Colorectal Disease. 2020;00:1–18. wileyonlinelibrary.com/journal/codi
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During the early phases of the COVID-19 pandemic there was un-certainty about the impact of perioperative SARS-CoV-2 on surgical
patients and a growing scarcity of intensive care capacity [1,2]. Guidelines emerged which recommended changing anastomotic practice in favour of forming a defunctioning stoma or end stoma in patients who would have previously only had an anastomosis [3–6]. †
© 2020 The Association of Coloproctology of Great Britain and Ireland †A complete list of the investigators is included in Appendix 1.
Aneel Bhangu, NIHR Global Health Research Unit on Global Surgery, Heritage Building, University of Birmingham, UK.
Email: a.a.bhangu@bham.ac.uk
National Institute for Health Research Global Research Unit, Grant/Award Number: NIHR 16.136.79
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic.
This was an international cohort study of patients undergoing elective resec-tion of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The pri-mary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data.
-Surgeons need to further mitigate against both SARS-CoV-2 and anasto-motic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks.
The first anticipated benefit was to diminish the severity and volume of postoperative anastomotic leaks during a time when the impact of the novel coronavirus was unknown [7]. The second was to reduce the requirement for intensive care when hospital resources were being redirected to the pandemic response [8]. The third was to re-duce complications that lead to increased length of hospital stay, in order to release bed space and minimize the risk of nosocomial infec-tion [9,10].
Subsequent data have confirmed the detrimental effect of
Despite outbreaks, cancer surgery must continue in order to prevent an overwhelming number of delayed operations, a possible increase in emergency procedures and a significant decline in population health [12].
The extent of new stoma formation during the first phases of the pandemic and the subsequent patient-related outcomes are unknown. The impact of anastomotic leak and postoperative SARS-CoV-2 infection on mortality are also unknown. This study aimed to fill these knowledge gaps and to produce patient-level outcome data that would inform patient selection and informed consent.
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This was a planned specialty analysis of adult patients undergoing elective colonic and rectal cancer resection in a prospective inter-national multicentre cohort study of patients undergoing elective surgery without preoperative suspicion of SARS-CoV-2 [13]. Study approvals for participating hospitals were secured by local principal investigators before entry into the study and data collection. The study protocol was either registered as a clinical audit with institu-tional review or a research study obtaining ethical committee ap-proval, dependent on local and national requirements. Data were collected online and stored on a secure server running the Research University of Birmingham, UK. Any hospital performing elective colon or rectal cancer surgery in countries affected by the COVID-19 pandemic was eligible to participate. Hospitals were required to collect data on consecutive eligible patients from the date of their first recorded case of COVID-19 until 19 April 2020.
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-tive colonic or rectal cancer resectional surgery with cura-tive intent were eligible. Palliative operations, including those where
the tumour was left in situ
-eligible patients were identified from multidisciplinary team
meetings, operating lists and outpatient or telemedicine clinics. The day of surgery was defined as day zero, with patients followed up for 30 days postoperatively using routine follow-up pathways. Patients who had an operation for suspected cancer which was subsequently shown to be a preinvasive lesion after histological
in situ
included in this study. However, patients who had an operation for a suspected cancer but who had a histologically benign lesion were excluded. Elective surgery was defined as any surgery booked in Patients who were suspected of having, or confirmed to have, -geal swab and quantitative reverse transcription polymerase chain were excluded from these analyses.
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Baseline patient characteristics included age, sex and American [16]. Age was collected as deciles of years as a categorical variable.
stage prior to surgery, or neoadjuvant treatment. The TNM stage was used to calculate the patient’s baseline cancer disease stage. Disease stages were grouped for analysis as Stage I or Stage II versus Stage III or Stage IV. For patients with cancers involving the rectum,
variables collected included the operative procedure performed, if a defunctioning or end stoma was formed, the operative approach
technique was used for the anastomosis, where applicable. We did not specify the precise nature of minimally invasive surgery as there are many variants, but we know from previous international studies For analysis, operative procedures were grouped anatomically into right resection, left resection, rectal resection and total/subtotal/
Mortality associated with anastomotic leak and postop-erative SARS-CoV-2 during the COVID-19 pandemic was extremely high. A relatively small change in stoma practice was seen. Surgeons need to robustly mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during future waves of COVID-19, based on patient, opera-tive and organizational factors.
panproctocolectomy. A full list of operative procedures is included in Table S1 in the Supporting Information.
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The primary outcome measure was mortality within the 30 days following surgery. Secondary outcome measures were anastomotic postoperative SARS-CoV-2 infection and total length of hospital stay up to 30 days after surgery. Postoperative SARS-CoV-2 infec-tion was defined as a positive swab or CT thorax in line with locally implemented protocols, or a clinical diagnosis of symptoms in keep-ing with COVID-19 in patients where no swab test or CT scan was available.
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Data were collected on the intraoperative decision on stoma forma-tion. Where patients had a stoma, surgeons were asked if this was their ‘normal practice’ or a ‘change in practice due to COVID-19’. The group with a stoma created as a change in practice were labelled ‘COVID-end-stoma’ or ‘COVID-defunctioning-stoma’ for tables and analyses. If the patient had a stoma formed and the surgeon indi-cated a ‘change in practice due to COVID-19’, they were asked to list
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Prepandemic data on colorectal cancer surgery were obtained from Hemicolectomy Audit [19–21] and the 2017 Left Colon, Sigmoid
rectal cancer were used for comparison with the equivalent cohort undergoing surgery during the pandemic. These data provided a contemporaneous and detailed comparison of case selection and outcomes during the pandemic and prepandemic periods. Data were not presented in these studies for total or subtotal colectomy, so no comparison was made with these operation types. TNM staging data therefore comparison was not made in that field.
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The study was conducted according to guidelines set by the
square test was used to compare differences in categorical data
apart from when cell sizes were small, when Fisher's exact tests were used. Continuous nonparametric data are presented as medi-ans and interquartile ranges and median differences between groups were compared using the Mann–Whitney U-test. Missing data are included in summary tables.
For the primary outcome of 30-day mortality, a multilevel lo-gistic regression was used to evaluate the impact of postoperative SARS-CoV-2 and anastomotic leak on death after surgery,
summa-model also included clinically plausible preoperative and intraoper-ative factors in order to adjust for covariates and reduce the risk
-to compare outcomes for those with a COVID-s-toma and those without. Similar methods were used to compare pandemic data with published prepandemic data. Analysis was performed used Stata SE
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This analysis included 2073 patients undergoing resection of a
co
-radiotherapy.
-imally invasive surgery was attempted with conversion to an open had a stapled anastomosis. The lead surgeon in the majority of
op-|
Table 2. This contrasts with the prepandemic era when a colorectal where a stoma was formed. More COVID-end-stomas were formed in patients undergoing rectal resections, in those who had an open approach to surgery and in those who received either no neoadju-is also reflected in an increase in the number of end stoma formations
-crease of formation of anastomosis without a defunctioning stoma
-pared with all stomas is shown in Table S3.
n n n n n n % n % n % n % Sex Female 16 Male 381 232 31 ASA grade 1–2 686 36 269 123 11 Missing 1 0 0 96 11 268 187 16 20 Disease stage I–II 216 33 III 181 78 9 IV 31 28 68 Neoadjuvant radiotherapya Short course 89 0 0 Long course 1 None 33 Approach Laparoscopic 231 19 Open 298 109 Conversion 31 27 Anastomotic technique Stapled 298 619 30 Hand sewn 36 No anastomosis 37 30 13 Missing 3 8 0 Seniority Colorectal consultant 263 732 38 Colorectal trainee 61 3
General surgery consultant 126 6
General surgery trainee 23 18 0 0
Missing 2 6 0
Abbreviation: ASA, American Society of Anesthesiologists.
There were slight but nonsignificant differences in patients who -n % n % Overall New COVID-stomas 27/2073 63/2073 Sex Female 11/837 Male 16/1236 39/1236 ASA grade 1–2 31/966 9/933 30/933 Operation Right resection Left resection 2/367 7/367 Rectal resection Total/subtotal/ panproctocolectomy 0 Disease stage I–II 11/838 31/838 III IV 3/133 2/133 Neoadjuvant radiotherapya Short course 3/89 1/89 Long course 9/206 None Approach Minimally invasive Open Minimally invasive converted to open 1/102 3/102 Anastomotic techniqueb
Stapled N/A N/A
Hand sewn N/A N/A
Seniority
Colorectal consultant
Colorectal trainee 11/133 3/133
General surgery consultant 2/322 11/322
General surgery trainee Note:
COVID-19 pandemic out of the total number of patients who had an operation in each group.
aOf patients who had an operation involving the rectum. bOf patients who had an anastomosis.
formed due to COVID-19 in relation to all patients undergoing surgery
no difference in outcomes was observed in patients undergoing
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The reason for change in practice was explored in patients who
19; n
-common reasons reported for formation of COVID-stoma were
one cited ‘very difficult working conditions of full PPE’ as the rea-sons for COVID-stoma.
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-tients had an anastomotic leak. Mortality rates are presented in Figure 2, and show an increasing relationship with both anastomotic leak and SARS-CoV-2 infection. In risk-adjusted analyses, significant predictors of 30-day mortality were postoperative SARS-CoV-2, anastomotic leak, male sex, age over 70 years, cancer disease Stage
Overall RIGHT SIDE Normal practice COVID-stoma n = 11/724 (1.5%) COVID-stoma n = 9/367 (2.5%) COVID-stoma COVID-stoma n = 69/935 (7.4%) n = 1/47 (2.1%)
Normal practice Normal practice Normal practice
n = 724 n = 713/724 (34.9%) (98.5%) n = 358/367 (97.5%) n = 866/935 (92.6%) n = 46/47 (97.9%) LEFT SIDE n = 367 (17.7%) RECTUM n = 935 (45.1%) TOTAL/SUBTOTAL n = 47 (2.3%) n = 2073 Anastomosis n = 1366 (65.5%) Anastomosis + defunctioning stoma End stoma n = 372 (17.7%) Anastomosis 676 (94.8%) Anastomosis + defunctioning stoma End Stoma 9 (1.3%) 28 (3.9%) Anastomosis 316 (88.2%) Anastomosis + defunctioning Stoma End Stoma 19 (5.3%) 23 (6.5%) Anastomosis 350 (40.4%) Anastomosis + defunctioning stoma End stoma 306 (35.3%) 210 (24.3%) Anastomosis 23 (50.0%) Anastomosis + defunctioning stoma End stoma 11 (23.9%) 12 (26.1%) Anastomosis + defunctioning stoma End stoma 1 (9.1%) 10 (90.9%) Anastomosis + defunctioning stoma End stoma 2 (22.2%) 7 (77.8%) Anastomosis + defunctioning stoma End stoma 24 (34.8%) 45 (65.2%) End stoma 1 (100%) n = 335 (16.8%) P n % n % Anastomotic leaka No 1627 0.390 Yes 2 Intensive care No Yes 26 Death No 89 1.000 Yes 37 1 Postoperative SARS-CoV-2 No 1909 86 Yes Length of stay b 0.270
aOf patients who had an anastomosis. b
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Pandemic data are compared with prepandemic data from ESCP -tween patient characteristics across different operations. Overall,
Outcomes following surgery during the pandemic included fewer anastomotic leaks and admissions to critical care; however, mortality
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Mortality associated with an anastomotic leak and postoperative SARS-CoV-2 during the first waves of the COVID-19 pandemic was extremely high. A small change in stoma practice was observed, they would usually have had an anastomosis only. Although those patients did not suffer any adverse outcomes, those measures alone did not reduce the overall complication rates seen in this study. In comparison with published mortality data following perioperative SARS-CoV-2 infection alone, the relative risk of death was almost
Comparison with previous ESCP cohort data identifies some of the selection bias that took place during these phases of the pan-demic. There was an increased use of stapled anastomosis, fewer
admissions to intensive care and a shorter length of stay. These all suggest efforts by surgeons and patients to reduce the duration of surgery, resource usage and hospital stay. Rectal cancer patients un-dergoing surgery seemed to be fitter than in data from the ESCP audits, with a higher proportion of patients of ASA grades 1–2. Slightly fewer patients underwent neoadjuvant therapy compared with before the pandemic, which suggests a greater element of de-layed surgery or ‘watch and wait’ strategies during the pandemic. Outcomes from patients who had neoadjuvant therapies and were either delayed or did not have surgery are awaited. There may be an increased flow of patients ‘postpandemic’, both needing surgery and needing monitoring, who will require additional support from already strained surgical systems.
This study had limitations. First, this was an observational study in the first phase of the pandemic, where guideline implemen-tation was incomplete. Data on implemenimplemen-tation of guidelines by each hospital or country were not captured in this study. Second, the absolute change in practice presented was small, so firm con-clusions cannot be drawn around the safety of the wider adoption of risk-averse practices. Third, comparison with the prepandemic ESCP audit dataset may be biased through undetected patient-, hospital- and country-level differences that could preclude direct comparison, therefore the results must be interpreted with caution and firm conclusions should not be drawn. Fourth, data were not presented for patients who had surgery delayed due to COVID-19 or had an alternative treatment strategy. We therefore present an incomplete picture of the care of colorectal cancer patients during the pandemic. Fifth, change in practice to COVID-stoma was re-ported by the surgeon and is therefore subjectively rere-ported. We attempted to overcome this by comparing the total stoma rate with prepandemic rates, showing an increased rate of stoma formation during the pandemic. Sixth, despite guidance and concerns around
All patients
Overall with anastomosis End stoma
n = 1738 (83.8%) n = 335 (16.2%) n = 2073 Alive n = 2035 (98.2%) Died n = 38 (1.8%) Alive n = 1705 (98.1%) Died n = 33 (1.9%) SARS-CoV-2 n = 64 (3.7%) Alive n = 51 (79.7%) Died n = 13 (20.3%)
No anastomotic leak Anastomotic leak n = 51 (79.7%) n = 13 (20.3%) Alive n = 43 (84.3%) Died n = 8 (15.7%) No anastomotic leak n = 1601 (95.6%) Alive n = 1587 (99.1%) Died n = 14 (0.9%) Alive n = 8 (61.5%) Died n = 5 (38.5%) Anastomotic leak n = 73 (4.4%) Alive n = 67 (91.8%) Died n = 6 (8.2%) No infection n = 1674 (96.3%) SARS-CoV-2 n = 14 (4.2%) Alive n = 1654 (98.8%) Died n = 20 (1.2%) Alive n = 12 (85.7%) Died n = 2 (14.3%) No infection n = 321 (95.8%) Alive n = 318 (99.1%) Died n = 3 (0.9%) Alive n = 330 (98.5%) Died n = 5 (1.5%)
aerosolization, this study showed that laparoscopic approaches continued. The reasons for this, including surgeon and patient atti-tudes, deserve further exploration by way of additional qualitative research. Finally, although case selection and more elective stomas can potentially reduce postoperative risks, further robust strategies are needed to mitigate against morbidity and mortality and further exploration is required.
Clear data and safe strategies are needed to continue to provide safe surgery during future pandemic waves. This study highlights several patient, operative and organizational factors that may bring benefit and need further testing. At a patient level, selection of fitter patients, who will benefit most from curative surgery during peaks of pandemics, is logical. This has been previously recommended to both conserve critical care capacity and avoid exposing high-risk patients to nosocomial SARS-CoV-2 transmission [3,9]. At an opera-tive level, the avoidance of leaks seems paramount. Forming stomas alone is not necessarily the solution, as they carry their own risks and morbidity. Selecting lower-risk patients for anastomosis, use of defunctioning stomas and more liberal use of end stomas in high-risk patients might be best supported through formal high-risk stratifi-prevention of postoperative SARS-CoV-2-related infections is par-amount. This seems best approached by identifying preoperative, providing COVID-19-free surgical pathways. Both of these areas re-quire further evidence to best define exactly which measures they
-mated 3 000 000 cancer operations postponed around the world [12], and more accruing during second waves, efficient measures to safely discharge patients early and protect them from the risk of in-hospital transmission should continue.
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Data-sharing requests will be considered by the management group upon written request to the corresponding author. If agreed, de-identified participant data will be available, subject to a data-sharing agreement.
There are no conflicts of interest to declare.
This report was funded by a National Institute for Health Research aid from the UK Government to support global health research, The Association of Coloproctology of Great Britain and Ireland, Bowel & Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society; European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland and Yorkshire Cancer Research. The funders
P n % Anastomotic leak No – – Yes 11/93 9.21 6.01 No – – Yes 16.90 7.86–36.38 <70 – – 2.39 2.87 1.32–6.20 Sex Female 7/837 – Male 31/1236 ASA gradea 1–2 – – 2.23 0.76–3.26 0.223
Disease stage I–II 17/1288 –
III 1.76 2.00 0.088
IV 6/132 1.38–9.19 1.16–10.21
Operation Right resection – –
Left resection 6/367 1.32
Rectal resection 1.60 0.302
Total/subtotal/ panproctocolectomy
7.39 9.06
Statistically significant P values are indicated in bold.
P-P P Se x Se x Se x Mal e 0. 67 6 Mal e 0. 22 8 Mal e 0. 73 8 Fe m al e Fe m al e Fe m al e 0. 31 2 0.0 61 A SA g ra de A SA g ra de A SA g ra de 1– 2 1– 2 0. 19 8 1– 2 Ap pr oa ch D is ea se s ta ge D is ea se s ta ge Mi nim al ly in va si ve I–I I I–I I Op en III III Co nv er si on IV IV Op er at io n Ap pr oa ch N eo ad ju va nt r ad io th er ap y An as to m os is Mi nim al ly in va si ve Sh or t c ou rs e A na st om os is + de fu nc ti on Op en Lo ng c ou rs e En d s to m a Co nv er si on No ne A na st om ot ic t ec hn iq ue a Op er at io n Ap pr oa ch St ap le d An as to m os is Mi nim al ly in va si ve H an d s ew n A na st om os is + de fu nc ti on Op en En d s to m a Co nv er si on
P-P P Se ni or it y A na st om ot ic t ec hn iq ue a Op er at io n C ol or ec ta l su rg eo n St ap le d An as to m os is C ol or ec ta l tr ai ne e H an d s ew n A na st om os is + de fu nc ti on G en er al su rg eo n En d s to m a G en er al su rg ic al tr ai ne e A na st om ot ic le ak a Se ni or it y A na st om ot ic t ec hn iq ue a No C ol or ec ta l su rg eo n St ap le d 0. 99 8 Ye s C ol or ec ta l tr ai ne e H an d s ew n G en er al su rg eo n G en er al s ur gi ca l tr ai ne e In te ns iv e c ar e A na st om ot ic le ak a Se ni or it y No No C ol or ec ta l su rg eo n 0.0 87 Ye s Ye s C ol or ec ta l tr ai ne e G en er al su rg eo n G en er al su rg ic al tr ai ne e De at h In te ns iv e c ar e A na st om ot ic le ak a No No No Ye s Ye s Ye s
had no role in study design, data collection, analysis and interpreta-tion or writing of this report. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the UK Department of Health and Social Care.
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Elizabeth Li*, James C. Glasbey*, Dmitri Nepogodiev*, Joana F. F. Simoes*, Omar M. Omar, Mary L. Venn, Jonathan P. Evans, Kaori Futaba, Charles H. Knowles, Ana Minaya-Bravo, Helen Mohan, Manish Chand, Peter Pockney, Salomone Di Saverio, Neil Smart, Abigail Vallance, Dale Vimalachandran, Richard J. W. Wilkin, Aneel
Aneel Bhangu.
Kwabena Siaw-Acheampong, Ruth A. Benson, Edward Bywater, Daoud Chaudhry, Brett E. Dawson, Jonathan P. Evans, James C. Glasbey, Rohan R. Gujjuri, Emily Heritage, Conor S. Jones, Sivesh K. Kamarajah, Chetan Khatri, Rachel A. Khaw, James M. Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S. Mann, Ella J. Marson, Kenneth A. McLean, Siobhan C. Mckay, Emily C. Mills, Dmitri Nepogodiev, Gianluca Pellino, Maria Picciochi, Elliott H. Taylor, Abhinav Tiwari, Joana F. F. Simoes, Isobel M. Trout, Mary L. Venn, Richard J. W. Wilkin, Aneel Bhangu.
Bravo*, Jonathan P. Evans, Gaetano Gallo, Susan Moug, Francesco Pata, Peter Pockney, Salomone Di Saverio, Abigail Vallance, Dale Vimalchandran.
Michel Adamina, Adesoji O. Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeiers, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P. Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K. Bankhead-Kendall, Emma Barlow, David Beard, Ruth A. Benson, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A. Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J. Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F. Cunha, Giana H. Davidson, Anant Desai, Salomone Di Saverio, Thomas M. Drake, John G. Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J. Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Grecinos, Ewen A. Griffiths, Madalegna Gründl, Constantine Halkias, Ewen M. Harrison, Intisar Hisham, Peter J. Hutchinson, Shelley Hwang, Arda Isik, Michael D. Jenkinson, Pascal Jonker, Haytham M. A. Kaafarani, Debby Keller, Angelos Kolias, Schelto Kruijff, Ismail Lawani, Hans Lederhuber, Sezai Leventoglu, Andrey Litvin, Andrew Loehrer, Markus W. Löffler, Maria Aguilera Lorena, Maria Marta Madolo, Piotr Major, Janet Martin, Hassan N. Mashbari, Dennis Mazingi, Symeon Metallidis, Ana Minaya-Bravo, Helen M. Mohan, Rachel Moore, David Moszkowicz, Susan Moug, Joshua S. Ng-Kamstra, Mayaba Maimbo, Ionut Negoi, Milagros Niquen, Faustin Ntirenganya, Maricarmen Olivos, Kacimi Oussama, Oumaima Outani, Marie Dione Parreno-Sacdalanm, Francesco Pata, Carlos Jose Perez Rivera, Thomas D. Pinkney, Willemijn van der Plas, Peter Pockney, Ahmad Qureshi, Dejan Radenkovic, Antonio Ramos-De la Medina, Keith Roberts, April C. Roslani, Martin Rutegård, Irène Santos, Sohei Satoi, Raza Sayyed, Andrew Schache, Andreas A Schnitzbauer, Justina O. Seyi-Olajide,
Neil Sharma, Richard Shaw, Sebastian Shu, Kjetil Soreide, Antonino Spinelli, Grant D Stewart, Malin Sund, Sudha Sundar, Stephen Tabiri, Philip Townend, Georgios Tsoulfas, Gabrielle H. van Ramshorst, Raghavan Vidya, Dale Vimalachandran, Oliver J. Warren, Duane Wedderburn, Naomi Wright, EuroSurg,
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Emmanuel K., Grechenig M., Gruber R., Harald M., Öhlberger L., Barbados: Barker D., Boyce R., Doyle A., Eastmond A., Gill R., O’Shea M., Padmore G.*, Paquette N., Phillips E., St John S., Walkes
Cyprus: Frantzeskou K., Gouvas N.*, Kokkinos G., Papatheodorou
Denmark: Ebbehøj A. L., Krarup P., Schlesinger N., Smith H.*
Egypt: Al Sayed M., Ashoush F.*, Elazzazy E., Essam E., Eweda M., Hassan E., Metwalli M., Mourad M., Qatora M. S., Sabry A.*,
Abdeldayem H., Abdelkader Salama I.*, Balabel M., Fayed Y., Sherif
Germany: Bork U.*, Fritzmann J., Praetorius C., Weitz J., Welsch
Greece: Antonakis P., Contis I., Dellaportas D., Gklavas A., Konstadoulakis M., Memos N.*, Papaconstantinou I.*, Polydorou A.,
Arkadopoulos N., Danias N., Economopoulou P., Frountzas M., Kokoropoulos P., Larentzakis A., Michalopoulos N.*, Parasyris S.,
Chatzikomnitsa P., Efthimiou M., Giaglaras A., Kalfountzos C.*, Koukoulis G., Ntziovara A. M., Petropoulos K., Soulikia K., Tsiamalou
Hong Kong: Futaba K.*, Ho M. F., Hon S. F., Mak T. W. C., Ng S.
India: Bhat G. A., Chowdri N. A., Mehraj A.*, Parray F., Shah Z. A., Bali R., Bhat M. A., Laharwal A., Mahmood M., Mir I., Mohammad
Ireland: Aremu M.*, Canas-Martinez A., Cullivan O., Murphy C., M.*, Daly A., Fleming C.*, Jordan P., Killeen S., Lynch N., O’Brien S., Larkin J. O.*, McCormick P., Mehigan B. J., Mohan H., Shokuhi P., Creavin B., Earley H., Elliott J. A.*, Gillis A. E., Kavanagh D. O., Neary P. C., O’Riordan J. M., Reynolds I. S., Rice D., Ridgway P. F., Umair M.,
C., Alemanno G., Bartolini I., Bergamini C., Bruscino A., De Vincenti R., Di Bella A., Fortuna L., Maltinti G., Muiesan P.*, Prosperi P.*,
Di Franco G., Furbetta N., Gianardi D., Guadagni S., Morelli L.*, Anania G.*, Carcoforo P.*, Chiozza M., De Troia A., Koleva Radica
A.*, Montori G., Moras L., Olivieri M.; Feo C. F., Perra T.*, Porcu
Carbone F., Delrio P.*, Di Lauro K., Fares Bucci A., Rega D.*, Spiezio
A., Cozza V., D’Ugo D., De Simone V., Litta F., Lorenzon L., Marra A. A., Marzi F., Parello A., Persiani R., Ratto C., Rosa F., Scrima O.,
University, Department of Biomedical Sciences, Pieve Emanuele
Capezzuoli L., Di Martino C., Ipponi P., Linari C., Montelatici M.,
Cicerchia P. M., Cirillo B., De Toma G., Fiori E., Fonsi G. B., Iannone I., La Torre F., Lapolla P.*, Meneghini S., Mingoli A., Sapienza P., Zambon
D., Di Maria Grimaldi S., Donati D., Gelarda E., Giraudo G., Giuffrida
Madagascar: Rasoaherinomenjanahary F.*, Razafindrahita J. B., Malaysia: Hamdan K. H., Ibrahim M. R., Tan J. A., Thanapal M.
Hussain A. H., Mohamed Sidek A. S., Mohd Yunus M. F., Soh J. Y.,
Mexico: Buerba G. A., Mercado M. Á.*, Posadas-Trujillo O. E.,
Morocco: Amrani L., El Ahmadi B., El Bouazizi Y., Majbar A.
Netherlands: Hompes R.*, Meima-van Praag E. M., Pronk A. J.
Abdur-Rahman L.*, Adeyeye A.*, Bello J., Olasehinde O., Popoola A.
Fernandes U., Ferreira C.*, Guidi G., Marçal A., Marques R., Martins
de Sá T., Costa M. J. M. A., Fernandes V., Ferraz I., Lima da Silva C., Lopes L., Machado N., Marialva J., Nunes Coelho M., Pereira C., Ribeiro A., Ribeiro C. G., Santos R., Saraiva P., Silva R., Tavares A. C., Amaral M. J., Andrade R., Camacho C., Costa M., Lázaro
P., Manso M. I., Martins dos Santos G., Martins R., Morais H.*, Pereira R., Revez T., Ribeiro R., Ribeiro V. I., Soares A. P., Sousa S.,
Figueiredo de Barros I., Frade S., Gomes J., Kam da Silva Andrade A., Pereira Rodrigues A., Pina S., Silva N.*, Silveira Nunes I., Sousa Costeira B., Cunha C., Garrido R.*, Miranda P., Peralta Ferreira M.,
Romania: Bezede C., Chitul A., Ciofic E., Cristian D., Grama F.*
Russia: Garmanova T., Kazachenko E., Markaryan D., Rodimov S.,
King Abdullah International Medical Research Center, Ministry of Khayal K., Alhassan N., Alobeed O., Alshammari S., Bin Nasser A.*, Bin
South Africa: Almgla N.*, Boutall A., Herman A., Kloppers C.*, Nel
T.*, Santanach C., Serrano-Navidad M., Sorribas Grifell M., Vives R.
De Lacy F. B., Lacy A. M.*, Otero A., Turrado-Rodriguez V.*, Valverde
J.M.*, Pizarro M. J., Saez Carlin P., Sánchez del Pueblo C.,
Sánchez-M., De Miguel Ardevines M. D. C., Duque-Mallén V.*, Gascon Ferrer I., González-Nicolás Trébol M. T., Gracia-Roche C., Herrero Lopez M., Martinez German A., Matute M., Sánchez Fuentes N.,
Sánchez-Pacheco Sánchez D., Pérez-Saborido B., Sanchez Gonzalez J., Tejero-Morales L., Cintas Catena J., Gomez-Rosado J.*, Oliva Mompean F.,
Tellez L.*, Heras Aznar J.*, Maté P., Ortega Vázquez I.*, Picardo A. L.,
Sweden: Älgå A.*, Heinius G., Nordberg M., Pieniowski E.
Switzerland: Arigoni M., Bernasconi M., Christoforidis D.*, Di
E., Altintoprak F.*, Cakmak G., Çelebi F., Demir H., Dikicier E., Firat
UK: Agilinko J., Ahmeidat A., Bekheit M.*, Cheung L. K., Kamera Al-Mohammad A., Ali S., Ashcroft J., Baker O., Coughlin P., Davies R. J.*, Kyriacou H., Mitrofan C. G., Morris A., Raby-Smith W., Rooney S., Angelou D., Choynowski M., McAree B.*, McCanny A., Neely D.
E., Manu N., Martin E., Roy Mahapatra S., Serevina O. L., Smith C.,
Abubakar A.*, Akhter Rahman M. M., Chan E., O’Brien H., Sasapu
Ibrahim S., Maw A.*, Mithany R., Morgan R.*, Sundaram Venkatesan
Bhatti M. I., Boyd-Carson H., Elsey E., Gemmill E., Herrod P.*, Jibreel
S., Khan A. H., Khan F., Mukherjee S.*, Patel M., Sarigul M., Singh S. Evans J., Humes D.*, Jackman J., Koh A., Lewis-Lloyd C., Oyende O.,
Chung E., Hagger R., Hainsworth A., Karim A., Owen H., Ramwell A., USA: Haynes A.*, Hill C., Leede E., McElhinney K., Olson K. A.,
R., Long C., Malapati H., Margalit A., Rapaport S., Rose J., Stevens
