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair – Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial

Author

Iain Keith Moppett, Stuart White, Richard Griffiths, and Donal Buggy

Subjects
Humans, Hypotension/complications, Hypotension/mortality, Monitoring, Intra-operative, Post-operative complications/aetiology, Medicine (General), R5-920
Abstract

Abstract Background Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. Methods/design We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. Discussion This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study. Trial registration ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.

Published
2017
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5. How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence

Author

Patrice Forget, Jose A. Aguirre, Ivanka Bencic, Alain Borgeat, Allessandro Cama, Claire Condron, Christina Eintrei, Pilar Eroles, Anil Gupta, Tim G. Hales, Daniela Ionescu, Mark Johnson, Pawel Kabata, Iva Kirac, Daqing Ma, Zhirajr Mokini, Jose Luis Guerrero Orriach, Michael Retsky, Sergio Sandrucci, Wiebke Siekmann, Ljilja Štefančić, Gina Votta-Vellis, Cara Connolly, and Donal Buggy

Subjects
cancer, anesthesia, analgesia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

Published
2019
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6. Preserving the endothelial glycocalyx in patients undergoing cardiopulmonary bypass: a prospective randomised interventional pilot study of lidocaine and doxycycline (LiDEG trial) [version 1; peer review: 3 approved with reservations, 1 not approved]

Author

Adrian Pannekoek, Mark Johnson, Donal Buggy, and Warren Pavey

Subjects
Study Protocol, Articles, Endothelial glycocalyx, lidocaine, doxycycline, cardiopulmonary bypass, anaesthesia
Abstract

Background: During major surgery, particularly heart surgery, an element of the lining of blood vessels, known as the endothelial glycocalyx (EG), can be damaged. This can lead to swelling, low oxygen levels, kidney failure and other problems, which delay recovery. There are laboratory studies that show lidocaine (a local anaesthetic) and doxycycline (an antibiotic) may help protect this lining. The study agents are widely available, cheap and safe drugs. Trial design and objective: This is a phase IV, single centre, prospective, unblinded, randomised, parallel-group trial. The objectives of the trial are to investigate the role of doxycycline and lidocaine as potential agents to reduce EG shedding and correlate with early postoperative outcomes. Methods: 60 adult patients undergoing heart surgery requiring cardiopulmonary bypass (CPB) will be randomly assigned to one of three groups: doxycycline group (oral doxycycline, 200mg preoperatively); lidocaine group (perioperative intravenous lidocaine, 1.5mg/kg bolus at induction followed by 2mg/kg/hr infusion for the duration of surgery); and control group (standard care). The randomisation will be undertaken using a sealed opaque envelope method. The primary outcome will be the relative difference in the biochemical marker of EG injury, syndecan-1, at different timepoints in the intraoperative and early post-operative period. Secondary endpoints include vasopressor requirements, markers of organ dysfunction (lung, kidney, brain, arrhythmia), coagulation and inflammation. Discussion: EG injury is ubiquitous in patients undergoing CPB. Maintaining homeostasis of this delicate layer would appear to be a valuable therapeutic target. To date no agents have been shown to be effective in protecting the EG. Our study agents have shown some promise in the preclinical setting and would represent a novel therapeutic approach should they show a protective effect. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12619000621112 (26 th April 2019).

Published
2020
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7. Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure

Author

Alexander I.R. Jackson, Oliver Boney, Rupert M. Pearse, Andrea Kurz, D. James Cooper, Wilton A. van Klei, Luca Cabrini, Timothy E. Miller, S. Ramani Moonesinghe, Paul S. Myles, Michael P.W. Grocott, Paul Myles, T.J. Gan, Phil Peyton, Dan Sessler, Martin Tramèr, Alan Cyna, Gildasio S. De Oliveira, Christopher Wu, Mark Jensen, Henrik Kehlet, Mari Botti, Guy Haller, Mike Grocott, Tim Cook, Lee Fleisher, Mark Neuman, David Story, Russell Gruen, Sam Bampoe, Lis Evered, David Scott, Brendan Silbert, Diederik van Dijk, Cor Kalkman, Matthew Chan, Hilary Grocott, Rod Eckenhoff, Lars Rasmussen, Lars Eriksson, Scott Beattie, Duminda Wijeysundera, Giovanni Landoni, Kate Leslie, Bruce Biccard, Simon Howell, Peter Nagele, Toby Richards, Andre Lamy, Manoj Lalu, Rupert Pearse, Monty Mythen, Jaume Canet, Ann Moller, Tony Gin, Marcus Schultz, Paolo Pelosi, Marcelo Gabreu, Emmanuel Futier, Ben Creagh-Brown, Tom Abbot, Andy Klein, Tomas Corcoran, D. Jamie Cooper, Stefan Dieleman, Elisabeth Diouf, David McIlroy, Rinaldo Bellomo, Andrew Shaw, John Prowle, Keyvan Karkouti, Josh Billings, David Mazer, Mohindas Jayarajah, Michael Murphy, Justyna Bartoszko, Rob Sneyd, Steve Morris, Ron George, Ramani Moonesinghe, Mark Shulman, Meghan Lane-Fall, Ulrica Nilsson, Nathalie Stevenson, Wilton van Klei, Tim Miller, Sandy Jackson, Donal Buggy, Tim Short, Bernhard Riedel, Vijay Gottumukkala, Nathan Pace, Bilal Alkhaffaf, Mark Johnson, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, and AII - Inflammatory diseases

Subjects
surgery, Anesthesiology and Pain Medicine, consensus, morbidity, organ failure, anaesthesia, postoperative morbidity, perioperative outcomes, mortality
Abstract

Background: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. Methods: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. Results: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien–Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien–Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. Conclusions: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien–Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Published
2023

8. The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence

Author

Masae Iwasaki, Hailin Zhao, Cong Hu, Junichi Saito, Lingzhi Wu, Aislinn Sherwin, Masashi Ishikawa, Atsuhiro Sakamoto, Donal Buggy, and Daqing Ma

Subjects
Health, Toxicology and Mutagenesis, Cell Biology, Toxicology
Abstract

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 μg g−1; ip injection) with or without 4 μg g−1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

Published
2022

9. Investigating the Influence of Anaesthesiology for Cancer Resection Surgery on Oncologic Outcomes: The Role of Experimental In Vivo Models

Author

Aneurin Moorthy, Ryan Howle, and Donal Buggy

Subjects
Analgesics, Anesthesiology, Neoplasms, Animals, Humans, Prospective Studies, General Medicine, Models, Theoretical, Anesthetics
Abstract

The incidence and societal burden of cancer is increasing globally. Surgery is indicated in the majority of solid tumours, and recent research in the emerging field of onco-anaesthesiology suggests that anaesthetic-analgesic interventions in the perioperative period could potentially influence long-term oncologic outcomes. While prospective, randomised controlled clinical trials are the only research method that can conclusively prove a causal relationship between anaesthetic technique and cancer recurrence, live animal (in vivo) experimental models may more realistically test the biological plausibility of these hypotheses and the mechanisms underpinning them, than limited in vitro modelling. This review outlines the advantages and limitations of available animal models of cancer and how they might be used in perioperative cancer metastasis modelling, including spontaneous or induced tumours, allograft, xenograft, and transgenic tumour models.

Published
2022

10. Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

Author

Grusser L., Keszei A., Coburn M., Rossaint R., Ziemann S., Kowark A, Daniela Filipescu, Sibylle Kozek-Langenecker, Juan V Llau Pitarch, Susan Mallett, Peter Martus, Idit Matot, Jens Meier, Axel Unterrainer, Dieter Adelmann, Daniel von Langen, Petra Innerhofer, Nicole Innerhofer-Pompernigg, Stefan De Hert, Luc De Baerdemaeker, Jurgen van Limmen, Piet Wyffels, Björn Heyse, Margot Vanderlaenen, Maud Beran, David Kahn, Audrey Prospiech, Luc Jamaer, Freya Mulders, Stefan Jacobs, Wannes Baeten, Sofie Platteau, Isabelle Maquoi, Severine Lauwick, Marc Senard, Vincent Ninane, Jean-Pierre Lecoq, Pierre Boveroux, Grégory Hans, Marcel Vercauteren, Brigitte Leva, Benoit Plichon, Vojislav Vujanovič, Ismet Suljevic, Hened Kelle, Denis Gustin, Matea Bogdanovic Dvorscak, Tamara Lupis, Jadranka Pavičić Šarić, Nataša Paklar, Dagmar Oberhofer, Ira Skok, Borana Kirigin, Ikic Visnja, Marina Kresic, Slavica Kvolik, Renatas Krobot, Vladimir Cerny, Jana Striteska, Marcela Bilska, Petr Štourač, Hana Harazim, Olga Smékalová, Martina Kosinová, Jozef Klučka, Rita Pacasová, Kim Ekelund, Indrek Rätsep, Juri Oganjan, Nadezda Smirnova, Peeter Kivik, Juri Karjagin, Alar Rokk, Alar Sõrmus, Bertrand Rozec, Jean-Christophe Rigal, Jean-Pierre Gouraud, Anne-Marie Chupin, Xavier Ambrosi, Laurent Brisard, Sylvie Decagny, Charles Marc Samama, Lionel Lidzborski, Matthieu Boisson, Anne-Laure Arcade, Gilbert Lorre, Peter Rosenberger, Hannah Merz, Ulrich Goebel, Bettina Schnitter, Hartmut Buerkle, Roland Tomasi, Vera von Dossow-Hanfstingl, Florian Brettner, Andreas Bayer, André Gottschalk, Nicolas Jakobs, Mark Coburn, Ana Kowark, Rolf Rossaint, Rita Laufenberg, Marion Ferner, Michael Schuster, Lydia Strys, Susanne Mauff, Kornel Skitek, Ewa Zielinska-Skitek, Gregor Schittek, Andreas Hoeft, Andreas Fleischer, Maria Wittmann, Florian Kessler, Anne Rohner, Peter Kranke, Christian Wunder, Johanna Jokinen, Kristin Budow, Christopher Prasser, Eva Werner, Alina Balandin, Norbert Ahrens, Kai Zacharowski, Patrick Meybohm, Kassiani Theodoraki, George Giokas, Tasoulis Marios-Konstantinos, Ageliki Pandazi, Aikaterini Kyttari, Eygenia Koursoumi, Georgios Anthopoulos, Antonis Andreou, Athanasios Rantis, Dimitrios Valsamidis, Pelagia Klimi, Konstantinos Katsanoulas, Demetrios Korfiotis, Christos Soumelidis, Fotios Papaspyros, Olga Kiskira, Tilemachos Paraskeuopoulos, Donal Buggy, Mortimer Kelleher, Liz Coghlan, Vladimir Verenkin, Anat Cattan, Francesco Bona, Felicino Debernardi, Andrea Cortegiani, Santi Maurizio Raineri, Giuseppe Accurso, Elena Gramigni, Leonardo Cenni, Laura Campiglia, Irene Lorenzi, Maria Grazia Militello, Tamara Biscioni, Andrius Macas, Daiva Apanaviciute, Darius Trepenaitis, Arunas Gelmanas, Diana Bilshiene, Jurate Sipylaite, Gabija Tomkute, Egle Kontrimaviciut, Renatas Tikuisis, Francis Borg, Ion Chesov, Serghei Cobiletchi, Victoria Moghildea, Bas Verdouw, J F van Poorten, Nick van Dasselaar, Marcus Daniel Lance, Britta de Waal, Lucienne Kropman, Peter van Noord, Benedikt Preckel, Lena Koers, Markus W Hollmann, Holger Baumann, Ankie W M M Koopman-van Gemert, Tore Reikvam, Tore Hervig, Kasper Gymoese Berthelsen, Ingvild Hausberg Sørvoll, Mirosław Czuczwar, Michał Borys, Paweł Piwowarczyk, Suzana Parente, Diogo Martins, Gloria Tareco, Ligia Reis, Joana Amaral, Daniel Ferreira, José Manuel Gonçalves Aguiar, Zélia Moreira, Filipa Lagarto, Filipa Pereira, Maria Lina Miranda, Sofia Serra, Alexandre Carrilho, José Pinto, Sandra Dias, Rita Poeria, Filipe Linda, Silvia Pica, Helder Martinho, Francisco Matias, Claudia Alves, Valentina Almeida, Margarida Marques, Emilia Martires, Piedade Gomes, Elizabete Pereira, Joana Jesus, Claudia Carreira, Carlos Seco, Carlos Bento, Helena Vieira, Luciane Pereira, Fernando Pinto, Luisa Silva, Marta Azenha, Maged Zarif, Ana Bernardino, Ana Raimundo, Ana Lopes, Melissa Fernandes, Beatriz Campos, Ana Macedo, Filipe Pinheiro, Sonia Duarte, Alexandra Saraiva, Catia Real, Marilena Alina Paunescu, Alexandru Bogdan Prodan, Mihai Stefan, Cristian Boros, Marius Tifrea, Anca Dragan, Horhota Lucian, Alida Moise, Carmen Arion-Balescu, Natalia Mincu, Viorel Gherghina, Iulia Cindea, Dan Costea, Ravzan Popescu, Dana Tomescu, Ecaterina Scarlatescu, Esenia Calancea, Ruxandra Copotoiu, Sanda Maria Copotoiu, Victoria Barsan, Dan Corneci, Rely Manolescu, Toma Diana, Denisa Nitu, Georgian Popica, Gabriela Droc, Nicoleta Jipa Lavina, Roxana Ciobanasu, Anna Maria Munteanu, Denisa Anastase, Iona Grintescu, Liliana Mirea, Alexandra Manoleli, Ciobanu Elena, Mary Nicoleta Lupu, Madalina Nina Sandu, Bicolae Bacalbasa, Florenta Calarasu, Alexey Grytsan, Andrey Gasenkampf, Alexander Kulikov, Alexander Shmigelsky, Vojislava Nescovic, Rade Vukovic, Uros Petrovic, Milic Veljovic, Dragana Unic-Stojanovic, Gordana Jovanovic, Ivana Kvrgic, Dragana Rakic, Roman Záhorec, Daniel Cintula, Tomas Veselovsky, Katarina Galkova, Jordana Stevikova, Andrea Číková, Zora Flassikova, Anna Dobisova, Jasmina Markovic Bozic, Minca Voje, Andriy Grynyuk, Alenka Spindler Yesel, Sabina Stivan, Peter Poredos, Darja Kasnik, Jasna Uranjek, Raquel Ferrandis, Sofia Machado, Liliana Henao, Tania Moreno, Ana Izquierdo, Carlos Delgado, Angela Camps, Susana Manrique, Alejandro Arbelaez, Pilar Tormos, Helena Serrano, Irene Garcia, Elvira Bisbe Vives, Luís Moltó, Tania Villar, Enrique Moret, Raquel Tolós, Esther Martínez, Misericordia Basora, Beatriz Tena, Roger Pujol, Jorge Vera Bella, Thomas Mallor, Pablo Mondero, Luis Lopez, Francisco Hidalgo, Maria Bermudez Lopez, Ana Velasco, Begona Bascuas, Victoria Moral, Diana Gómez Martinez, Alfredo Merten, J A Fernández, Nadia Diana Kinast, A Font, Maggi Genaro, Emilia Guasch, Fernando Gilsanz, Raul Martinez, Renato Schiraldi, Ever Martinez, Marta Barquero López, Alexo Lopez Alvarez, Yvan Enrique Sanchez Sanchez, Adriana Roman Fernandez, Olalla Varela Garcia, Marian Angeles Orallo Moran, Veronica Gonzalez Monzon, Óscar Sánchez López, David Sanchez Perez, Pablo Molano Diaz, Concepcion Cassinello, Maria Pilar Jubera, Maria Soler Pedrola, Julio Belmonte Cuenca, Sören Söndergaard, Till Rudolph, Kristin Åkeröy, Monir Jawad, Yousif Saeed, Sergej Safonov, Mona Andersson, Jan Wernerman, Suzanne Odeberg-Wernerman, Tommi Blom, Nesil Deger Coskunfirat, Zekiye Bigat, Suat Sanlı, O Koray Coskunfirat, Atilla Ramazanoğlu, Neval Boztug Uz, Ali Emre Camci, Omur Aksoy, Esra Saka, Oguzhan Arun, Sevda Ozkardesler, Dilek Omur, Mert Akan, Zuleyha Kazak Bengisun, Hakan Yılmaz, Perihan Ekmekci, Onur Selvi, Neslihan Alkis, Çiğdem Yıldırım, Başak Ceyda Meço, Zekeriyye Alanoğlu, Sergiy Vorotyntsev, Yevgen Yakymenko, Galina Troyan, Mohammed Alousi, Sarah James, Paula Meale, Ahmed Chishti, Matt Garner, Rita Singh, Nicola Hirschauer, Charley Higham, Andrea Bell, Alistair Cain, Chris Perry, Katy Davies, Claire Leech, Verity Calder, Shaman Jhanji, Varma Sandeep, Karen Simeson, Philip Watt, Nigel Dunk, Rosemary Ferrie, Margaret Wright, Lynn Everett, Andrew Ferguson, Laura Espie, Gail Browne, Matthew Dickinson, Ashok Nair, Deborah Clements, Peter Carvalho, Thomas Collyer, Jens Bolten, Lajos Zsisku, Attila Petri, Mohammed Ramadan, Tracey Ellimah, Martus, Peter, Laufenberg, Rita, Ferner, Marion, Schuster, Michael, Strys, Lydia, Mauff, Susanne, Skitek, Kornel, Zielinska-Skitek, Ewa, Schittek, Gregor, Hoeft, Andreas, Fleischer, Andreas, Matot, Idit, Wittmann, Maria, Kessler, Florian, Rohner, Anne, Kranke, Peter, Wunder, Christian, Jokinen, Johanna, Budow, Kristin, Prasser, Christopher, Werner, Eva, Balandin, Alina, Meier, Jens, Ahrens, Norbert, Zacharowski, Kai, Meybohm, Patrick, Theodoraki, Kassiani, Giokas, George, Marios-Konstantinos, Tasoulis, Pandazi, Ageliki, Kyttari, Aikaterini, Koursoumi, Eygenia, Anthopoulos, Georgios, Unterrainer, Axel, Andreou, Antonis, Rantis, Athanasios, Valsamidis, Dimitrios, Klimi, Pelagia, Katsanoulas, Konstantinos, Korfiotis, Demetrios, Soumelidis, Christos, Papaspyros, Fotios, Kiskira, Olga, Paraskeuopoulos, Tilemachos, Adelmann, Dieter, Buggy, Donal, Kelleher, Mortimer, Coghlan, Liz, Verenkin, Vladimir, Cattan, Anat, Bona, Francesco, Debernardi, Felicino, Cortegiani, Andrea, Raineri, Santi Maurizio, Accurso, Giuseppe, von Langen, Daniel, Gramigni, Elena, Cenni, Leonardo, Campiglia, Laura, Lorenzi, Irene, Militello, Maria Grazia, Biscioni, Tamara, Macas, Andrius, Apanaviciute, Daiva, Trepenaitis, Darius, Gelmanas, Arunas, Innerhofer, Petra, Bilshiene, Diana, Sipylaite, Jurate, Tomkute, Gabija, Kontrimaviciut, Egle, Tikuisis, Renatas, Borg, Francis, Chesov, Ion, Cobiletchi, Serghei, Moghildea, Victoria, Verdouw, Bas, Innerhofer-Pompernigg, Nicole, van Poorten, J. F., van Dasselaar, Nick, Lance, Marcus Daniel, de Waal, Britta, Kropman, Lucienne, van Noord, Peter, Preckel, Benedikt, Koers, Lena, Hollmann, Markus W., Baumann, Holger, De Hert, Stefan, Koopman-van Gemert, Ankie W. M. M., Reikvam, Tore, Hervig, Tore, Berthelsen, Kasper Gymoese, Sørvoll, Ingvild Hausberg, Czuczwar, Mirosław, Borys, Michał, Piwowarczyk, Paweł, Parente, Suzana, Martins, Diogo, De Baerdemaeker, Luc, Tareco, Gloria, Reis, Ligia, Amaral, Joana, Ferreira, Daniel, Gonçalves Aguiar, José Manuel, Moreira, Zélia, Lagarto, Filipa, Pereira, Filipa, Miranda, Maria Lina, Serra, Sofia, van Limmen, Jurgen, Carrilho, Alexandre, Pinto, José, Dias, Sandra, Poeria, Rita, Linda, Filipe, Pica, Silvia, Martinho, Helder, Matias, Francisco, Alves, Claudia, Almeida, Valentina, Wyffels, Piet, Marques, Margarida, Martires, Emilia, Gomes, Piedade, Pereira, Elizabete, Jesus, Joana, Carreira, Claudia, Seco, Carlos, Bento, Carlos, Vieira, Helena, Pereira, Luciane, Heyse, Björn, Pinto, Fernando, Silva, Luisa, Azenha, Marta, Zarif, Maged, Bernardino, Ana, Raimundo, Ana, Lopes, Ana, Fernandes, Melissa, Campos, Beatriz, Macedo, Ana, Vanderlaenen, Margot, Pinheiro, Filipe, Duarte, Sonia, Saraiva, Alexandra, Real, Catia, Paunescu, Marilena Alina, Bogdan Prodan, Alexandru, Stefan, Mihai, Boros, Cristian, Tifrea, Marius, Dragan, Anca, Beran, Maud, Lucian, Horhota, Moise, Alida, Arion-Balescu, Carmen, Mincu, Natalia, Gherghina, Viorel, Cindea, Iulia, Costea, Dan, Popescu, Ravzan, Tomescu, Dana, Scarlatescu, Ecaterina, Kahn, David, Calancea, Esenia, Copotoiu, Ruxandra, Copotoiu, Sanda Maria, Barsan, Victoria, Corneci, Dan, Manolescu, Rely, Diana, Toma, Nitu, Denisa, Popica, Georgian, Droc, Gabriela, Prospiech, Audrey, Jipa Lavina, Nicoleta, Ciobanasu, Roxana, Munteanu, Anna Maria, Anastase, Denisa, Grintescu, Iona, Mirea, Liliana, Manoleli, Alexandra, Elena, Ciobanu, Lupu, Mary Nicoleta, Sandu, Madalina Nina, Jamaer, Luc, Bacalbasa, Bicolae, Calarasu, Florenta, Grytsan, Alexey, Gasenkampf, Andrey, Kulikov, Alexander, Shmigelsky, Alexander, Nescovic, Vojislava, Vukovic, Rade, Petrovic, Uros, Veljovic, Milic, Mulders, Freya, Unic-Stojanovic, Dragana, Jovanovic, Gordana, Kvrgic, Ivana, Rakic, Dragana, Záhorec, Roman, Cintula, Daniel, Veselovsky, Tomas, Galkova, Katarina, Stevikova, Jordana, Číková, Andrea, Jacobs, Stefan, Flassikova, Zora, Dobisova, Anna, Markovic Bozic, Jasmina, Voje, Minca, Grynyuk, Andriy, Spindler Yesel, Alenka, Stivan, Sabina, Poredos, Peter, Kasnik, Darja, Uranjek, Jasna, Baeten, Wannes, Ferrandis, Raquel, Machado, Sofia, Henao, Liliana, Moreno, Tania, Izquierdo, Ana, Delgado, Carlos, Camps, Angela, Manrique, Susana, Arbelaez, Alejandro, Tormos, Pilar, Platteau, Sofie, Serrano, Helena, Garcia, Irene, Bisbe Vives, Elvira, Moltó, Luís, Villar, Tania, Moret, Enrique, Tolós, Raquel, Martínez, Esther, Basora, Misericordia, Tena, Beatriz, Maquoi, Isabelle, Pujol, Roger, Vera Bella, Jorge, Mallor, Thomas, Mondero, Pablo, Lopez, Luis, Hidalgo, Francisco, Bermudez Lopez, Maria, Velasco, Ana, Bascuas, Begona, Moral, Victoria, Lauwick, Severine, Gómez Martinez, Diana, Merten, Alfredo, Fernández, J. A., Kinast, Nadia Diana, Font, A., Genaro, Maggi, Guasch, Emilia, Gilsanz, Fernando, Martinez, Raul, Schiraldi, Renato, Senard, Marc, Martinez, Ever, Barquero López, Marta, Lopez Alvarez, Alexo, Sanchez Sanchez, Yvan Enrique, Roman Fernandez, Adriana, Varela Garcia, Olalla, Orallo Moran, Marian Angeles, Gonzalez Monzon, Veronica, Sánchez López, Óscar, Sanchez Perez, David, Ninane, Vincent, Molano Diaz, Pablo, Cassinello, Concepcion, Pilar Jubera, Maria, Soler Pedrola, Maria, Belmonte Cuenca, Julio, Söndergaard, Sören, Rudolph, Till, Åkeröy, Kristin, Jawad, Monir, Saeed, Yousif, Lecoq, Jean-Pierre, Safonov, Sergej, Andersson, Mona, Wernerman, Jan, Odeberg-Wernerman, Suzanne, Blom, Tommi, Deger Coskunfirat, Nesil, Bigat, Zekiye, Sanlı, Suat, Coskunfirat, O. Koray, Ramazanoğlu, Atilla, Boveroux, Pierre, Boztug Uz, Neval, Camci, Ali Emre, Aksoy, Omur, Saka, Esra, Arun, Oguzhan, Ozkardesler, Sevda, Omur, Dilek, Akan, Mert, Bengisun, Zuleyha Kazak, Yılmaz, Hakan, Hans, Grégory, Ekmekci, Perihan, Selvi, Onur, Alkis, Neslihan, Yıldırım, Çiğdem, Ceyda Meço, Başak, Alanoğlu, Zekeriyye, Vorotyntsev, Sergiy, Yakymenko, Yevgen, Troyan, Galina, Alousi, Mohammed, Vercauteren, Marcel, James, Sarah, Meale, Paula, Chishti, Ahmed, Garner, Matt, Singh, Rita, Hirschauer, Nicola, Higham, Charley, Bell, Andrea, Cain, Alistair, Perry, Chris, Leva, Brigitte, Davies, Katy, Leech, Claire, Calder, Verity, Jhanji, Shaman, Sandeep, Varma, Simeson, Karen, Watt, Philip, Dunk, Nigel, Ferrie, Rosemary, Wright, Margaret, Plichon, Benoit, Everett, Lynn, Ferguson, Andrew, Espie, Laura, Browne, Gail, Dickinson, Matthew, Nair, Ashok, Clements, Deborah, Carvalho, Peter, Collyer, Thomas, Bolten, Jens, Vujanovič, Vojislav, Zsisku, Lajos, Petri, Attila, Ramadan, Mohammed, Ellimah, Tracey, Suljevic, Ismet, Kelle, Hened, Gustin, Denis, Bogdanovic Dvorscak, Matea, Lupis, Tamara, Pavičić Šarić, Jadranka, Paklar, Nataša, Oberhofer, Dagmar, Skok, Ira, Kirigin, Borana, Visnja, Ikic, Kresic, Marina, Kvolik, Slavica, Krobot, Renatas, Cerny, Vladimir, Striteska, Jana, Bilska, Marcela, Filipescu, Daniela, Štourač, Petr, Harazim, Hana, Smékalová, Olga, Kosinová, Martina, Klučka, Jozef, Pacasová, Rita, Ekelund, Kim, Rätsep, Indrek, Oganjan, Juri, Smirnova, Nadezda, Kozek-Langenecker, Sibylle, Kivik, Peeter, Karjagin, Juri, Rokk, Alar, Sõrmus, Alar, Rozec, Bertrand, Rigal, Jean-Christophe, Gouraud, Jean-Pierre, Chupin, Anne-Marie, Ambrosi, Xavier, Brisard, Laurent, Llau Pitarch, Juan V., Decagny, Sylvie, Samama, Charles Marc, Lidzborski, Lionel, Boisson, Matthieu, Arcade, Anne-Laure, Lorre, Gilbert, Rosenberger, Peter, Merz, Hannah, Goebel, Ulrich, Schnitter, Bettina, Mallett, Susan, Buerkle, Hartmut, Tomasi, Roland, von Dossow-Hanfstingl, Vera, Brettner, Florian, Bayer, Andreas, Gottschalk, André, Jakobs, Nicolas, Coburn, Mark, Kowark, Ana, Rossaint, Rolf, Grusser L., Keszei A., Coburn M., Rossaint R., Ziemann S., Kowark A, Daniela Filipescu, Sibylle Kozek-Langenecker, Juan V Llau Pitarch, Susan Mallett, Peter Martus, Idit Matot, Jens Meier, Axel Unterrainer, Dieter Adelmann, Daniel von Langen, Petra Innerhofer, Nicole Innerhofer-Pompernigg, Stefan De Hert, Luc De Baerdemaeker, Jurgen van Limmen, Piet Wyffels, Björn Heyse, Margot Vanderlaenen, Maud Beran, David Kahn, Audrey Prospiech, Luc Jamaer, Freya Mulders, Stefan Jacobs, Wannes Baeten, Sofie Platteau, Isabelle Maquoi, Severine Lauwick, Marc Senard, Vincent Ninane, Jean-Pierre Lecoq, Pierre Boveroux, Grégory Hans, Marcel Vercauteren, Brigitte Leva, Benoit Plichon, Vojislav Vujanovič, Ismet Suljevic, Hened Kelle, Denis Gustin, Matea Bogdanovic Dvorscak, Tamara Lupis, Jadranka Pavičić Šarić, Nataša Paklar, Dagmar Oberhofer, Ira Skok, Borana Kirigin, Ikic Visnja, Marina Kresic, Slavica Kvolik, Renatas Krobot, Vladimir Cerny, Jana Striteska, Marcela Bilska, Petr Štourač, Hana Harazim, Olga Smékalová, Martina Kosinová, Jozef Klučka, Rita Pacasová, Kim Ekelund, Indrek Rätsep, Juri Oganjan, Nadezda Smirnova, Peeter Kivik, Juri Karjagin, Alar Rokk, Alar Sõrmus, Bertrand Rozec, Jean-Christophe Rigal, Jean-Pierre Gouraud, Anne-Marie Chupin, Xavier Ambrosi, Laurent Brisard, Sylvie Decagny, Charles Marc Samama, Lionel Lidzborski, Matthieu Boisson, Anne-Laure Arcade, Gilbert Lorre, Peter Rosenberger, Hannah Merz, Ulrich Goebel, Bettina Schnitter, Hartmut Buerkle, Roland Tomasi, Vera von Dossow-Hanfstingl, Florian Brettner, Andreas Bayer, André Gottschalk, Nicolas Jakobs, Mark Coburn, Ana Kowark, Rolf Rossaint, Rita Laufenberg, Marion Ferner, Michael Schuster, Lydia Strys, Susanne Mauff, Kornel Skitek, Ewa Zielinska-Skitek, Gregor Schittek, Andreas Hoeft, Andreas Fleischer, Maria Wittmann, Florian Kessler, Anne Rohner, Peter Kranke, Christian Wunder, Johanna Jokinen, Kristin Budow, Christopher Prasser, Eva Werner, Alina Balandin, Norbert Ahrens, Kai Zacharowski, Patrick Meybohm, Kassiani Theodoraki, George Giokas, Tasoulis Marios-Konstantinos, Ageliki Pandazi, Aikaterini Kyttari, Eygenia Koursoumi, Georgios Anthopoulos, Antonis Andreou, Athanasios Rantis, Dimitrios Valsamidis, Pelagia Klimi, Konstantinos Katsanoulas, Demetrios Korfiotis, Christos Soumelidis, Fotios Papaspyros, Olga Kiskira, Tilemachos Paraskeuopoulos, Donal Buggy, Mortimer Kelleher, Liz Coghlan, Vladimir Verenkin, Anat Cattan, Francesco Bona, Felicino Debernardi, Andrea Cortegiani, Santi Maurizio Raineri, Giuseppe Accurso, Elena Gramigni, Leonardo Cenni, Laura Campiglia, Irene Lorenzi, Maria Grazia Militello, Tamara Biscioni, Andrius Macas, Daiva Apanaviciute, Darius Trepenaitis, Arunas Gelmanas, Diana Bilshiene, Jurate Sipylaite, Gabija Tomkute, Egle Kontrimaviciut, Renatas Tikuisis, Francis Borg, Ion Chesov, Serghei Cobiletchi, Victoria Moghildea, Bas Verdouw, J F van Poorten, Nick van Dasselaar, Marcus Daniel Lance, Britta de Waal, Lucienne Kropman, Peter van Noord, Benedikt Preckel, Lena Koers, Markus W Hollmann, Holger Baumann, Ankie W M M Koopman-van Gemert, Tore Reikvam, Tore Hervig, Kasper Gymoese Berthelsen, Ingvild Hausberg Sørvoll, Mirosław Czuczwar, Michał Borys, Paweł Piwowarczyk, Suzana Parente, Diogo Martins, Gloria Tareco, Ligia Reis, Joana Amaral, Daniel Ferreira, José Manuel Gonçalves Aguiar, Zélia Moreira, Filipa Lagarto, Filipa Pereira, Maria Lina Miranda, Sofia Serra, Alexandre Carrilho, José Pinto, Sandra Dias, Rita Poeria, Filipe Linda, Silvia Pica, Helder Martinho, Francisco Matias, Claudia Alves, Valentina Almeida, Margarida Marques, Emilia Martires, Piedade Gomes, Elizabete Pereira, Joana Jesus, Claudia Carreira, Carlos Seco, Carlos Bento, Helena Vieira, Luciane Pereira, Fernando Pinto, Luisa Silva, Marta Azenha, Maged Zarif, Ana Bernardino, Ana Raimundo, Ana Lopes, Melissa Fernandes, Beatriz Campos, Ana Macedo, Filipe Pinheiro, Sonia Duarte, Alexandra Saraiva, Catia Real, Marilena Alina Paunescu, Alexandru Bogdan Prodan, Mihai Stefan, Cristian Boros, Marius Tifrea, Anca Dragan, Horhota Lucian, Alida Moise, Carmen Arion-Balescu, Natalia Mincu, Viorel Gherghina, Iulia Cindea, Dan Costea, Ravzan Popescu, Dana Tomescu, Ecaterina Scarlatescu, Esenia Calancea, Ruxandra Copotoiu, Sanda Maria Copotoiu, Victoria Barsan, Dan Corneci, Rely Manolescu, Toma Diana, Denisa Nitu, Georgian Popica, Gabriela Droc, Nicoleta Jipa Lavina, Roxana Ciobanasu, Anna Maria Munteanu, Denisa Anastase, Iona Grintescu, Liliana Mirea, Alexandra Manoleli, Ciobanu Elena, Mary Nicoleta Lupu, Madalina Nina Sandu, Bicolae Bacalbasa, Florenta Calarasu, Alexey Grytsan, Andrey Gasenkampf, Alexander Kulikov, Alexander Shmigelsky, Vojislava Nescovic, Rade Vukovic, Uros Petrovic, Milic Veljovic, Dragana Unic-Stojanovic, Gordana Jovanovic, Ivana Kvrgic, Dragana Rakic, Roman Záhorec, Daniel Cintula, Tomas Veselovsky, Katarina Galkova, Jordana Stevikova, Andrea Číková, Zora Flassikova, Anna Dobisova, Jasmina Markovic Bozic, Minca Voje, Andriy Grynyuk, Alenka Spindler Yesel, Sabina Stivan, Peter Poredos, Darja Kasnik, Jasna Uranjek, Raquel Ferrandis, Sofia Machado, Liliana Henao, Tania Moreno, Ana Izquierdo, Carlos Delgado, Angela Camps, Susana Manrique, Alejandro Arbelaez, Pilar Tormos, Helena Serrano, Irene Garcia, Elvira Bisbe Vives, Luís Moltó, Tania Villar, Enrique Moret, Raquel Tolós, Esther Martínez, Misericordia Basora, Beatriz Tena, Roger Pujol, Jorge Vera Bella, Thomas Mallor, Pablo Mondero, Luis Lopez, Francisco Hidalgo, Maria Bermudez Lopez, Ana Velasco, Begona Bascuas, Victoria Moral, Diana Gómez Martinez, Alfredo Merten, J A Fernández, Nadia Diana Kinast, A Font, Maggi Genaro, Emilia Guasch, Fernando Gilsanz, Raul Martinez, Renato Schiraldi, Ever Martinez, Marta Barquero López, Alexo Lopez Alvarez, Yvan Enrique Sanchez Sanchez, Adriana Roman Fernandez, Olalla Varela Garcia, Marian Angeles Orallo Moran, Veronica Gonzalez Monzon, Óscar Sánchez López, David Sanchez Perez, Pablo Molano Diaz, Concepcion Cassinello, Maria Pilar Jubera, Maria Soler Pedrola, Julio Belmonte Cuenca, Sören Söndergaard, Till Rudolph, Kristin Åkeröy, Monir Jawad, Yousif Saeed, Sergej Safonov, Mona Andersson, Jan Wernerman, Suzanne Odeberg-Wernerman, Tommi Blom, Nesil Deger Coskunfirat, Zekiye Bigat, Suat Sanlı, O Koray Coskunfirat, Atilla Ramazanoğlu, Neval Boztug Uz, Ali Emre Camci, Omur Aksoy, Esra Saka, Oguzhan Arun, Sevda Ozkardesler, Dilek Omur, Mert Akan, Zuleyha Kazak Bengisun, Hakan Yılmaz, Perihan Ekmekci, Onur Selvi, Neslihan Alkis, Çiğdem Yıldırım, Başak Ceyda Meço, Zekeriyye Alanoğlu, Sergiy Vorotyntsev, Yevgen Yakymenko, Galina Troyan, Mohammed Alousi, Sarah James, Paula Meale, Ahmed Chishti, Matt Garner, Rita Singh, Nicola Hirschauer, Charley Higham, Andrea Bell, Alistair Cain, Chris Perry, Katy Davies, Claire Leech, Verity Calder, Shaman Jhanji, Varma Sandeep, Karen Simeson, Philip Watt, Nigel Dunk, Rosemary Ferrie, Margaret Wright, Lynn Everett, Andrew Ferguson, Laura Espie, Gail Browne, Matthew Dickinson, Ashok Nair, Deborah Clements, Peter Carvalho, Thomas Collyer, Jens Bolten, Lajos Zsisku, Attila Petri, Mohammed Ramadan, Tracey Ellimah, Anesthesiology, ACS - Diabetes & metabolism, APH - Quality of Care, ACS - Heart failure & arrhythmias, APH - Global Health, and ACS - Microcirculation

Subjects
Clinical Oncology, Male, Science, Clinical Decision-Making, Cancer Treatment, Surgical and Invasive Medical Procedures, Geographical Locations, Diagnostic Medicine, Outcome Assessment, Health Care, Medicine and Health Sciences, Humans, Blood Transfusion, Prospective Studies, Aged, Aged, 80 and over, Intraoperative Care, Multidisciplinary, Transfusion Medicine, Anemia, Hematology, Clinical Laboratory Sciences, Health Care, Europe, Surgical Oncology, Oncology, Age Groups, Elective Surgical Procedures, People and Places, Medicine, Population Groupings, Female, Geriatric Care, Clinical Medicine, Erythrocyte Transfusion, Research Article
Abstract

PLOS ONE 17(1), e0262110 (2022). doi:10.1371/journal.pone.0262110, Published by PLOS, San Francisco, California, US

Published
2022

11. Systematic review and consensus definitions for the Standardized Endpoints in Perioperative Medicine (StEP) initiative: cardiovascular outcomes

Author

W. Scott Beattie, Manoj Lalu, Matthew Bocock, Simon Feng, Duminda N. Wijeysundera, Peter Nagele, Lee A. Fleisher, Andrea Kurz, Bruce Biccard, Kate Leslie, Simon Howell, Giovanni Landoni, Hilary Grocott, Andre Lamy, Toby Richards, Paul Myles, T.J. Gan, Phil Peyton, Dan Sessler, Martin Tramèr, Alan Cyna, Gildasio S. De Oliveira, Christopher Wu, Mark Jensen, Henrik Kehlet, Mari Botti, Oliver Boney, Guy Haller, Mike Grocott, Tim Cook, Lee Fleisher, Mark Neuman, David Story, Russell Gruen, Sam Bampoe, Lis Evered, David Scott, Brendan Silbert, Diederik van Dijk, Cor Kalkman, Matthew Chan, Rod Eckenhoff, Lars Rasmussen, Lars Eriksson, Scott Beattie, Duminda Wijeysundera, Richard J. Bartlett, Robert McMonnies, Jacob Gerstl, Mohammad Jay, David Kishlyansky, Matthew Machina, Matthew Bobcock, Rupert Pearse, Monty Mythen, Jaume Canet, Ann Moller, Tony Gin, Marcus Schultz, Paolo Pelosi, Marcelo Gabreu, Emmanuel Futier, Ben Creagh-Brown, Tom Abbott, Andy Klein, Tomas Corcoran, D. Jamie Cooper, Stefan Dieleman, Elisabeth Diouf, David McIlroy, Rinaldo Bellomo, Andrew Shaw, John Prowle, Keyvan Karkouti, Josh Billings, David Mazer, Mohindas Jayarajah, Michael Murphy, Justyna Bartoszko, Rob Sneyd, Steve Morris, Ron George, Ramani Moonesinghe, Mark Shulman, Meghan Lane-Fall, Ulrica Nilsson, Nathalie Stevenson, Jamie (DJ) Cooper, Wilton van Klei, Luca Cabrini, Tim Miller, Nathan Pace, Sandy Jackson, Donal Buggy, Tim Short, Bernhard Riedel, Vijay Gottumukkala, Bilal Alkhaffaf, Mark Johnson, Beattie, W. S., Lalu, M., Bocock, M., Feng, S., Wijeysundera, D. N., Nagele, P., Fleisher, L. A., Kurz, A., Biccard, B., Leslie, K., Howell, S., Landoni, G., Grocott, H., Lamy, A., Richards, T., Myles, P., Cooper, D. J., Gan, T. J., Peyton, P., Sessler, D., Tramer, M., Cyna, A., De Oliveira, G. S., Wu, C., Jensen, M., Kehlet, H., Botti, M., Boney, O., Haller, G., Grocott, M., Cook, T., Fleisher, L., Neuman, M., Story, D., Gruen, R., Bampoe, S., Evered, L., Scott, D., Silbert, B., van Dijk, D., Kalkman, C., Chan, M., Eckenhoff, R., Rasmussen, L., Eriksson, L., Beattie, S., Wijeysundera, D., Bartlett, R. J., Mcmonnies, R., Gerstl, J., Jay, M., Kishlyansky, D., Machina, M., Bobcock, M., Pearse, R., Mythen, M., Canet, J., Moller, A., Gin, T., Schultz, M., Pelosi, P., Gabreu, M., Futier, E., Creagh-Brown, B., Abbott, T., Klein, A., Corcoran, T., Dieleman, S., Diouf, E., Mcilroy, D., Bellomo, R., Shaw, A., Prowle, J., Karkouti, K., Billings, J., Mazer, D., Jayarajah, M., Murphy, M., Bartoszko, J., Sneyd, R., Morris, S., George, R., Moonesinghe, R., Shulman, M., Lane-Fall, M., Nilsson, U., Stevenson, N., Cooper, J. D., van Klei, W., Cabrini, L., Miller, T., Pace, N., Jackson, S., Buggy, D., Short, T., Riedel, B., Gottumukkala, V., Alkhaffaf, B., Johnson, M., Tramer, Martin, and Haller, Guy Serge Antoine

Subjects
medicine.medical_specialty, Consensus, Heart disease, Delphi Technique, Endpoint Determination, perioperative medicine, MACE, Cochrane Library, Perioperative Care, 03 medical and health sciences, Patient safety, cardiovascular events, outcome measures, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Anesthesiology, medicine, Humans, clinical trials, myocardial infarction, standardised endpoint, Intensive care medicine, Adverse effect, Clinical Trials as Topic, Perioperative medicine, ddc:617, business.industry, Cardiovascular Diseases, Perioperative Medicine, Research Design, Perioperative, medicine.disease, Clinical trial, Anesthesiology and Pain Medicine, business
Abstract

Background: Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials.Methods: We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity.Results: We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined.Conclusions: These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.

Published
2021

12. Perioperative Care of the Cancer Patient

Author

Carin A. Hagberg, Joseph L Nates, Berhard P Riedel, Vijaya N.R. Gottumukkala, Donal Buggy, Carin A. Hagberg, Joseph L Nates, Berhard P Riedel, Vijaya N.R. Gottumukkala, and Donal Buggy

Abstract

More than 80% of patients with cancer will need the services of anesthesiology and perioperative medicine, intensive care medicine, and pain management specialists during their cancer journey for diagnostic, therapeutic, and symptom management needs, as well as for the management of recurrent disease, secondary cancers, and ongoing non-oncologic surgical needs during survivorship. Perioperative Care of the Cancer Patient is today's most up-to-date, authoritative, comprehensive reference on the acute care of surgical patients with cancer, from a team of international experts in this emerging and dynamic specialty. Covers current clinical practice and perioperative care guidelines during the entire cancer journey for both adult and pediatric patients. Includes a diverse array of topics on cancer care, such as cancer epidemiology, cancer biology, ethics in cancer care delivery, value proposition in cancer care, opportunities and challenges with research programs in perioperative cancer care, application of big data and computational sciences in cancer medicine and care delivery, and the MD Anderson Cancer Center Moon Shots Program®. Discusses newer cancer therapies and their perioperative implications, functional assessment and prehabilitation, enhanced recovery programs in cancer care, challenges with novel cancer therapies in the care of the critically ill cancer patient, chronic and interventional pain management in patients with cancer, and more. An educational resource and clinical reference for surgeons, anesthesia practitioners, hospitalists, internists, pain physicians, intensivists, basic science researchers, and all clinicians involved in the acute care of surgical patients with cancer. Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.

Published
2022

13. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative : infection and sepsis

Author

Jonathan Barnes, Jennifer Hunter, Steve Harris, Manu Shankar-Hari, Elisabeth Diouf, Ib Jammer, Cor Kalkman, Andrew A. Klein, Tomas Corcoran, Stefan Dieleman, Michael P.W. Grocott, Michael G. Mythen, Paul Myles, Tang Joon Gan, Andrea Kurz, Phil Peyton, Dan Sessler, Martin Tramèr, Alan Cyna, Gildasio S. De Oliveira, Christopher Wu, Mark Jensen, Henrik Kehlet, Mari Botti, Oliver Boney, Guy Haller, Mike Grocott, Tim Cook, Lee Fleisher, Mark Neuman, David Story, Russell Gruen, Sam Bampoe, Lis Evered, David Scott, Brendan Silbert, Diederik van Dijk, Matthew Chan, Hilary Grocott, Rod Eckenhoff, Lars Rasmussen, Lars Eriksson, Scott Beattie, Duminda Wijeysundera, Giovanni Landoni, Kate Leslie, Bruce Biccard, Simon Howell, Peter Nagele, Toby Richards, Andre Lamy, Manoj Lalu, Rupert Pearse, Monty Mythen, Jaume Canet, Ann Moller, Tony Gin, Marcus Schultz, Paolo Pelosi, Marcelo Gabreu, Emmanuel Futier, Ben Creagh-Brown, Alexander Fowler, Tom Abbott, Andy Klein, David James Cooper, David McIlroy, Rinaldo Bellomo, Andrew Shaw, John Prowle, Keyvan Karkouti, Josh Billings, David Mazer, Mohindas Jayarajah, Michael Murphy, Justyna Bartoszko, Rob Sneyd, Steve Morris, Ron George, Ramani Moonesinghe, Mark Shulman, Meghan Lane-Fall, Ulrica Nilsson, Nathalie Stevenson, Jamie (DJ) Cooper, Wilton van Klei, Luca Cabrini, Tim Miller, Nathan Pace, Sandy Jackson, Donal Buggy, Tim Short, Bernhard Riedel, Vijay Gottumukkala, Bilal Alkhaffaf, Mark Johnson, Intensive Care Medicine, AII - Infectious diseases, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Tramer, Martin, and Haller, Guy Serge Antoine

Subjects
medicine.medical_specialty, Consensus, Delphi Technique, Endpoint Determination, Delphi method, perioperative medicine, Perioperative Care/standards, postoperative outcome, Surgical Wound Infection/therapy, Postoperative outcome, Perioperative Care, Sepsis, Perioperative medicine, sepsis, Core outcome measures, Respiratory Tract Infections/therapy, core outcome measures, infection, standardised endpoints, surgical site infection, Humans, Infection, Respiratory Tract Infections, Surgical Wound Infection, Anesthesiology and Pain Medicine, Anesthesiology, Outcome Assessment, Health Care, Endpoint Determination/standards, medicine, Attention, Standardised endpoints, Intensive care medicine, Infections/therapy, ddc:617, business.industry, Sepsis/therapy, Perioperative, anaesthesia, medicine.disease, Clinical trial, Clinical research, Quality and Patient Safety, business, Surgical site infection
Abstract

Background: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.Methods: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.Results: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.Conclusions: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.

Published
2019

14. Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia

Author

Andrea, Yap, Maria A, Lopez-Olivo, Julia, Dubowitz, Jonathan, Hiller, Bernhard, Riedel, and Donal, Buggy

Subjects
Survival Rate, Neoplasms, Anesthetics, Inhalation, Anesthesia, Intravenous, Humans, Anesthesia, Inhalation, Propofol, Anesthetics, Intravenous, Disease-Free Survival
Abstract

Cancer-related mortality, a leading cause of death worldwide, is often the result of metastatic disease recurrence. Anesthetic techniques have varying effects on innate and cellular immunity, activation of adrenergic-inflammatory pathways, and activation of cancer-promoting cellular signaling pathways; these effects may translate into an influence of anesthetic technique on long-term cancer outcomes. To further analyze the effects of propofol (intravenous) and volatile (inhalational gas) anesthesia on cancer recurrence and survival, we undertook a systematic review with meta-analysis.Databases were searched up to 14 November 2018. Comparative studies examining the effect of inhalational volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on cancer outcomes were included. The Newcastle Ottawa Scale (NOS) was used to assess methodological quality and bias. Reported hazard ratios (HRs) were pooled and 95% confidence intervals (CIs) calculated.Ten studies were included; six studies examined the effect of anesthetic agent type on recurrence-free survival following breast, esophageal, and non-small cell lung cancer (n = 7,866). The use of TIVA was associated with improved recurrence-free survival in all cancer types (pooled HR, 0.78; 95% CI, 0.65 to 0.94; P0.01). Eight studies (n = 18,778) explored the effect of anesthetic agent type on overall survival, with TIVA use associated with improved overall survival (pooled HR, 0.76; 95% CI, 0.63 to 0.92; P0.01).This meta-analysis suggests that propofol-TIVA use may be associated with improved recurrence-free survival and overall survival in patients having cancer surgery. This is especially evident where major cancer surgery was undertaken. Nevertheless, given the inherent limitations of studies included in this meta-analysis these findings necessitate prospective randomized trials to guide clinical practice.PROSPERO (CRD42018081478); registered 8 October, 2018.RéSUMé: OBJECTIF: La mortalité liée au cancer, une cause majeure de décès dans le monde entier, est bien souvent le résultat de la récurrence de la maladie métastatique. Les techniques anesthésiques ont des effets variés sur l’immunité naturelle et cellulaire, l’activation des voies adrénergiques inflammatoires, et l’activation des voies de signalisation cellulaire promouvant le cancer; ces effets pourraient se traduire dans une influence de la technique anesthésique sur les pronostics de cancer à long terme. Afin d’approfondir l’analyse des effets de l’anesthésie au propofol (voie intraveineuse) et par inhalation (gaz) sur la récurrence du cancer et la survie, nous avons entrepris une revue systématique avec méta-analyse.Nous avons réalisé des recherches dans les bases de données jusqu’au 14 novembre 2018. Les études comparatives examinant l’effet d’une anesthésie par inhalation et d’une anesthésie intraveineuse totale (TIVA) avec propofol sur les pronostics de cancer ont été incluses dans notre revue. L’échelle de Newcastle-Ottawa (NOS) a été utilisée pour évaluer la qualité méthodologique et le biais. Les rapports de risque (RR) rapportés ont été pondérés et les intervalles de confiance (IC) à 95 % calculés.Dix études ont été incluses; six études ont examiné l’effet du type d’agent anesthésique sur la survie sans récurrence après un cancer du sein, de l’œsophage et du cancer pulmonaire non à petites cellules (n = 7866). L’utilisation d’une TIVA était associée à une amélioration de la survie sans récurrence, tous types de cancer confondus (RR pondéré, 0,78; IC 95 %, 0,65 à 0,94; P0,01). Huit études (n = 18 778) ont exploré l’effet du type d’agent anesthésique sur la survie globale, l’utilisation d’une TIVA étant alors associée à une amélioration de la survie globale (RR pondéré, 0,76; IC 95 %, 0,63 à 0,92; P0,01).Cette méta-analyse suggère que l’administration d’une TIVA à base de propofol pourrait être associée à une amélioration de la survie sans récurrence et de la survie globale chez les patients subissant une chirurgie oncologique. Cette observation est particulièrement frappante dans les cas de chirurgie oncologique majeure. Toutefois, étant donné les lacunes inhérentes des études incluses dans cette méta-analyse, ces résultats nécessitent la réalisation d’études randomisées prospectives afin d’éclairer la pratique clinique. ENREGISTREMENT DE L’éTUDE: PROSPERO (CRD42018081478); enregistrée le 8 octobre 2018.

Published
2018

18. Correspondence

Author

Donal Buggy

Subjects
Anesthesiology and Pain Medicine
Published
2001

20. CONTRIBUTORS

Author

SALAHADIN ABDI, DONAL BUGGY, DANIEL B. CARR, JEREMY N. CASHMAN, RACHEL A. FARRAGHER, KATE FITZGERALD, HENRY FRIZELLE, DOMINIC HARMON, JAMES HELSTROM, and ROBERT W. HURLEY

Published
2006

22. Corrigendum

Author

Donal Buggy

Subjects
Pharmacology, Pharmacology (medical), Corrigendum
Published
2010

23. Anesthesiology

Author

Donal Buggy

Subjects
Anesthesiology and Pain Medicine, General Medicine
Published
2008

25. Reply

Author

Donal Buggy

Subjects
Anesthesiology and Pain Medicine, General Medicine
Published
1996

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