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51. Long-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development

Author

Laura Licchetta, Luca Vignatelli, Francesco Toni, Andrea Teglia, Laura Maria Beatrice Belotti, Lorenzo Ferri, Veronica Menghi, Barbara Mostacci, Lidia Di Vito, Francesca Bisulli, and Paolo Tinuper

Subjects
Cohort Studies, Malformations of Cortical Development, Drug Resistant Epilepsy, Epilepsy, Seizures, Humans, Anticonvulsants, Neurology (clinical)
Abstract

ObjectiveTo evaluate the long-term outcomes of patients with epilepsy and malformations of cortical development (MCD).MethodsWe conducted a historical cohort study of patients with epilepsy and MCD due to impaired neuronal migration and postmigration organization with a follow-up period of ≥5 years. For each patient, MCD was classified after accurate neuroimaging reappraisal by an expert neuroradiologist. The primary outcome was remission, defined as a period of seizure freedom ≥5 years at any time from epilepsy onset. We used Kaplan-Meier estimates for survival analysis and univariate and multivariate Cox regression analyses to evaluate baseline variables as possible factors associated with remission.ResultsThe cohort included 71 patients (M/F 31/40) with a 17-year median follow-up (1,506 person-years). About half (49.3%) had heterotopia, 35.2% polymicrogyria, 7% lissencephaly, and 8.5% the combination of 2 MCD. The mean age at seizure onset was 12.4 ± 7.2 years. Intellectual disability and neurologic deficits were observed in 30.4% and 40.9%, respectively. More than 60% of patients had refractory epilepsy. In 3 patients who underwent epilepsy surgery, MCD diagnosis was confirmed by histology. At the last visit, 44% of patients had been seizure-free during the previous year, but none of them had stopped antiseizure medication. Thirty patients achieved remission (42.2%) at some point in their disease history, whereas 41 individuals (57.8%) had never been in remission for ≥5 years. The cumulative remission rate was 38% by 20 years from inclusion. In the Cox model, unilateral distribution of MCD (hazard ratio [HR] 2.68, 95% CI 1.04–6.92) and a low seizure frequency at onset (HR 5.01, 95% CI 1.12–22.5) were significantly associated with remission.DiscussionPatients with epilepsy and MCD showed a remission rate of 38% by 20 years from onset. Unilateral distribution of the MCD is associated with a 3-fold probability of achieving remission. About 40% of patients showed a drug-sensitive condition with risk of relapse during their epilepsy course.Classification of EvidenceThis study provides Class II evidence that in patients with epilepsy and MCD, unilateral MCD and low seizure frequency at onset are associated with achieving epilepsy remission.

Published
2022

52. Esophageal and gastric malignancies after bariatric surgery: a retrospective global study

Author

Chetan Parmar, Roxanna Zakeri, Mohamed Abouelazayem, Thomas H. Shin, Ali Aminian, Tala Mahmoud, Barham K. Abu Dayyeh, Melissa Y. Wee, Laura Fischer, Freek Daams, Kamal Mahawar, Carlos Sosa Gallardo, Cataldo Agustin, Fernando Wright, Ignacio Fuente, Miguel Carbajo, Patricio Cal, Jacob Chisholm, Lilian Kow, Michael H.L. Tan, Philip Gan, Sivakumar Gananadha, Daniel M. Felsenreich, Gerhard Prager, Chris Matthys, Jacques M. Himpens, Marc A.M.R.M. Focquet, Almino Ramos, Manoel Galvano Nato, Thiago Vidal, Amin Andalib, Aya Siblini, Lorenzo Ferri, Lina Abdarabo, Yehonatan Nevo, Radu Pescarus, Wah Yang, Hosam Hamed, Arnaud Liagre, Damien Bergeat, De Montrichard Marie, Francesco Martini, François Regis, Laurent Genser, Mehdi Skalli, Marius Nedelcu, Milan Smejkal, Radwan Kassir, Regenet Nicolas, Christine Stier, Dan-Sebastian Nedelcut, Grigorios Christodoulidis, Amar Vennapusa, Mohammad Kermansaravi, Asnat Raziel, Nasser Sakran, Alberto Oldani, Cristian Eugeniu Boru, Fouzia Mécheri, Francesca Ciccarese, Giovanni Carlo Cesana, Mario Musella, Matteo Uccelli, Mirto Foletto, Pasquale Auricchio, Stefano Olmi, Yosuke Seki, Anne Kasteleijn, Gerhard Van 'T Hof, Jan A. Apers, Judith W.H. Hart, Justin S.L. Van De Sande, Marijn Takkenberg, Pierre B.G.M. Feskens, Rob Snoekx, Victor D. Plat, Jorunn Sandvik, Piotr Kalinowski, Celso Nabais, Ahmed Z. Al-Bahrani, Mohammad Al Zoubi, Carla Bettonica, Javier Osorio, Javier Tejedor-Tejada, Lourdes M. Sanz, Marta Cuadrado, Rajesh Gianchandani Moorjani, Fringeli Yannick, Michel Suter, Yves Borbély, Zehetner Joerg, Juan S. Barajas-Gamboa, Matthew Kroh, Aaron P. Kisiel, Anna Kamocka, Arul Immanuel, Bruno Sgromo, Bussa Gopinath, David Khoo, Samrat Mukherjee, Dimitrios Pournaras, Tim Underwood, Ewen A. Griffiths, Glenn V. Miller, Helen Jaretzke, Jan Dmitrewski, Martin S. Wadley, Ragad Al-Housni, Richard S. Gillies, Rishi Singhal, Shaun R. Preston, Steven John Robinson, William J. Hawkins, Marco Adamo, Mohamed El Kalaawy, James Gossage, Christopher B. Crawford, Veeravich Jaruvongvanich, Parmar, C., Zakeri, R., Abouelazayem, M., Shin, T. H., Aminian, A., Mahmoud, T., Abu Dayyeh, B. K., Wee, M. Y., Fischer, L., Daams, F., Mahawar, K., Gallardo, C. S., Agustin, C., Wright, F., Fuente, I., Carbajo, M., Cal, P., Chisholm, J., Kow, L., Tan, M. H. L., Gan, P., Gananadha, S., Felsenreich, D. M., Prager, G., Matthys, C., Himpens, J. M., Focquet, M. A. M. R. M., Ramos, A., Nato, M. G., Vidal, T., Andalib, A., Siblini, A., Ferri, L., Abdarabo, L., Nevo, Y., Pescarus, R., Yang, W., Hamed, H., Liagre, A., Bergeat, D., Marie, D. M., Martini, F., Regis, F., Genser, L., Skalli, M., Nedelcu, M., Smejkal, M., Kassir, R., Nicolas, R., Stier, C., Nedelcut, D. -S., Christodoulidis, G., Vennapusa, A., Kermansaravi, M., Raziel, A., Sakran, N., Oldani, A., Boru, C. E., Mecheri, F., Ciccarese, F., Cesana, G. C., Musella, M., Uccelli, M., Foletto, M., Auricchio, P., Olmi, S., Seki, Y., Kasteleijn, A., Van 'T Hof, G., Apers, J. A., Hart, J. W. H., Van De Sande, J. S. L., Takkenberg, M., Feskens, P. B. G. M., Snoekx, R., Plat, V. D., Sandvik, J., Kalinowski, P., Nabais, C., Al-Bahrani, A. Z., Al Zoubi, M., Bettonica, C., Osorio, J., Tejedor-Tejada, J., Sanz, L. M., Cuadrado, M., Moorjani, R. G., Yannick, F., Suter, M., Borbely, Y., Joerg, Z., Barajas-Gamboa, J. S., Kroh, M., Kisiel, A. P., Kamocka, A., Immanuel, A., Sgromo, B., Gopinath, B., Khoo, D., Mukherjee, S., Pournaras, D., Underwood, T., Griffiths, E. A., Miller, G. V., Jaretzke, H., Dmitrewski, J., Wadley, M. S., Al-Housni, R., Gillies, R. S., Singhal, R., Preston, S. R., Robinson, S. J., Hawkins, W. J., Adamo, M., El Kalaawy, M., Gossage, J., Crawford, C. B., Jaruvongvanich, V., Surgery, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, and Plastic, Reconstructive and Hand Surgery

Subjects
Adult, obesity, Sleeve gastrectomy, medicine.medical_specialty, Palliative treatment, bariatric surgery, esophageal cancer, esophagogastric cancer, gtastric cancer, metabolic surgery, adult, female, gastrectomy, humans, middle aged, retrospective studies, treatment outcome, gastric bypass, morbid, stomach neoplasms, medicine.medical_treatment, Esophageal cancer, Esophagogastric cancer, Population, Gastric Bypass, Bariatric Surgery, Gastrectomy, Stomach Neoplasms, medicine, Humans, In patient, Adjustable gastric band, education, Retrospective Studies, Bariatric surgery, education.field_of_study, business.industry, Cancer, Middle Aged, medicine.disease, Obesity, Obesity, Morbid, Surgery, Treatment Outcome, Adenocarcinoma, Female, Metabolic surgery, Gastric cancer, business
Abstract

Background Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Oesophago-Gastric (OG) malignancies in patients who have had a prior bariatric procedure have not been fully characterised. Objective To characterise OG malignancies after bariatric procedures. Setting University Hospital, United Kingdom. Methods We performed a retrospective, multi-centre observational study of patients with OG malignancies after bariatric surgery to characterise this condition. Results This study includes 170 patients from 75 centres in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years and the mean weight 128.8 ± 28.9 kg. Females comprised 57.3% (n=98) of the population. Most (n=64) patients underwent a Roux-en-Y Gastric Bypass (RYGB) followed by Adjustable Gastric Band (AGB) (n = 46) and Sleeve Gastrectomy (SG) (n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One-third of patients presented with metastatic disease. The majority of tumours were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under one year for most patients who died over the intervening period. Conclusions The OGMOS (Oesophago-Gastric Malignancies after Obesity/ Bariatric Surgery) study presents the largest series to date of patients developing OG malignancies after bariatric surgery and attempts to characterise this condition.

Published
2022

54. Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer : a modified Delphi consensus process

Author

Swathikan Chidambaram, Nikhil M Patel, Viknesh Sounderajah, Rita Alfieri, Luigi Bonavina, Edward Cheong, Andy Cockbain, Xavier Benoit D’Journo, Lorenzo Ferri, Ewen A Griffiths, Peter Grimminger, Caroline Gronnier, Christian Gutschow, Jakob Hedberg, Joonas H Kauppila, Sjoerd Lagarde, Donald Low, Philippe Nafteux, Grard Nieuwenhuijzen, Magnus Nilsson, Riccardo Rosati, Wolfgang Schroeder, B Mark Smithers, Mark I van Berge Henegouwen, Richard van Hillegesberg, David I Watson, Ravinder Vohra, Nick Maynard, Sheraz R Markar, Surgery, CCA - Imaging and biomarkers, Amsterdam Gastroenterology Endocrinology Metabolism, Chidambaram, Swathikan, Patel, Nikhil M, Sounderajah, Viknesh, Alfieri, Rita, Bonavina, Luigi, Cheong, Edward, Cockbain, Andy, D'Journo, Xavier Benoit, Ferri, Lorenzo, Griffiths, Ewen A, Grimminger, Peter, Gronnier, Caroline, Gutschow, Christian, Hedberg, Jakob, Kauppila, Joonas H, Lagarde, Sjoerd, Low, Donald, Nafteux, Philippe, Nieuwenhuijzen, Grard, Nilsson, Magnu, Rosati, Riccardo, Schroeder, Wolfgang, Smithers, B Mark, van Berge Henegouwen, Mark I, van Hillegesberg, Richard, Watson, David I, Vohra, Ravinder, Maynard, Nick, and Markar, Sheraz R

Subjects
Cancer och onkologi, endoscopic, SDG 3 - Good Health and Well-being, gastric cancer, Kirurgi, Cancer and Oncology, Gastroenterology, surveillance, Surgery, General Medicine, esophageal cancer, symptom
Abstract

BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value. ispartof: DISEASES OF THE ESOPHAGUS vol:36 issue:1 ispartof: location:United States status: published

Published
2023

55. Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions

Author

Sander Ubels, Merel Lubbers, Moniek H P Verstegen, Stefan A W Bouwense, Elke van Daele, Lorenzo Ferri, Suzanne S Gisbertz, Ewen A Griffiths, Peter Grimminger, George Hanna, Michal Hubka, Simon Law, Donald Low, Misha Luyer, Robert E Merritt, Christopher Morse, Carmen L Mueller, Grard A P Nieuwenhuijzen, Magnus Nilsson, John V Reynolds, Ulysses Ribeiro, Riccardo Rosati, Yaxing Shen, Bas P L Wijnhoven, Bastiaan R Klarenbeek, Frans van Workum, Camiel Rosman, Surgery, CCA - Cancer Treatment and Quality of Life, CCA - Cancer Treatment and quality of life, MUMC+: MA Heelkunde (9), RS: FHML non-thematic output, Ubels, Sander, Lubbers, Merel, Verstegen, Moniek H P, Bouwense, Stefan A W, van Daele, Elke, Ferri, Lorenzo, Gisbertz, Suzanne S, Griffiths, Ewen A, Grimminger, Peter, Hanna, George, Hubka, Michal, Law, Simon, Low, Donald, Luyer, Misha, Merritt, Robert E, Morse, Christopher, Mueller, Carmen L, Nieuwenhuijzen, Grard A P, Nilsson, Magnu, Reynolds, John V, Ribeiro, Ulysse, Rosati, Riccardo, Shen, Yaxing, Wijnhoven, Bas P L, Klarenbeek, Bastiaan R, van Workum, Fran, and Rosman, Camiel

Subjects
COMPLICATIONS, Esophageal Cancer, SURGERY, Gastroenterology, Anastomotic Leak, ENHANCE, General Medicine, MIXED METHODS, Esophagectomy, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Focus Group, MANAGEMENT, QUALITY, RATES, Survey, INTEGRATION
Abstract

Contains fulltext : 288475.pdf (Publisher’s version ) (Open Access) Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.

Published
2022

56. OGC O06 An international cohort study of prognosis associated with pathologically complete response following neoadjuvant chemotherapy vs. chemoradiotherapy of surgical treated esophageal adenocarcinoma

Author

Sheraz Markar, Jonathan Cools-Lartigue, Carmen Mueller, Wayne Hofstetter, Magnus Nilsson, Ilka Ilonen, Henna Soderstrom, Jari Rasanen, Suzanne Gisbertz, George Hanna, Jessie Elliott, John Reynolds, Aaron Kisiel, Ewen Griffiths, Mark van Berge Henegouwen, and Lorenzo Ferri

Subjects
Surgery
Abstract

Background Objective: To compare overall (OS) and recurrence-free survival (RFS) in esophageal adenocarcinoma patients with a complete pathological response (pCR) following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). Background In the absence of survival differences in several prior studies comparing nCT with nCRT, the higher rate of pCR after nCRT has been suggested as reason to prefer this modality over nCT. Methods An international cohort study included data from 8 high-volume centers. Inclusion criteria was patients with esophageal adenocarcinoma, between 2008 and 2018, who had a pCR following nCT or nCRT. Univariate analysis was used to compare demographic factors, and Kaplan-Meier survival analysis used to compare 5-year OS and RFS between groups. Results 465 patients with pCR following neoadjuvant treatment were included; 132 received nCT and 333 received nCRT. There was no statistically significant difference in 5-year OS between groups (78.8% (nCT) vs. 65.5% (nCRT), p=0.099), with a similar result demonstrated in multivariate analysis (HR=1.19, 95%CI 0.77 to 1.84). 5-year RFS was significantly reduced in patients with a pCR following neoadjuvant chemoradiotherapy (75.3% (nCRT) vs. 87.1% (nCT), p=0.026). Multivariate analysis confirmed nCRT was associated with a poorer 5-year RFS (HR=1.70, 95%CI 1.22 to 2.99). nCRT associated with a significantly greater prevalence of 5-year distant recurrence (Odds ratio = 2.50, 95%CI 1.25–4.99). Conclusions The results of this international cohort study show that the prognosis of pCR following different neoadjuvant regimes differs, bringing into question the validity of this measure as an oncological surrogate when comparing neoadjuvant treatment schemes for esophageal adenocarcinoma.

Published
2022

57. Data-Independent Acquisition and Quantification of Extracellular Matrix from Human Lung in Chronic Inflammation-Associated Carcinomas

Author

Joanna Bons, Deng Pan, Samah Shah, Rosemary Bai, Chira Chen‐Tanyolac, Xianhong Wang, Daffolyn R. Fels Elliott, Anatoly Urisman, Amy O'Broin, Nathan Basisty, Jacob Rose, Veena Sangwan, Sophie Camilleri‐Broët, James Tankel, Philippe Gascard, Lorenzo Ferri, Thea D. Tlsty, and Birgit Schilling

Subjects
Inflammation, Proteomics, Extracellular Matrix Proteins, Biochemistry & Molecular Biology, extracellular matrix, Carcinoma, serpins, Lung Cancer, Biological Sciences, Medical and Health Sciences, Biochemistry, quantification, Rare Diseases, Squamous Cell, Clinical Research, Information and Computing Sciences, data-independent acquisition, lung squamous cell carcinoma, Humans, 2.1 Biological and endogenous factors, Aetiology, Molecular Biology, Lung, Biotechnology, Cancer
Abstract

Early events associated with chronic inflammation and cancer involve significant remodeling of the extracellular matrix (ECM), which greatly affects its composition and functional properties. Using lung squamous cell carcinoma (LSCC), a chronic inflammation-associated cancer (CIAC), we optimized a robust proteomic pipeline to discover potential biomarker signatures and protein changes specifically in the stroma. We combined ECM enrichment from fresh human tissues, data-independent acquisition strategies, and stringent statistical processing to analyze ‘Tumor’ and matched adjacent histologically normal (‘Matched Normal’) tissues from patients with LSCC. Overall, 1,802 protein groups were quantified with at least two unique peptides, and 56% of those proteins were annotated as ‘extracellular’. Confirming dramatic ECM remodeling during CIAC progression, 529 proteins were significantly altered in the ‘Tumor’ compared to ‘Matched Normal’ tissues. The signature was typified by a coordinated loss of basement membrane proteins and small leucine-rich proteins. The dramatic increase in the stromal levels of SERPINH1/heat shock protein 47, that was discovered using our ECM proteomic pipeline, was validated by immunohistochemistry (IHC) of ‘Tumor’ and ‘Matched Normal’ tissues, obtained from an independent cohort of LSCC patients. This integrated workflow provided novel insights into ECM remodeling during CIAC progression, and identified potential biomarker signatures and future therapeutic targets.Statement of significance of the studyThe extracellular matrix (ECM) is a complex scaffolding network composed of glycoproteins, proteoglycans and collagens, which binds soluble factors and, most importantly, significantly impacts cell fate and function. Alterations of ECM homeostasis create a microenvironment promoting tumor formation and progression, therefore deciphering molecular details of aberrant ECM remodeling is essential. Here, we present a multi-laboratory and refined proteomic workflow, featuring i) the prospective collection of tumor and matched histologically normal tissues from patients with lung squamous cell carcinoma, ii) the enrichment for ECM proteins, and iii) subsequent label-free data-independent acquisition (DIA)-based quantification. DIA is a powerful strategy to comprehensively profile and quantify all detectable precursor ions contained in the biological samples, with high quantification accuracy and reproducibility. When combined with very stringent statistical cutoffs, this unbiased strategy succeeded in capturing robust and highly confident proteins changes associated with cancer, despite biological variability between individuals. This label-free quantification workflow provided the flexibility required for ongoing prospective studies. Discussions with clinicians, surgeons, pathologists, and cancer biologists represent an opportunity to interrogate the DIA digitalized maps of the samples for newly formulated questions and hypotheses, thus gaining insights into the continuum of the disease and opening the path to novel ECM-targeted therapies.

Published
2022

58. CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma: A Propensity-Matched Comparison

Author

Noel E. Donlon, Brendan Moran, Anitha Kamilli, Maria Davern, Andrew Sheppard, Sinead King, Claire L. Donohoe, Maeve Lowery, Moya Cunningham, Narayanasamy Ravi, Carmen Mueller, Jonathan Cools-Lartigue, Lorenzo Ferri, and John V. Reynolds

Subjects
Male, Carbon Monoxide, Sarcopenia, Esophageal Neoplasms, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Surgery, Female, Esophagogastric Junction, Adenocarcinoma, Respiratory Insufficiency, Neoadjuvant Therapy
Abstract

The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier.A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS ( P0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS ( P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively ( P =0.03). In-hospital mortality, respectively, was 1% versus 2% ( P =0.9), and Clavien DindoIII 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42).Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.

Published
2022

59. Development of the ParaOesophageal hernia SympTom (POST) tool

Author

Aiysha, Puri, Nikhil M, Patel, Viknesh, Sounderajah, Lorenzo, Ferri, Ewen A, Griffiths, Donald, Low, Nick, Maynard, Carmen, Mueller, Manuel, Pera, Mark I, van Berge Henegouwen, David I, Watson, Giovanni, Zaninotto, George B, Hanna, Sheraz R, Markar, S, Thompson, Surgery, Puri, Aiysha, Patel, Nikhil M, Sounderajah, Viknesh, Ferri, Lorenzo, Griffiths, Ewen A, Low, Donald, Maynard, Nick, Mueller, Carmen, Pera, Manuel, van Berge Henegouwen, Mark I, Watson, David I, Zaninotto, Giovanni, Hanna, George B, Markar, Sheraz R, Rosati, Riccardo, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Consensus, Hernia, Hiatal, Delphi Technique, Surveys and Questionnaires, Humans, Surgery
Abstract

Background The aim of this study was to develop a symptom severity instrument (ParaOesophageal hernia SympTom (POST) tool) specific to para-oesophageal hernia (POH). Methods The POST tool was developed in four stages. The first was establishment of a Steering Committee. In the second stage, items were generated through a systematic review and online scoping survey of international experts. In the third stage, a three-round modified Delphi consensus process was conducted with a group of international experts who were asked to rate the importance of candidate items. An a priori threshold for inclusion was set at 80 per cent. The modified Delphi process culminated in a consensus meeting to develop the first iteration of the tool. In the final stage, two international patient workshops were held to assess the content validity and acceptability of the POST tool. Results The systematic review and scoping survey generated 64 symptoms, refined to 20 for inclusion in the modified Delphi consensus process. Twenty-six global experts participated in the Delphi consensus process. Five symptoms reached consensus across two rounds: difficulty getting solid foods down, chest pain after meals, difficulty getting liquids down, shortness of breath only after meals, and an early feeling of fullness after eating. The subsequent patient workshops deemed these five symptoms to be relevant and suggested that reflux should be included; these were taken forward to create the final POST tool. Conclusion The POST tool is the first instrument designed to capture POH-specific symptoms. It will allow clinicians to standardize reporting of symptoms of POH and evaluate the response to surgical intervention.

Published
2022

60. Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture

Author

Andreas Schulze-Bonhage, Patrick May, Samuel Berkovic, Lorenzo Ferri, Monica Gagliardi, Adam Strzelczyk, Oluyomi Modupe Adesoji, Vytautas Kasiulevicius, Heidi Kirsch, Algirdas Utkus, Bobby Koeleman, and Gianpiero Cavalleri

Abstract

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here, we report a trans-ethnic GWAS including 29,944 cases, stratified into three broad- and seven sub-types of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants substantially close the missing heritability gap for GGE. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analysis of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current anti-seizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.

Published
2022

62. Epilepsy in MT‐ATP6 ‐ related mils/NARP: correlation of elettroclinical features with heteroplasmy

Author

Leonardo Caporali, Lara Alvisi, Daniela Fulitano, Barbara Mostacci, Raffaella Minardi, Valerio Carelli, Chiara La Morgia, Patrizia Avoni, Lorenzo Ferri, Rocco Liguori, Paolo Tinuper, Corrado Zenesini, Francesca Bisulli, Maria Lucia Valentino, Lidia Di Vito, Laura Licchetta, Licchetta L., Ferri L., La Morgia C., Zenesini C., Caporali L., Lucia Valentino M., Minardi R., Fulitano D., Di Vito L., Mostacci B., Alvisi L., Avoni P., Liguori R., Tinuper P., Bisulli F., and Carelli V.

Subjects
0301 basic medicine, Male, Electroencephalography, medicine.disease_cause, progressive myoclonic epilepsy (PME), Severity of Illness Index, Epilepsy, 0302 clinical medicine, maternally inherited Leigh's syndrome (MILS), Mutation, medicine.diagnostic_test, biology, General Neuroscience, Mitochondrial Myopathies, Middle Aged, Mitochondrial Proton-Translocating ATPases, MT-ATP6 MT-ATP6, Heteroplasmy, Pedigree, Child, Preschool, MT-ATP6, Female, medicine.symptom, Leigh Disease, Brief Communications, Retinitis Pigmentosa, RC321-571, Adult, medicine.medical_specialty, Ataxia, Neurosciences. Biological psychiatry. Neuropsychiatry, Brief Communication, MT‐ATP6 MT‐ATP6, 03 medical and health sciences, Internal medicine, Retinitis pigmentosa, medicine, Humans, RC346-429, neuropathy, ataxia, retinitis pigmentosa (NARP), business.industry, medicine.disease, Brain Waves, 030104 developmental biology, Endocrinology, biology.protein, epilepsy, Neurology (clinical), Neurology. Diseases of the nervous system, business, Asymptomatic carrier, 030217 neurology & neurosurgery
Abstract

The study aims to characterize the epilepsy phenotype of maternally inherited Leigh's syndrome (MILS) and neuropathy, ataxia, retinitis pigmentosa (NARP) due to mutations in the mitochondrial ATP6 gene and to correlate electroclinical features with mutant heteroplasmy load (HL). We investigated 17 individuals with different phenotype, from asymptomatic carriers to MILS: 11 carried the m.8993T>G mutation, 5 the m.8993T>C and one the novel, de novo m.8858G>A mutation. Seizures occurred in 37.5% of patients, EEG abnormalities in 73%. We ranked clinical and EEG abnormalities severity and performed quantitative EEG to estimate Abnormality Ratio (AR) and Spectral Relative Power (SRP). Spearman’s rho and Kruskal–Wallis test were used for correlation with heteroplasmy load (HL). HL correlated with disease severity (Rho=0.63, P=0.012) and was significantly higher in patients with seizures or EEG abnormalities (P=0.014). HL correlated with EEG severity score only for the m.8993T>G (Rho=0.73, P=0.040), showing a trend toward a positive correlation with AR and delta SPR, irrespective of the mutation.

Published
2021

63. Abstract 5959: Dissecting the stromal drivers of gastroesophageal adenocarcinoma chemoresistance

Author

Kulsum Tai, Sanjima Pal, Julie Bérubé, Iris Kong, Adam Hoffman, Swneke Bailey, Aki Kirbizakis, Sui Huang, Michael Strasser, David Gibbs, Nicholas Bertos, Veena Sangwan, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

Gastroesophageal adenocarcinoma (GEA) is the fastest rising cancer in North America. Over the course of five years, the survival rate is 200 GEA patients. A single-cell RNA sequencing atlas developed from >30 GEA DCF- or FLOT-treated patient samples will be used to identify CAF markers and targetable processes. CAF sub-populations will then be elucidated and correlated to tumor response. IF, FACS, and ELISA will be performed for subsequent CAF marker validation and characterization. Ex vivo drug testing with DCF or FLOT will be conducted on PDO-CAF co-cultures to recapitulate their drug response. Citation Format: Kulsum Tai, Sanjima Pal, Julie Bérubé, Iris Kong, Adam Hoffman, Swneke Bailey, Aki Kirbizakis, Sui Huang, Michael Strasser, David Gibbs, Nicholas Bertos, Veena Sangwan, Lorenzo Ferri. Dissecting the stromal drivers of gastroesophageal adenocarcinoma chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5959.

Published
2023

64. Abstract 1315: NETs act as immunosuppressive agents within lymph nodes during cancer

Author

Ariane Brassard, Xin Su, Iqraa Dhoparee-Doomah, Sabrina Leo, Lixuan Feng, France Bourdeau, Betty Giannias, Corissa Larson, Qian Qiu, Jonathan Spicer, Lorenzo Ferri, and Jonathan Cools-Lartigue

Subjects
Cancer Research, Oncology
Abstract

Metastasis is responsible for 90% of all cancer-related deaths, making it the most significant challenge in cancer treatment for clinicians worldwide. Metastasis is thought to occur in a stepwise process, in which local lymph nodes (LNs) are first colonized by tumour cells before proceeding to distal organs. However, the mechanism by which LN metastasis facilitates distal metastasis is poorly understood. LNs undergo environmental changes to accommodate tumour cell growth within, notably by shifting the environment towards immunosuppression to shut down anti-tumour immune cells. This immunosuppressive environment is critical for the establishment of LN metastases, as cytotoxic CD8 T cells will otherwise neutralize incoming circulating tumour cells. Neutrophils are among the first cells recruited to tumour-draining LNs to mediate the environmental shift, and yet their method of action has not been fully elucidated. They have recently been found to secrete NETs within LNs during cancer, which are pro-inflammatory web-like formations of DNA decorated with antimicrobial peptides. While NETs have been shown to exert pro-tumour effects in the tumour microenvironment and to facilitate metastasis as a whole, their role in LNs has never been explored. Using a NETs deficient mouse model (PAD4-/-), we report that NETs deposition within the tumour-draining LNs of mice upregulates the Treg population while simultaneously downregulating anti-tumour CD8 T cell proliferation and activation. Following these findings, we performed an in vitro suppression assay and found that NETs-educated Tregs hinder the expansion of CD8 T cells more than non-NETs-educated Tregs. Finally, through an induced metastasis mouse model, we have observed that tumour-draining LN resection as well as the absence of NETs protects against the development of distal metastasis, and decreases body-wide inflammation as seen by a lowered Neutrophil-to-Lymphocyte ratio in the circulation. Taken together, these findings highlight the role of NETs deposition in LNs as a key player in disease progression and bring forward a potential target for anti-metastatic drug development. Citation Format: Ariane Brassard, Xin Su, Iqraa Dhoparee-Doomah, Sabrina Leo, Lixuan Feng, France Bourdeau, Betty Giannias, Corissa Larson, Qian Qiu, Jonathan Spicer, Lorenzo Ferri, Jonathan Cools-Lartigue. NETs act as immunosuppressive agents within lymph nodes during cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1315.

Published
2023

65. Abstract 168: Esophageal adenocarcinoma-on-a-chip; modeling patient specific disease progression and a step towards functional precision oncology

Author

Sanjima Pal, Elee Shimshoni, Salvador Flores-Torres, Julie Bérubé, Kulsum Tai, Iris Kong, Betty Giannias, Sean Hall, Nicholas Bertos, Veena Sangwan, Donald E. Ingber, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

Introduction: Esophageal cancer causes sixth most cancer-related morbidity and mortality worldwide, with a survival rate of 60%) in North America. Systemic docetaxel-based triplet chemotherapy represents the best standard of care, approx. 60% of patients showcasing innate chemo-resistance or developing acquired chemo-resistance. 3D organoids provide a robust and heterogeneous cell source but lack the stromal microenvironment. We established a high-fidelity, stromal-inclusive tumor-on-chip platform expanding on tumor heterogeneity with micro-physiological relevance and flexible complexity. Methods: A total of 8 (4 chemo-sensitive and 4 chemo-resistant) treatment naïve patient-derived organoids (PDOs) and matched fibroblasts were selected to develop syngeneic human esophageal microtissues (tumor and adjacent) on commercially available (Emulate), compartmentalized, porous polydimethylsiloxane (PDMS) membrane-based microfluidic device. Chips accommodate organoids-derived epithelial cells at the upper mucosal channel and matched fibroblasts at the bottom stromal channel. 3D-microtissue development on the chip and treatment-induced cytotoxicity were examined for up to 11 days. We followed the FLOT (docetaxel, oxaliplatin, and 5-fluorouracil; 1:1.7:52) based chemotherapy regime on the chip and evaluated the recapitulation of patient-specific response. Epithelial barrier integrity, adenocarcinoma-associated cellular proteins, and level of cyfra 21-1 (circulating tumor biomarker) were determined on-chip grown microtissues. Results: Real-time brightfield microscopic observations revealed that the EA chips manifest mucin production, adequate tissue tight epithelial barriers, and distinct morphological characteristics that emerged with adenocarcinoma progression. Presence of pleomorphic cells (multiple shapes and sizes), establishment of tight epithelial barriers and formation of mature microvilli was observed via electron microscopy. Patient specific tumor tissue growth were observed for maximum 12 days under a physiologically relevant media flow. Perfusion of pharmacokinetically pertinent doses of triplet chemotherapeutic compounds performed through the stromal channel and each chip recapitulated level of chemosensitivity observed in the patient. Fluorescent probes and LDH assay also demonstrated patient-specific chemo response. Confocal imaging revealed differential expression of proliferation (ki67), epithelial (CK7, E-cadherin), and mesenchymal (Vimentin) markers in each patient-derived chip. Conclusions: Human esophageal adenocarcinoma-on-a-chip is a novel, most human-relevant biomimetic platform built on a microfluidic chip and a potential alternative to inadequate pre-clinical animal models in the future. Citation Format: Sanjima Pal, Elee Shimshoni, Salvador Flores-Torres, Julie Bérubé, Kulsum Tai, Iris Kong, Betty Giannias, Sean Hall, Nicholas Bertos, Veena Sangwan, Donald E. Ingber, Lorenzo Ferri. Esophageal adenocarcinoma-on-a-chip; modeling patient specific disease progression and a step towards functional precision oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 168.

Published
2023

66. Treatment selection and outcomes of locally advanced esophageal cancer in octo- and nonagenarians: Is a curative intent multimodal approach feasible?

Author

Nabeel Ahmed, James Tankel, Jamil Asselah, Thierry Alcindor, Joanne Alfieri, Marc David, Sara Najmeh, Jonathan Cools-Lartigue, Jonathan Spicer, Carmen L. Mueller, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

333 Background: Neoadjuvant therapy followed by en bloc surgical resection affords the highest rates of survival from locally advanced esophageal cancer (LAEC) and represents the standard of care. However, patients of advanced age may not be offered this approach due to concerns over toxicity/tolerability. The outcomes of different treatment modalities for patients aged 80 and above with LAEC are not well described. Methods: A retrospective, single center, cohort analysis was performed on a prospectively maintained comprehensive esophageal cancer database. Between 2010-20, all patients ≥80yrs with locally advanced esophageal/GEJ cancer (cT2-4a, Nany, M0) were identified and outcomes stratified according to the following treatment categories: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by surgery; definitive CRT (dCRT); upfront surgery; palliative CT or RT; or best supportive care (BSC). Data presented as median(range). Univariate analysis used for clinicopathological data (*p

Published
2023

67. Docetaxel-based triplet neoadjuvant therapy for esophageal adenocarcinoma: A comprehensive analysis of outcomes spanning over a decade

Author

James Tankel, Nabeel Ahmed, Thierry Alcindor, Jamil Asselah, Petr Kavan, Frederic Lemay, Dominique A. Frechette, Shelly Sud, Lawrence Lee, Sara Najmeh, Jonathan Spicer, Jonathan Cools-Lartigue, Carmen L. Mueller, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

332 Background: Docetaxel-based therapy is currently the most effective neoadjuvant regimen for locally advanced gastroesophageal adenocarcinoma. However, prior trials were primarily designed to target gastric cancer. As survival associated with taxane-based chemotherapy in esophageal adenocarcinoma (EAC) is less well described, we sought to review our experience with docetaxel based therapy as a neoadjuvant approach for EAC. Methods: A single centre retrospective review of a prospectively maintained upper GI cancer surgical database was performed (2008-2021). Patients with EAC undergoing curative intent neoadjuvant therapy with two similar docetaxel-based regimens (DCF - Docetaxel/Cisplatin/5FU or FLOT - 5FU, Leucovorin, Oxaliplatin, and Docetaxel) followed by en-bloc resection were included. Gastric/EGJ type III tumors were excluded. Clinicopathological data and overall survival (OS) were recorded and stratified by chemotherapy type (DCF vs FLOT). Data are presented as median (+/-SD). Mann-Whitney U tests for continuous or Fischer exact test for categorical variables determined significance. Kaplan-Meier curves compared OS. Results: 225 EAC patients were identified: Age 64.2 (±10.3) and tumor location was Esophageal/EGJ I/EGJ II (106/33/86). Clinical stage was cT3-4 in 201/225 (89.3%) and most were cN+ (200/225: 88.9%). There were 121 (53.7%) treated with neoadjuvant DCF whilst 104 (46.3%) received FLOT. All pre-op cycles were completed in 181 (80.4%) and did not differ between DCF and FLOT (81.8% vs 78.8% - NS). Operative procedure included Ivor Lewis in 188 (83.5%), left thoraco-abdominal esophagectomy in 20 (8.8%), and McKeown in 17 (7.5%) and also did not differ between DCF and FLOT. In terms of pathologic outcomes, the median lymph node yield was 35 (±16) of which 3.6±5.8 were positive). There was no difference when comparing between regimens. There were 134 (59.6%) patients ypN1-3 (DCF=76(62.8%) vs FLOT=58(55.8%)- NS). An R0 resection was achieved in 210 (93%) patients (DCF=92.6% vs FLOT=94.2%- NS). Complete pathological response (no residual cancer) was found in 21 patients (9.3%) (DCF=14(11.6%) vs FLOT=7(6.7%) – NS). At follow up of 41(±36) months (DCF= 52±41 vs FLOT=27±23 - p

Published
2023

68. Disorder of sex development associated with a novel homozygous nonsense mutation in <scp> COG6 </scp> expands the phenotypic spectrum of <scp>COG6‐CDG</scp>

Author

Lorenzo Iughetti, Maria Carolina Bariola, Umberto Cattini, Laura Lucaccioni, Lorenzo Ferri, Emma Bertucci, Francesco Torcetta, Licia Lugli, Alberto Berardi, and Amelia Morrone

Subjects
0301 basic medicine, Genetics, congenital, hereditary, and neonatal diseases and abnormalities, Microcephaly, Glycosylation, Conserved oligomeric Golgi complex, Nonsense mutation, 030105 genetics & heredity, Gene mutation, Biology, medicine.disease, Abnormal protein glycosylation, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Cog, congenital disorders of glycosylation, conserved oligomeric Golgi complex, disorder of sexual differentiation, chemistry, medicine, Genitalia morphogenesis, Genetics (clinical)
Abstract

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.

Published
2021

69. Change in Density Not Size of Esophageal Adenocarcinoma During Neoadjuvant Chemotherapy Is Associated with Improved Survival Outcomes

Author

James Tankel, Henna Söderström, Edouard Reizine, Giovanni Artho, Alexander Calderone, Carmen Mueller, Sara Najmeh, Jonathan Spicer, Lorenzo Ferri, and Jonathan Cools-Lartigue

Subjects
Esophagectomy, Cohort Studies, Esophageal Neoplasms, Gastroenterology, Humans, Surgery, Adenocarcinoma, Neoadjuvant Therapy, Retrospective Studies, Neoplasm Staging
Abstract

Changes in the size and density of esophageal malignancy during neoadjuvant chemotherapy (NCT) may be useful in predicting overall survival (OS). The aim of this study was to explore this relationship in patients with adenocarcinoma.A retrospective single-centre cohort study was performed. Consecutive patients with esophageal adenocarcinoma who received NCT followed by en bloc resection with curative intent were identified. Pre- and post-NCT computed tomography scans were reviewed. The percentage difference between the greatest tumor diameter, esophageal wall thickness and tumor density was calculated. Multivariate Cox regression analysis identified variables independently associated with OS. A ROC analysis was performed on radiological markers to identify optimal cut-off points with Kaplan-Meier plots subsequently created.Of the 167 identified, 88 (51.5%) had disease of the gastro-esophageal junction and 149 (89.2%) were clinical T3. In total, 122 (73.1%) had node-positive disease. Increased tumor density (HR 1.01 per % change, 95% CI 1.00-1.02, p = 0.007), lymphovascular invasion (HR 3.23, 95% CI 1.34-7.52, p = 0.006) and perineural invasion (HR 2.51, 95% CI 1.03-6.08, p = 0.048) were independently associated with a decrease in OS. Patients who had a decrease in their tumor density during the time they received NCT of ≥ 20% in Hounsfield units had significantly longer OS than those who did not (75.5 months versus 34.4 months, 95% CI 38.83-105.13/18.63-35.07, p = 0.025).Interval changes in the density, not size, of esophageal adenocarcinoma during the time that NCT are independently associated with OS.

Published
2022

70. Long-Term Quality of Life After Esophagectomy for Esophageal Cancer

Author

Amit Katz, Yehonatan Nevo, José Luis Ramírez García Luna, Sonia Anchouche, James Tankel, Natasha Caminsky, Carmen Mueller, Jonathan Spicer, Jonathan Cools-Lartigue, and Lorenzo Ferri

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract

Surgery, as part of a multimodal approach, offers the greatest chance of cure for esophageal cancer. However, esophagectomy is often perceived as having a lasting impact on quality of life (QOL), biasing some physicians and patients toward nonoperative management. A comprehensive understanding of the dynamic changes in patient-centered outcomes is therefore important for decision making. Our objective was to determine the long-term QOL after esophagectomy.Data were obtained from a prospectively collected (2006-2015) esophagectomy database at a high-volume center, and patients surviving 3 or more years were identified. Health-related QOL was evaluated using the Functional Assessment of Cancer Therapy-Esophageal Module (FACT-E) at diagnosis and every 3 to 6 months, and was stratified according to operative approach, stage, and complications. In addition, QOL scores were compared with normative population values.Of 480 patients, 47% (n = 226) survived 3 or more years and 70% (158 of 226) completed the health-related QOL assessments. Time of follow-up was 5.1 ± 2.8 years. After a reduction at 1 to 3 months, FACT-E increased from a baseline of 126 (95% CI, 121-131) to 133 (95% CI, 127-139) at 12 months, and to 147 (95% CI, 142-153) by 5 years. There was no difference in long-term FACT-E with respect to the surgical approach, clinical and pathologic stage, or postoperative complications. At long-term follow-up (more than 3 years), QOL did not differ significantly from the normative population reference values.The long-term QOL of esophagectomy patients surviving at least 3 years is improved when compared with the time of diagnosis and does not differ from the general population.

Published
2022

71. The Role of Palliative Surgery in Stage IV Gastric Cancer: A Retrospective Study

Author

Yehonatan Nevo, Dominique Morency, Anitha Kammili, Lina Abdrabo, Kyle Zullo, Saleh Almatar, Jonathan Cools-Lartigue, Lorenzo Ferri, and Carmen Mueller

Subjects
Gastrectomy, Stomach Neoplasms, Palliative Care, Humans, General Medicine, Adenocarcinoma, Retrospective Studies
Abstract

Background: Palliative chemotherapy is the mainstay of treatment for metastatic gastric adenocarcinoma but in some patients, surgically correctable factors such as obstruction lead to intolerance of further systemic treatment. The aim of this study was to evaluate the role of selective palliative surgery in incurable gastric cancer. Methods: All patients with stage IV and locally advanced unresectable gastric adenocarcinoma treated at a single centre from March 2006 to January 2019 were included. Data were retrieved from a prospectively maintained database. Patients were categorized into palliative surgery (PS) and no surgery (NS). Results: Of 666 patients with gastric cancer treated over the study period, 146 patients had stage IV gastric adenocarcinoma and 121 patients met inclusion criteria. Sites of metastases were peritoneum (55; 46%), non-regional lymph nodes (10; 8%), solid organ (17, 14%), adjacent organ invasion (4, 3.3%) and a combination of factors (32, 26%). Forty-six (38%) patients underwent palliative surgery which included anatomical gastrectomy (total, subtotal, distal or proximal, 78%) gastro-jejunal bypass and feeding jejunostomy (12%). Thirty-day post-operative complications occurred in 24 patients (52%) with one mortality (2.1%). Following surgery, 52% received systemic chemotherapy. For the PS and NS groups respectively, median overall survival was 9.1 versus 9.4 months ( p = 0.6) and median progression-free survival was 7.1 versus 6.7 months ( p = 0.2) after a follow up period of 7.3 (4.7-13.1) versus 7.8 (2.6-13.4) months ( p = 0.46). Conclusion: Targeted surgical intervention for incurable gastric cancer can be used to palliate symptoms and facilitate continuation of systemic therapy with acceptable risks and post-operative outcomes.

Published
2022

72. Derived Dentin Graft as Autologous Bone Regeneration in Implant Surgery: A Histological and Radiographic Investigation

Author

Carini, F, Ferri, L, Coppola, G, Monai, D, Fabrizio Carini, Lorenzo Ferri, Giulia Coppola, Fabio Carini, Dario Monai, Carini, F, Ferri, L, Coppola, G, Monai, D, Fabrizio Carini, Lorenzo Ferri, Giulia Coppola, Fabio Carini, and Dario Monai

Abstract

Background: This study has been conducted to evaluate the dentin regeneration potential as an autologous graft material for the preservation of the bone volume in the post-extraction socket. Tooth Transformer has been used as the device required to demineralize the dentin got from the extracted elements, which led to obtaining a granular material rich in collagen and growth factors. Methods: All 8 patients selected for the study underwent two surgical procedures. During the first surgery, the affected elements have been extracted, the Tooth Transformer protocol has been run, and the material has been grafted into the existing bone defects and post-extraction socket. After three months, the biopsy of the regenerated areas has been performed and the implants required for prosthetic rehabilitation were placed in the same site. For two of the 8 patients, the implant has been placed with the support of a surgical guide. Result: CBCT and histological analysis’ results after 3 months confirmed the actual replacement of grafted material and the regeneration of bone tissue suitable for implant rehabilitation. Conclusion: Thus, the Tooth Transformer proves to be an effective device to produce an innovative autologous material from dentin, which is capable of predictable viable bone tissue regeneration able to support prosthetic implant rehabilitation in edentulous sites.

Published
2022

73. Pilomotor seizures in autoimmune limbic encephalitis: description of two GAD65 antibodies- related cases and literature review

Author

Federica Pondrelli, Maria Pia Giannoccaro, Francesca Bisulli, Lorenzo Ferri, Veronica Menghi, Barbara Mostacci, Patrizia Avoni, Rocco Liguori, Paolo Tinuper, and Laura Licchetta

Subjects
Neurology, Limbic Encephalitis, Humans, Electroencephalography, Neurology (clinical), General Medicine, Autoantibodies, Autoimmune Diseases
Abstract

Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies.We selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP.Of 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.

Published
2022

74. Derived Dentin Graft as Autologous Bone Regeneration in Implant Surgery: A Histological and Radiographic Investigation

Author

Fabrizio Carini, Lorenzo Ferri, Giulia Coppola, Fabio Carini, Dario Monai, Carini, F, Ferri, L, Coppola, G, and Monai, D

Subjects
Tooth Transformer, Bone Regeneration, Histological Analysi, Dentin, Bone Graft, MED/28 - MALATTIE ODONTOSTOMATOLOGICHE, Implant Rehabilitation
Abstract

Background: This study has been conducted to evaluate the dentin regeneration potential as an autologous graft material for the preservation of the bone volume in the post-extraction socket. Tooth Transformer has been used as the device required to demineralize the dentin got from the extracted elements, which led to obtaining a granular material rich in collagen and growth factors. Methods: All 8 patients selected for the study underwent two surgical procedures. During the first surgery, the affected elements have been extracted, the Tooth Transformer protocol has been run, and the material has been grafted into the existing bone defects and post-extraction socket. After three months, the biopsy of the regenerated areas has been performed and the implants required for prosthetic rehabilitation were placed in the same site. For two of the 8 patients, the implant has been placed with the support of a surgical guide. Result: CBCT and histological analysis’ results after 3 months confirmed the actual replacement of grafted material and the regeneration of bone tissue suitable for implant rehabilitation. Conclusion: Thus, the Tooth Transformer proves to be an effective device to produce an innovative autologous material from dentin, which is capable of predictable viable bone tissue regeneration able to support prosthetic implant rehabilitation in edentulous sites.

Published
2022

76. Cognitive and Functional Connectivity Impairment in Post-COVID-19 Olfactory Dysfunction

Author

Lorenzo Muccioli, Giovanni Sighinolfi, Micaela Mitolo, Lorenzo Ferri, Magali Jane Rochat, Umberto Pensato, Lisa Taruffi, Claudia Testa, Marco Masullo, Pietro Cortelli, Raffaele Lodi, Rocco Liguori, Caterina Tonon, and Francesca Bisulli

Subjects
History, Neurology, Polymers and Plastics, Cognitive Neuroscience, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Business and International Management, Industrial and Manufacturing Engineering
Published
2022

77. Fistulotomy

Author

Paola Campennì, Lorenzo Ferri, Angelo Parello, Francesco Litta, Veronica De Simone, Angelo Alessandro Marra, and Carlo Ratto

Published
2022

78. Multicentre positive deviance to reduce adverse events and length of stay after pulmonary resection

Author

Andrew J E Seely, Zubair Ahmadzai, Daniel G French, Molly Gingrich, Daniel Jones, Caitlin Anstee, Najib Safieddine, Thomas K Waddell, Richard Malthaner, Lorenzo Ferri, Christian Finley, and Gail Darling

Subjects
Leadership and Management, Health Policy, Public Health, Environmental and Occupational Health
Abstract

BackgroundPostoperative adverse events (AEs) following pulmonary resection enormously impact patient well-being, length of stay (LOS) and healthcare costs. Standardised AE data collection can be used to identify positive outliers demonstrating positive deviance (PD) who may be helpful to inform the best practice. Here, we describe our initial experience of a novel quality improvement process using PD to reduce LOS and AEs.MethodsAE rates and LOS were collected from four centres (2014–2020) using a common dictionary. Surgeons repeatedly participated in 60 to 90 min seminars consisting of the following process: identify outcome and procedure targeted, review relevant best evidence literature, view all data anonymised by surgeon or centre (if multicentre), choose and reveal identity of best performance PD outliers, who discuss their management principles while all receive self-evaluation reports, followed by collegial discussion to generate consensus recommendations, voted by all. We assessed overall impact on AEs and LOS using aggregate data in a before/after analysis.ResultsA total of 131 surgeons (average 12/seminar) participated in 11 PD seminars (8 local and 3 multicentre), yielding 85 consensus recommendation (average 8/seminar). Median LOS following lobectomy decreased from 4.0 to 3.0 days (p=0.04) following local PD seminars and from 4.0 to 3.5 days (p=0.11) following multicentre seminars. Trends for reductions in multiple AE rates were also observed.ConclusionWhile limited by the longitudinal design, these findings provide preliminary support for this data-driven, collegial and actionable quality improvement process to help standardise and improve patient care, and merits further more rigorous investigation.

Published
2023

79. O-BN01 The para-oesophageal hernia symptom tool (post): A modified delphi consensus study

Author

Aiysha Puri, Nikhil Patel, Viknesh Sounderajah, Lorenzo Ferri, Ewen Griffiths, Donald Low, Nick Maynard, Carmen Mueller, Manuel Pera, Mark van Berge Henegouwen, David Watson, Giovanni Zaninotto, George Hanna, and Sheraz Markar

Subjects
Surgery
Abstract

Background Patients with a para-oesophageal hernia (POH) report a complex range of symptoms and quality of life (QOL) issues. Clinicians often utilise existing health related quality of life tools to (1) identify patients who are eligible for surgical management and (2) to evaluate the benefit of surgical intervention. However, the most commonly used tools for this purpose are not disease specific. As such, crucial POH specific symptoms which impact QOL may not be captured. In order to address this issue, a modified Delphi consensus study was undertaken to establish a HRQOL instrument specific to POH. Methods A two-round modified Delphi consensus study was conducted with a group of international experts. Participants were identified through (1) their authorship in landmark POH studies and (2) the professional networks of the study investigators. Prior to the Delphi process, a scoping survey was undertaken in order to generate a list of candidate items. Participants were asked to rate the items’ importance in assessing patients with POH using a 5-point Likert scale. The a priori threshold for inclusion was 80% for scores of 4 or 5. If consensus was not achieved, the item was carried through to the next round. Results The candidate list of items consisted of 64 symptoms, refined to 20 for inclusion within the first modified Delphi round. Four symptoms; ‘difficulty getting solid foods down’, ‘chest pain after meals’, ‘difficulty getting liquids down’ and ‘shortness of breath only after meals’, reached consensus threshold of 80% in the first round and one additional symptom, ‘early feeling of fullness after eating’, reached consensus in the second. A total of 26 participants took part in the first and 24 in the second round. These five symptoms have been identified to form the initial version of the Para-Oesophageal Hernia Symptom Tool (POST). Conclusions POST is the first tool that aims to capture POH-specific symptoms that impact upon HRQOL. Prior to clinical use, this tool will be presented in international patient workshops to assess its construct validity. Following this, we aim to assess the content validity of the tool through a longitudinal study in a cohort of patients with POH who are undergoing repair. We hope that this tool will serve as a decision support tool for clinicians who are evaluating the risk-benefit of surgical intervention in this cohort of patients.

Published
2021

80. Changes in Perioperative Platelet Lymphocyte Ratio Predict Survival in Oesophago-Gastric Adenocarcinoma

Author

James Tankel, Alexander Calderone, Jose Luis Ramirez Garcia-Luna, Carmen L. Mueller, Sarah Najmeh, Jonathan Spicer, David Mulder, Lorenzo Ferri, and Jonathan Cools-Lartigue

Subjects
Oncology, Surgery
Abstract

Platelet to lymphocyte ratio (PLR) is associated with survival in oesophageal cancer. We explored whether PLR changes during different stages of treatment correlate with survival outcomes.A retrospective single-centre study was performed. Consecutive patients who received neoadjuvant chemotherapy followed by surgery for oesophageal adenocarcinoma were identified. Changes in PLR were calculated during two time periods: the first spanning the neoadjuvant period (T1); the second the perioperative period (T2). Differences in PLR were calculated for clinicopathological variables during both T1 and T2 and for variables with regards to their association with median overall survival (OS). Variables found to be significant on univariate analysis were included in a multivariate Cox regression model. Using ROC analysis, optimal cut-offs for PLR changes were identified and plotted on a Kaplan-Meir curve.Of the 370 patients identified, 110 (29.7%) were included in the analysis. During T1 a positive correlation was noted between higher positive lymph node ratio and PLR change. During T2, PLR change was positively higher in patients who suffered major postoperative complications. Median survival for the cohort as a whole was 42.3 months and 5-year OS was 57.3%. Survival at 5 years was associated with lower PLR changes during T2. On univaraite analysis, median OS was significantly less for patients with a tumour size3 cm, poor differentiation and change in PLR ≥ 43.4 during T2. The latter two variables remained significant on multivariate analysis. Using the same PLR threshold, the survival curve comparing changes in PLR during T2 remained statistically significant.Perioperative PLR changes are highly prognostic of survival outcomes in patients treated for oesophageal adenocarcinoma.

Published
2021

81. Epilepsy With Auditory Features: From Etiology to Treatment

Author

Alessandro Furia, Laura Licchetta, Lorenzo Muccioli, Lorenzo Ferri, Barbara Mostacci, Stefania Mazzoni, Veronica Menghi, Raffaella Minardi, Paolo Tinuper, Francesca Bisulli, Furia A., Licchetta L., Muccioli L., Ferri L., Mostacci B., Mazzoni S., Menghi V., Minardi R., Tinuper P., and Bisulli F.

Subjects
DEPDC5, Neurology, aphasic seizure, auditory hallucinations, mTOR, auditory hallucination, epilepsy, LGI1, Neurology. Diseases of the nervous system, Neurology (clinical), RC346-429, aphasic seizures
Abstract

Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered, LGI1, was thought to be predominant. However, increasing evidence now points to a multifactorial etiology, as familial and sporadic EAF share a virtually identical electro-clinical characterization and only a few have a documented genetic etiology. Patients with EAF usually have an unremarkable neurological examination and a good response to antiseizure medications. However, it must be underscored that total remission might be lower than expected and that treatment withdrawal might lead to relapses. Thus, a proper understanding of this condition is in order for better patient treatment and counseling. Further studies are still required to further characterize the many facets of EAF.

Published
2021

82. 464 IS OPEN LEFT THORACO-ABDOMINAL ESOPHAGECTOMY A VIABLE OPTION IN THE ERA OF MINIMALLY INVASIVE ESOPHAGECTOMY?

Author

Fredrik Klevebro, Piers R Boshier, Carmen Mueller, Jonathan Cools-Lartigue, Lorenzo Ferri, and Donald E Low

Subjects
Gastroenterology, General Medicine
Abstract

The aim of the study was to evaluate short-term and oncological outcomes of left thoracoabdominal esophagectomy (LTE) compared to minimally invasive esophagectomy for cancer of the esophagus and gastroesophageal junction. LTE facilitates complete resection of esophageal cancer particularly for bulky tumors, but there are concerns that this approach is associated with significant morbidity. Methods Prospectively entered esophagectomy databases from two high volume North American centers were reviewed for patients undergoing LTE or MIE in the 2012–2018. Patient demographics, tumour characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 247 patients were included in the study, LTE was applied in 170 (68.8%) patients, and MIE in 77 (31.2%) patients. Results LTE patients had more neoadjuvant treatment (LTE = 78.2%, MIE = 34.2%, P 2—LTE = 26.1%, MIE17.0%, P = 0.184), pulmonary complications (LTE = 31.9%, MIE = 20.0%, P = 0.085), pneumonia (LTE = 15.2%, MIE = 13.6%, P = 0.768), anastomotic leak (LTE = 7%, MIE = 10%, P = 0.396), or postoperative mortality (LTE = 0%, MIE = 1.3%, P = 0.140). Median length of stay was 7 days in both groups. R0 resection rate was 93.8% and 95.5% respectively (P = 0.631). Median number of resected lymph nodes was 24 for LTE and 22 for MIE (P = 0.226). LTE had more stage II-IV tumors (LTE = 67.8%, MIE = 40.7%, P Conclusion LTE was used for larger tumors with greater lymph node burden in patients that were more likely to have received neoadjuvant treatment compared to MIE. Despite this the postoperative morbidity was equal to that of MIE, with no difference in short-term or oncological results in this cohort.

Published
2021

83. 691 IS OPEN LEFT THORACO-ABDOMINAL ESOPHAGECTOMY A VIABLE OPTION IN THE ERA OF MINIMALLY INVASIVE ESOPHAGECTOMY?

Author

Fredrik Klevebro, Shiwei Han, Stephen Ash, C Mueller, Jonathan Cools-Lartigue, Nick Maynard, Lorenzo Ferri, and Donald Low

Subjects
medicine.medical_specialty, business.industry, Esophagectomy, medicine.medical_treatment, Invasive esophagectomy, Gastroenterology, Medicine, General Medicine, business, Surgery
Abstract

Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky tumors, but there are concerns that this approach is associated with significant morbidity. The aim of the current study was to evaluate short-term and oncological outcomes of left thoracoabdominal esophagectomy compared to minimally invasive esophagectomy for cancer of the esophagus and gastroesophageal junction. Methods Prospectively entered esophagectomy databases from three high volume centers were reviewed for patients undergoing LTE or MIE 2012–2018. Patient demographics, tumour characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 844 patients were included in the study, LTE was applied in 654 (77.5%) patients, and MIE in 190 (22.5%) patients. Results LTE patients had more neoadjuvant treatment (LTE = 74.5%, MIE = 64.9%, P = 0.027). There was no difference in overall postoperative complications (LTE = 61.9%, MIE = 64.6%, P = 0.517), severe complications (Clavien Dindo >IIIa (LTE = 26.6%, MIE 26.5%, P = 0.982), pneumonia (LTE = 29.8%, MIE = 26.3%, P = 0.349), anastomotic leak (LTE = 7.7%, MIE = 9.9%, P = 0.348), or in-hospital mortality (LTE = 1.5%, MIE = 2.1%, P = 0.584). Median length of stay was 11 days after LTE vs. 8 days after MIE (P Conclusion LTE was used for tumors with greater lymph node burden in patients that were more likely to have received neoadjuvant treatment compared to MIE. MIE was associated with significantly shorter length of hospital stay, however postoperative morbidity and Clavien-Dindo scores were equal to that of MIE in this cohort.

Published
2021

85. Subcortical Myoclonus in Coronavirus Disease 2019: Comprehensive Evaluation of a Patient

Author

Giada Rossini, Francesca Rondelli, Maria Guarino, Pietro Cortelli, Lorenzo Ferri, Lorenzo Muccioli, Muccioli L., Rondelli F., Ferri L., Rossini G., Cortelli P., and Guarino M.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Neurology, medicine.disease, Virology, nervous system diseases, Pathogenesis, Cytokine release syndrome, Neurology, mental disorders, SARS-CoV-2, cytokine release syndrome, pathogenesis, neurophysiology, neurological, medicine, Neurology (clinical), medicine.symptom, business, Myoclonus
Abstract

Myoclonus has been reported as a possible manifestation of coronavirus disease 2019 (COVID-19), yet its neurophysiology andpathogenesis were poorly investigated. We describe a middle-aged man with COVID-19 who underwent extensive examinations for his disabling myoclonus.

Published
2020

86. Abstract 3068: Identify targetable molecular drivers of chemotherapy resistance in gastroesophageal adenocarcinoma

Author

Mingyang Kong, Swneke Bailey, Veena Sangwan, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

Introduction: Gastroesophageal adenocarcinoma (GEA) is one of the most lethal malignancies worldwide. Even with the standard-of-care chemotherapy, 40% of the patients are innately resistant and half of the initial responders develop acquired resistance. The molecular mechanisms underlying the development of resistance in GEA remain largely unknown. Methods: 30 GEA patients who received chemotherapy were included in this cohort. Both pre-and post-treatment primary tissues were collected to generate patient-derived organoids (PDOs). 29 PDOs were treated with chemotherapeutic agents and the cell viability was measured. We also evaluated the correlation between ex-vivo drug responses of PDOs and in-patient clinical responses. Data obtained from whole-exome (WES) and RNA sequencing of the primary tumor and their PDOs were analyzed to identify targetable molecules associated with chemo-resistance. Results: After treatment, the cell viability of the PDOs obtained from chemo-resistant patients was significantly higher than that of chemo-sensitive patients. The variant allele frequency of the PDOs recapitulated their parental tumors. WES of one patient tumor revealed an increased copy number of EGFR, and their PDOs showed high sensitivity to an EGFR inhibitor in the subsequent drug screens. Furthermore, 40% of chemo-sensitive patients had mutations in one or more genes belonging to the adhesion G protein-coupled receptors (GPCRs) family. The adenylate cyclase-activating G protein-coupled receptor signaling pathway was found to be significantly activated only in chemo-sensitive patients. Single-cell RNA sequencing of pre-and post-treatment tissue revealed a broadly shifted transcriptome in epithelial cells. Patients with upregulated cell stemness genes including CTNNB1, MYC, ETS2, and KLF4 had disease recurrence 6 months post-surgery, while patients with unaltered or downregulated stemness genes remain disease-free 18 months until today. Conclusion: Our PDOs not only reflected the genetic profile of primary tumors but also recapitulated patient responses to chemotherapy. Genomic analysis revealed that mutations in a few GPCR genes might have a role in increased sensitivity to chemotherapy. In addition, the transcriptomic analysis showed stemness genes were associated with disease recurrence. Our GEA PDO platform allows the identification and the subsequent verification of resistant-conferring targets, providing insight for novel therapeutic combinations. Funding: This project is supported by the Cancer Research Society (CCS), and the Department of Defence (DoD), USA. Citation Format: Mingyang Kong, Swneke Bailey, Veena Sangwan, Lorenzo Ferri. Identify targetable molecular drivers of chemotherapy resistance in gastroesophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3068.

Published
2022

87. Abstract 2625: Personalized chemotherapy treatments for microsatellite instable tumors

Author

Adam Hoffman, Sanjima Pal, Veena Sangwan, and Lorenzo Ferri

Subjects
Cancer Research, Oncology
Abstract

Introduction: Esophagogastric adenocarcinomas with microsatellite instability (MSI) high status often display chemoresistance, as the current therapies are ineffective. It is hypothesized that the poor response of MSI-high esophagogastric adenocarcinomas to therapies is due to the extensive genomic mutational heterogeneity, which can be overcome by identifying, stratifying, and targeting multiple genetic alterations concurrently. The goals of this project are to: 1) Identify a matched retrospective cohort of 20 MSI-high to 20 microsatellite stable organoids, derived from biobanked tumor tissue. 2) Analyze mismatch repair protein function/loss, to confirm that the primary tumor microsatellite status is recapitulated in 3D organoid models. 3) Test standard of care chemotherapies, and explore alternative approaches to prevent chemoresistance by evaluating targeted agents based on genomic sequencing. Methods: Patient-derived organoids grow for ~14 days, after which they are enzymatically disrupted and plated in Matrigel. I will confirm that the organoid models accurately represent clinal response, by treating them with the same chemotherapy received by the patient. 10 different drug concentrations are added in triplicate using a drug dispenser, then after 72 hours, organoid viability is determined with a plate reader. Results: Genomic characterization of 13/226 MSI-high cases has been conducted with a 234 gene gastric cancer specific panel to identify and target genomic alterations. Preliminary robotic drug screens guided by these mutation profiles have been conducted, yielding promising alternative treatments. Conclusions: By targeting the particular mutations found in MSI-high patients, it could help explain the chemoresistance mechanism, so promising personalized treatment approaches for esophagogastric adenocarcinomas can be clinically implemented. Sources of Funding: This project is funded by the Inez and Willena Beaton Award in Oncology, valued at $7,500 and provided by the RI-MUHC. The operating grants that support the research are $120,000 over 2 years from the Cancer Research Society, and $1,200,000 USD over 3 years given by the Department of Defense. Citation Format: Adam Hoffman, Sanjima Pal, Veena Sangwan, Lorenzo Ferri. Personalized chemotherapy treatments for microsatellite instable tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2625.

Published
2022

88. Effect of neutrophil extracellular traps on tumor lymph nodes

Author

Xin SU, Ariane Brassard, Iqraa Dhoparee-Doomah, Ramin Rohanizadeh, Betty Giannias, France Bourdeau, Veena Sangwan, Roni Rayes, Jonathan Spicer, Lorenzo Ferri, and Jonathan Cools-Lartigue

Subjects
Cancer Research, Oncology
Abstract

4033 Background: In most human cancers, regional lymph nodes (LNs) are the first sites of metastasis. In addition to being an important part of the tumor staging system, with the advent of novel therapies, lymph node metastasis has become a crucial clinical intervention point before distant metastasis, the leading cause of cancer-associated deaths. To initiate metastasis, the conditions of LNs need to be optimized for tumor cell deposition and growth. This process is believed to be mediated by the activation of immune cells including polymorphonuclear neutrophils (PMNs). However, the cellular mechanism is not well defined. Our early observations suggest that PMNs and neutrophil extracellular traps (NETs), DNA comprising structures that are extruded in response to inflammatory cues, are associated with adverse oncologic outcomes. Thus, one potential mechanism of increased LN metastasis is that tEVs recruit PMNs and propend NETs formation. Methods: Human tissue micro-arrays (TMAs) of gastroesophageal (GEA) cancer patients were stained with PMN and NETs markers and quantified by HALO software. C57BL/6 or pad4-/- mice were injected with B16F10 or H59 cells alone or treated with neutrophil elastase inhibitor (NEi) or PMN depletion antibody. LN sections were stained with NETs markers and quantified by ImageJ (NIH). Results: In the study of 175 GEA cancer patients, lymphatic NET deposition was observed in both tumor infiltrated lymph nodes and tumor negative lymph nodes. We also demonstrated high LN NETs deposition was associated with reduced survival, even in the absence of overt metastasis ( p=0.03). Next, we sought to investigate the dynamic and the consequence of LN NETs deposition using animal models. We found that LN Neutrophil Recruitment and NET deposition happens in a pre-metastatic manner. Moreover, LN metastasis was abrogated through different kinds of NETs inhibition (neutrophil depletion, pad4 knockout and NEi treatment, n=10, p

Published
2022

89. Endoscopic pyloromyotomy in minimally invasive esophagectomy: a novel approach

Author

Yehonatan, Nevo, Alexander, Calderone, Anitha, Kammili, Cyril, Boulila, Stephane, Renaud, Jonathan, Cools-Lartigue, Jonathan, Spicer, Carmen, Mueller, and Lorenzo, Ferri

Subjects
Esophagectomy, Gastroparesis, Postoperative Complications, Treatment Outcome, Esophageal Neoplasms, Pyloromyotomy, Humans, Minimally Invasive Surgical Procedures, Pylorus, Retrospective Studies
Abstract

Pyloric drainage procedures, namely pyloromyotomy or pyloroplasty, have long been considered an integral aspect of esophagectomy. However, the requirement of pyloric drainage in the era of minimally invasive esophagectomy (MIE) has been brought into question. This is in part because of the technical challenges of performing the pyloric drainage laparoscopically, leading many surgical teams to explore other options or to abandon this procedure entirely. We have developed a novel, technically facile, endoscopic approach to pyloromyotomy, and sought to assess the efficacy of this new approach compared to the standard surgical pyloromyotomy.Patients who underwent MIE for cancer from 01/2010 to 12/2019 were identified from a prospectively maintained institutional database and were divided into two groups according to the pyloric drainage procedure: endoscopic or surgical pyloric drainage. 30-day outcomes (complications, length of stay, readmissions) and pyloric drainage-related outcomes [conduit distension/width, nasogastric tube (NGT) duration and re-insertion, gastric stasis] were compared between groups.94 patients were identified of these 52 patients underwent endoscopic PM and 42 patients underwent surgical PM. The groups were similar with respect to age, gender and comorbidities. There were more Ivor-Lewis esophagectomies in the endoscopic PM group than the surgical PM group [45 (86%), 15 (36%) p 0.001]. There was no significant difference in the rate of complications and readmissions. Gastric stasis requiring NGT re-insertion was rare in the endoscopic PM group and did not differ significantly from the surgical PM group (1.9-4.7% p = 0.58).Endoscopic pyloromyotomy using a novel approach is a safe, quick and reproducible technique with comparable results to a surgical PM in the setting of MIE.

Published
2021

90. Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis

Author

Veena, Sangwan, Luai, Al-Marzouki, Sanjima, Pal, Vivian, Stavrakos, Malak, Alzahrani, Dorothy, Antonatos, Yehonatan, Nevo, Sophie, Camilleri-Broët, Roni, Rayes, France, Bourdeau, Betty, Giannias, Nicholas, Bertos, Swneke, Bailey, Simon, Rousseau, Jonathan, Cools-Lartigue, Jonathan D, Spicer, and Lorenzo, Ferri

Subjects
Lipopolysaccharides, Toll-Like Receptor 4, Stomach Neoplasms, Escherichia coli, Animals, Humans, Adenocarcinoma, Peritoneum, Peritoneal Neoplasms
Abstract

Surgical resection, the cornerstone of curative intent treatment for gastric adenocarcinoma, is associated with a high rate of infection-related post-operative complications, leading to an increased incidence of metastasis to the peritoneum. However, the mechanisms underlying this process are poorly understood. Lipopolysaccharide (LPS), an antigen from Gram-negative bacteria, represents a potential mechanism via induction of local and systemic inflammation through activation of Toll-like receptor (TLR). Here, we use both a novel ex vivo model of peritoneal metastasis and in vivo animal models to assess gastric cancer cell adhesion to peritoneum both before and after inhibition of the TLR4 pathway. We demonstrate that activation of TLR4 by either LPS or Gram-negative bacteria (E. coli) significantly increases the adherence of gastric cancer cells to human peritoneal mesothelial cells, and that this increased adherence is abrogated by inhibition of the TLR4 signal cascade and downstream TAK1 and MEK1/2 pathways. We also demonstrate that the influence of LPS on adherence extends to peritoneal tissue and metastatic spread. Furthermore, we show that loss of TLR4 at the site of metastasis reduces tumor cell adhesion, implicating the TLR4 signaling cascade in potentiating metastatic adhesion and peritoneal spread. These results identify potential therapeutic targets for the clinical management of patients undergoing resection for gastric cancer.

Published
2021

92. PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism with mono- or bi-allelic MMACHC epimutations

Author

Serena Motta, Jean-Louis Guéant, Giancarlo Parenti, Maria Alice Donati, Giancarlo la Marca, Sabrina Malvagia, Catia Cavicchi, David-Alexandre Trégouët, Céline Chéry, Marta Daniotti, Silvia Falliano, Amelia Morrone, Alessia Gozzini, Miriam Rigoldi, Serena Gasperini, Renzo Guerrini, Francesca Furlan, Francesca Menni, Abderrahim Oussalah, Pierre-Emmanuel Morange, Concetta Meli, Albina Tummolo, Lorenzo Ferri, Gestionnaire, HAL Sorbonne Université 5, Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Naples Federico II = Università degli studi di Napoli Federico II, Azienda Ospedaliero-Universitaria Policlinico 'Gaspare Rodolico', Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Meyer Children's Hospital [Florence, Italie], Università degli Studi di Firenze = University of Florence (UniFI), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Napoli Federico II, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, Locus (genetics), Homocystinuria, Compound heterozygosity, Methylmalonic aciduria and homocystinuria, 03 medical and health sciences, Secondary epimutation, 0302 clinical medicine, Neonatal Screening, Genetics, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Allele, Molecular Biology, Genetics (clinical), Genetic testing, Epi-cblC, medicine.diagnostic_test, business.industry, Research, cblC disease, Infant, Newborn, Expanded newborn screening (NBS), Peroxiredoxins, DNA Methylation, medicine.disease, MMACHC, Human genetics, 3. Good health, Promoter hypermethylation, Vitamin B 12, 030104 developmental biology, CpG island, cblC type, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, CBLC, business, Oxidoreductases, 030217 neurology & neurosurgery, Metabolism, Inborn Errors, Developmental Biology
Abstract

Background The role of epigenetics in inborn errors of metabolism (IEMs) is poorly investigated. Epigenetic changes can contribute to clinical heterogeneity of affected patients but could also be underestimated determining factors in the occurrence of IEMs. An epigenetic cause of IEMs has been recently described for the autosomal recessive methylmalonic aciduria and homocystinuria, cblC type (cblC disease), and it has been named epi-cblC. Epi-cblC has been reported in association with compound heterozygosity for a genetic variant and an epimutation at the MMACHC locus, which is secondary to a splicing variant (c.515-1G > T or c.515-2A > T) at the adjacent PRDX1 gene. Both these variants cause aberrant antisense transcription and cis-hypermethylation of the MMACHC gene promotor with subsequent silencing. Until now, only nine epi-cblC patients have been reported. Methods We report clinical/biochemical assessment, MMACHC/PRDX1 gene sequencing and genome-wide DNA methylation profiling in 11 cblC patients who had an inconclusive MMACHC gene testing. We also compare clinical phenotype of epi-cblC patients with that of canonical cblC patients. Results All patients turned out to have the epi-cblC disease. One patient had a bi-allelic MMACHC epimutation due to the homozygous PRDX1:c.515-1G > T variant transmitted by both parents. We found that the bi-allelic epimutation produces the complete silencing of MMACHC in the patient’s fibroblasts. The remaining ten patients had a mono-allelic MMACHC epimutation, due to the heterozygous PRDX1:c.515-1G > T, in association with a mono-allelic MMACHC genetic variant. Epi-cblC disease has accounted for about 13% of cblC cases diagnosed by newborn screening in the Tuscany and Umbria regions since November 2001. Comparative analysis showed that clinical phenotype of epi-cblC patients is similar to that of canonical cblC patients. Conclusions We provide evidence that epi-cblC is an underestimated cause of inborn errors of cobalamin metabolism and describe the first instance of epi-cblC due to a bi-allelic MMACHC epimutation. MMACHC epimutation/PRDX1 mutation analyses should be part of routine genetic testing for all patients presenting with a metabolic phenotype that combines methylmalonic aciduria and homocystinuria.

Published
2021

93. Multicenter evaluation of use of dried blood spot compared to conventional plasma in measurements of globotriaosylsphingosine (LysoGb3) concentration in 104 Fabry patients

Author

S. Feriozzi, Amelia Morrone, R. Mignani, M.L. Della Bona, C. L. Cirami, Lorenzo Ferri, Serena Gasperini, Federico Pieruzzi, G. la Marca, Serena Motta, E. Derwishi, B. Trezzi, Maria Alice Donati, Walter Borsini, Marta Daniotti, Sabrina Malvagia, Malvagia, S, Ferri, L, Della Bona, M, Borsini, W, Cirami, C, Derwishi, E, Feriozzi, S, Gasperini, S, Motta, S, Mignani, R, Trezzi, B, Pieruzzi, F, Morrone, A, Daniotti, M, Donati, M, and La Marca, G

Subjects
Male, 0301 basic medicine, Electrospray ionization, Clinical Biochemistry, Globotriaosylceramide, 030105 genetics & heredity, 03 medical and health sciences, chemistry.chemical_compound, Liquid chromatography–mass spectrometry, medicine, Humans, globotriaosylsphingosine, Bland–Altman plot, liquid chromatography-tandem mass spectrometry, Sphingolipids, Fabry disease, Chromatography, Filter paper, Biochemistry (medical), LysoGb3, General Medicine, Venous blood, medicine.disease, dried blood spot, Dried blood spot, 030104 developmental biology, chemistry, alpha-Galactosidase, Female, Dried Blood Spot Testing, Glycolipids, Biomarkers
Abstract

Objectives Fabry disease (FD) is an X-linked lysosomal storage disorder, resulting from a deficiency of the enzyme α-galactosidase A, responsible for breaking down glycolipids such as globotriaosylceramide and its deacylated derivative, globotriaosylsphingosine (LysoGb3). Here, we compare the levels of LysoGb3 in dried blood spots (DBS) and plasma in patients with classic and late-onset phenotypes. Methods LysoGb3 measurements were performed in 104 FD patients, 39 males and 65 females. Venous blood was collected. A portion was spotted onto filter paper and another portion separated to obtain plasma. The LysoGb3 concentrations in DBS and plasma were determined by highly sensitive electrospray ionization liquid chromatography tandem mass spectrometry. Agreement between different matrices was assessed using linear regression and Bland Altman analysis. Results The method on DBS was validated by evaluating its precision, accuracy, matrix effect, recovery, and stability. The analytical performances were verified by comparison of a total of 104 paired DBS and plasma samples from as many FD patients (representing 46 GLA variants). There was a strong correlation between plasma and the corresponding DBS LysoGb3 concentrations, with few exceptions. Discrepancies were observed in anemic patients with typically low hematocrit levels compared to the normal range. Conclusions The method proved to be efficient for the rapid analysis of LysoGb3. DBS provides a convenient, sensitive, and reproducible method for measuring LysoGb3 levels for diagnosis, initial phenotypic assignment, and therapeutic monitoring in patients with FD.

Published
2021

94. Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Author

Stephen R Knight, Catherine A Shaw, Riinu Pius, Thomas M Drake, Lisa Norman, Adesoji O Ademuyiwa, Adewale O Adisa, Maria Lorena Aguilera, Sara W Al-Saqqa, Ibrahim Al-Slaibi, Aneel Bhangu, Bruce M Biccard, Peter Brocklehurst, Ainhoa Costas-Chavarri, Kathryn Chu, Anna Dare, Muhammed Elhadi, Cameron J Fairfield, J Edward Fitzgerald, Dhruv Ghosh, James Glasbey, Mark I. van Berge Henegouwen, J.C. Allen Ingabire, T Peter Kingham, Marie Carmela Lapitan, Ismaïl Lawani, Bettina Lieske, Richard Lilford, Janet Martin, Kenneth A McLean, Rachel Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Francesco Pata, Thomas Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya Riad, Hosni Khairy Salem, Joana Simões, Richard Spence, Neil Smart, Stephen Tabiri, Hannah Thomas, Thomas G Weiser, Malcolm West, John Whitaker, Ewen M Harrison, Arben Gjata, Maria Marta Modolo, Sebastian King, Erick Chan, Sayeda Nazmun Nahar, Ade Waterman, Dominique Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol Sokolov, Venerand Barendegere, Gerald Ekwen, Arnav Agarwal, Qinyang Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques Bake, Jakov Mihanovic, Kamila Kuncarová, Julius Orhalmi, Hosni Salem, Jyri Teras, Aristotelis Kechagias, Alexis P Arnaud, Judith Lindert, Vasileios Kalles, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Zsolt Baranyai, Basant Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip Alexander, Sunil Kumar Venkatappa, C Pramesh, Radhian Amandito, Christina Fleming, Luca Ansaloni, Gianluca Pellino, Ahmed M. Altibi, Ibrahim Nour, Intisar Hamdun, Ali M. Ghellai, Donatas Venskutonis, Tomas Poskus, Justas Zilinskas, Precious Malemia, Yong Yong Tew, Elaine Borg, Sarah Ellul, fatima Zahraa Wafqui, David W Borowski, Anne Sophie van Dalen, Cameron Wells, Harissou Adamou, Adesoji Ademuyiwa, Adewale Adisa, Kjetil Søreide, Sara Al Saqqa, Osaid Alser, Haya Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr Major, António Sampaio Soares, Matei Razvan Bratu, Andrey Litvin, Armen Vardanyan, JC Allen Ingabire, Ahmad Gudal, Naif Albati, Jovan Juloski, Miran Rems, Sarah Rayne, Stephanie Van Straten, Yoshan Moodley, Irene Ortega Vázquez, Jaime Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar Homeida, Yucel Cengiz, Daniel Clerc, Muhammad Alshaar, Hanen Bouaziz, Yuksel Altinel, Matthew Doe, Maryna Freigofer, Ella Teasdale, Rakan Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan Ashfaq, Ijeoma Azodo, Gabriela Wagner, Ivan Trostchansky, Mayaba Maimbo, David Linyama, Helidon Nina, Amanda Zeko, Claudio Gabriel Fermani, Santiago Villalobos, Federico Carballo, Pablo Farina, Sebastian Guckenheimer, Marilla Dickfos, Ankit Ajmera, Chester Chong, Ralph Gourlay, Sikandar Hussaini, Yi Jia Lee, Adeeb Majid, Peter Martin, Rebecca Miles, Owen James Morris, Jamie Phua, William Ridley, Tarunpreet Saluja, Ryan Renxin Tan, Jen Teh, Anna Wells, Bharti Arora, Qaasim Dollie, Debbie Ho, Yanru Ma, Omattage Mahasha Perera, Anthony Truong, Amanda Caroline Dawson, Bryan Lim, Upuli Pahalawatta, Jacqueline Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea Yeoh, Lillian Charman, Andrew Drane, Sharon Laura, Charmaine Chu Wen Lo, Amy Mozes, Rita Poon, Hao Han Tan, Ellen Wall, Prakshi Chopra, Jasmine De Giovanni, Bal Dhital, Brian Draganic, Alexander Duller, Jonathan Gani, Yao Kuan Goh, Jun Young Jeong, Brendan McManus, Prakash Nagappan, Peter Pockney, Anya Rugendyke, Mahsa Sarrami, Stephen Smith, Vanessa Wills, Hsu Ven Wong, Geoffrey Ye, Geoffrey Zhang, Ethan Brooker, Daniel Feng, Bonnie Lau, Carlin Ngai, Sarah Birks, David Gyorki, Jaime Otero de Pablos, Ali Abbosh, Chris Gillespie, Ahmed Mahmoud, Bianca Kwan, Joshua Lawson, Andrea Warwick, Janne Bingham, Andrew J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan Ellaby-Hall, Ben Finlay, Emily Humphries, Jade Pisaniello, Monique Pisaniello, Salma Salih, Tarik Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola Hayward, Kartik Iyer, Guy Maddern, Gian Andrea Prevost, Naga Annapureddy, Krishna Pranathi Settipalli, Jeremy Yeo, Lucy Hempenstall, Lily Pham, Shaun Purcell, Cherry Talavera, Ashish I Vaska, Gurpreet Chaggar, Phillip Chrapko, Annelise Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame Ctercteko, James French, Houchen Gong, Martijn Gosselink, Thuvarahan Jegathees, Ivan Jin, Michelle Kalachov, Kathryn Kiefhaber, Katherine Lee, Jason Luong, Steven Phan, Henry Pleass, Kelly Veale, Zhi Zeng, Angela Au, Ashe DeBiasio, Idy Deng, Jananee Myooran, Amrita Nair, Peter Stewart, Anton Stift, Lukas Walter Unger, Kerstin Wimmer, Nabila Ahmed, Syed Hasan, Saber Rahman, Margaret O'Shea, Greg Padmore, Adrian Peters, Pietro Perduca, Guenda Pulcina, Nicolas Tinton, Frederic Buxant, Elsa Dabin, Giulia Garofalo, Francis Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako Motlaleselelo, Omphile Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia Batashki, Nikolai Damianov, Vladislav Stoyanov, Dragomir Dardanov, Svilen Maslyankov, Plamen Petkov, George Todorov, Evgeni Zhivkov, Aygulya Akisheva, Miguel Angel Castilla Moreno, Geno Genov, Ivelina Ilieva, Tsvetomir Ivanov, Martin Karamanliev, Azhar Khan, Emil Mitkov, Tsanko Yotsov, Boyko Atanasov, Nikolay Belev, Mihail Slavchev, Carlos Nsengiyumva, Elgan Jones, Simon Stock, Steve Kyota, James Brown, Tresor Mabanza K., Lemery Nigo Samuel, Chidi Otuneme, Ngwang Prosper, Franklin Umenze, Marylise Boutros, Natasha Caminsky, Sinziana Dumitra, Richard Garfinkle, Dominique Morency, Ebram Salama, Alexander Banks, Lorenzo Ferri, Haitian He, Amit Katz, Alexander Sender Liberman, Sarkis Meterissian, Allison Pang, Elena Parvez, Usmaan Hameed, Fahima Osman, Sangita Sequeira, Natalie Coburn, Alisha Jaffer, Paul Karanicolas, Matthew Mosseler, Reilly Musselman, Xinyuan Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina Guzman, Sebastian Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul Camelo, Andrea Gonzalez, Alejandro González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe Gonzalez, Andres Isaza-Restrepo, Laura Nino- Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin Tsandiraki, Damir Jemendžic, Branislav Kocman, Oliver Šuman, Renata Canic, Darko Jurišic, Ivana Karakas, Ana Krizanovic Rupcic, Vlatka Pitlovic, Josip Samardžic, Mario Kopljar, Ivan Bacic, Edgar Domini, Robert Karlo, Danijela Miljanic, Andrea Simic, Mariam Ahmed, Majdi Al Nassrallah, Rabiya Altaf, Talal Amjad, Ruba Eltoum, Heba Haidar, Alhassan Hassan, Omar Khalil, Marwan Qasem, Rommel Ramesh, Gautham Sajith, Maham Wisal, Jan Žatecký, Michele Bujda, Katerina Jirankova, Ales Paclik, Aya Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-sawy, Ahmed Moustafa ElFayoumy, Nourhan Elghareeb, Nourhan Ahmed Esmat, Ahmed Fadel, Abdullah Habater, Heba Hamdy, Amr Hefni, Marwa Kamal, Norhan Mohamed Abobakr, Ahmed Sayed, Nancy Shaker, Ehab Taha, Hoda Tharwat, Omar Zakaria, Ibrahem Abdelmotaleb, Ali Al-Dhufri, Hamza S. Al-Himyari, Enas El sheikh, Asmaa Eldmaty, Aya Elkhalawy, Ahmed M.Elkhashen, Kithara Magdy, Safa Mostafa, Habib Doutoum Sadia, Mohamed mahmoud Saleh, Dina Samir, Mohamed Yahia Mohamed Ali, Mahmoud A. Nassar, Samar Abdelhady, Aly Abdelrazek, Israa Abdelsalam, Aya El-Sawy, Eman Essam, Mohamed Gadelkarim, Khaled Ghaly, Mohamed Hassabalnaby, Rana Masarani, Nourhan Mohamed Shaaban, Ahmed Sabry, Menatalla Salem, Nourhan Akram Soliman, Diaaaldin Zahran, Moustafa Ramadan Abou El.soud, Esraa Tarek Badr, Hala Borham, Nehal Elmeslemany, Mohammad Elsayed, Fawzia Elsherif, Sara Eslam, Gehad Gaber, Sondos Ibrahim, Yara Kamh, Abdelrahman Mahmoud, Shimaa gamal Mohamed, Eman Morshedy, Cinderella Omar, Fatima Salem Soliman, Shaza Abdelkawy, Naglaa Abdelmohsen, Mahmoud Abdelshakour, Ahmed Dahy, Norhan Gamal, Mohammed Gamal, Ahmad Hasan, Helal Hetta, Nehad Mousa, Mohamed Omar, Somia Rabie, Mahmoud Saad, Bakeer Saleh, Marwa Sayed Mohamed, Muhammad Shawqi, Heba Abdelhady Mousa, Mostafa Alnoury, Mohamed Elbealawy, Ahmed Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah Ghonaim, Fawzy Hgag, Mohamed Ibrahim, Mahmoud Morsy, Mohamed Reda Loaloa, Ahmed Refaat, Hadeer Samir, Fatma Shahien, Mohamed Sobhy, Fathy Sroor, Esraa Abdellatif, Marina Adel, Amr Abdelghani Afifi, Eman Afifi, Marco Antaky, Amr Dawoud, Naira El Zoghby, Amira El-remaily, Ali Abdelazez Elzanfaly, Ahmed Gadallah, Fatma Alzahraa Gamal, Omar Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak Munir, Omar Shazly, Esraa Taha, Karim Wilson, Sawsan Adel, Asmaa Ali, Esraa Eid, Esraa Elhelow, Marwa Elmahdy, Bassant Elshatby, Amany Hossam el-din Zakaria, Ahmad Hossny, Eman Ibrahim, Ahmed M.Yonis, Maram Metwalli, Basant Yousry, Esraa Zid, Mina A Yacoub, Ahmed Abdelhakim, Nervana Abouelsoad, Mo'min Alkhatib, Ahmed Ashraf, Alaa Ashraf, Yasmin Elazab, Mahmoud Elfanty, Osama Elkabir, Mai Elsayed, Ahmed Elshimy, Hager Elsobky, John Eskander, Ahmed Gad, Ward Hamsho, Noura Khaled Abdelwahed, Menna Magdy, Dalia Moharam, Abeer Osama, Shereen Ramadan, Radwa Roum, Taqwa Sayed, Tarneem Shehada, Ahmed Mohy Zidan, Khalid Abbas, Amr Ali, Mohamed Attia, Mohamed Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed Elfallal, Hossam Elfeki, Ahmed Elkhadragy, Sameh Emile, Helmy Ezzat, Hasnaa Hosni, Islam Mansour, Waleed Omar, Gehad Othman, Kareem Sadek, Mostafa Shalaby, Noura Shehab-Eldeen, Rawda Anas khalifa, Helmy Badr, Mostafa Eldeep, Ahmed Eldeep, Amany Eldoseuky mohammed, Salwa Khallaf, Eman Magdy Hegazy, Rokia Mahmoud, Pola Mikhail, Mahmoud Morsi, Sara Mowafy, Dina Raafat, Amina Safy, Marwa Sera, Ahmed shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber Ahmed, Shireen Gaafar, Fatma Ibrahim negm, Mina Lapic, Ahmed Maher, Hagar Mahmoud, Ahmed Mostafa, Mohamed Samir, Fatma Samy, Nourhan Semeda, Hind I. Shalaby, Alaa El-taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed Hussein, Ahmed.A. Kandil, Mf Moawad, Ayat Allah Nasser Hamamah, Mostafa Soliman, Mohamed Abdelkhalek, Noura Abdelmaksoud Tawakel, Ahmed Mohamed Abdelwahed, Alrawy Abdou, Khalid Atallah, Mohammed Yasser Elsherbeny, Eman Emara, Mohamed Hamdy, Omar Hamdy, Amira Haron, Salma Ismail, Islam Hany Metwally, Nihal Mohamed Hamed Elgaml, Ahmed Nassar, Basel Refky, Mirna Sadek, Mahmoud Saleh, Asmaa Yunes, Mai Zakaria, Mohammed Zuhdy, Notila Fayed, Mohammed Mustafa Hassan Mohammed, Sander Kütner, Priit Melnik, Indrek Seire, Toomas Ümarik, Eppu Ainoa, Verner Eerola, Hanna Koppatz, Laura Koskenvuo, Ville Sallinen, Sini Takala, Jevgeni Katunin, Arto Turunen, Niki Christou, Muriel Mathonnet, Vincent Lavoue, Krystel Nyangoh Timoh, Lucie Soulabaille, Romain Lesourd, Aude Merdrignac, Laurent Sulpice, Benoît André, Elodie Chantalat, Charlotte Vaysse, Bertrand Dousset, Sebastien Gaujoux, Gregory Martin, Octavian Clonda, Domantas Juodis, Klaus Kienle, Andras Mravik, Samuel Palmer, Gabor Szabadhegyi, Anita Eseenam Agbeko, Solomon Gyabaah, Frank Enoch Gyamfi, Nuhu Naabo, Atta Owusu senior, Joseph Yorke, Frank Owusu, Francis Abantanga, Theophilus Teddy Kojo Anyomih, Abdul-Jalilu Mohammed Muntaka, Emmanuel Owusu Abem, Mohammed Sheriff, Paul M. Wondoh, Dimitrios Balalis, Dimitrios Korkolis, Georgios Gkiokas, Eirini Pantiora, Theodosios Theodosopoulos, Argyrios Ioannidis, Konstantinos Konstantinidis, Sofia Konstantinidou, Nikolaos Machairas, Anna Paspala, Anastasia Prodromidou, Christos Chouliaras, Konstantinos Papadopoulos, Ioannis Baloyiannis, Ioannis Mamaloudis, George Tzovaras, Ioanna Akrida, Maria-Ioanna Argentou, Stylianos Germanos, Evangelos Iliopoulos, Ioannis Maroulis, George Skroubis, George Theofanis, Christos Chatzakis, Orestis Ioannidis, Lydia Loutzidou, Panagiotis Karathanasis, Nikolaos Michalopoulos, Charalampos Theodoropoulos, Dimitrios Theodorou, Tania Triantafyllou, Zoe Garoufalia, Natasha Hasemaki, Michalis Kontos, Gregory Kouraklis, Stylianos Kykalos, Theodore Liakakos, Eustratia Mpaili, Alexandros Papalampros, Dimitrios Schizas, Athanasios Syllaios, Ekaterini Christina Tampaki, Antonios Tsimpoukelis, Maria Ioanna Antonopoulou, Eirini Deskou, Dimitrios K. Manatakis, Dimitrios Papageorgiou, Menelaos Zoulamoglou, Christos Anthoulakis, Michalis Margaritis, Nikolaos Nikoloudis, Veronica Campo, André Ceballos, Mario-Andrés Flores, Waleska Giron, Donghyun Ko, Gabriel Martinez, Verónica Rivera Lara, Nataly Rueda, Andres Sanchez, Jorge Carlos Guillermo Tejeda Garrido, Alvaro Eduardo Alvarez Rivera, Elvis Benjamin Bamaca Ixcajoc, Lilian Elizabeth Barreda Zelaya, Patricia Chacòn-Herrera, Ligia Margarita Corea Ruiz, Guillermo Echeverria-Davila, Mario Garcia, Danilo García, Edgar Fernando Gutiérrez Mayen, Noriega José, Nery Mazariegos, Diego Méndez, Michael Paniagua Espinoza, David Bardos, Marton Benke, Kristof Illes, Balint András Kokas, Réka Szabó, Akhila Appukuttan, Anjitha Asok, Vijaykumar D.k, Kapil Malik, Praveen Ravishankaran, Ritesh Tapkire, Guru Moorthy, Joyner Abraham, Ramesh Muthuvel, John Alapatt, Abhay Kattepur, Nizamudheen Pareekutty, Mebanshanbor Garod, Caleb Harris, Cliff Wanniang, Ashish Gupta, Deepak Nehra, Sanjeev Parshad, Rajgopal Acharya, Rajendra Badwe, Manish Bhandare, Urvashi Jain, Karishma Kirti, Nita Nair, Shailesh Shrikhande, Purvi Thakkar, Premkumar Anandan, Archana C S, Arun Holenarasipur Narasannaiah, Tejaswi Jagarlamudi, Rashmi M R, Mallikarjuna Manangi, Abhishek Raghavendra, K. Seshagiri Rao, Vinay S, Vinay Sajjan, Aneesh Shenoy, Santhosh Shivashankar Chikkanayakanahalli, Kavya Tharanath, Sushmita V, Peter Adidharma, Raksheeth Agarwal, Phebe Anggita Gultom, Ghafur Rasyid Arifin, Matthew Billy, Zatira Elfizri, Alessa Fahira, Devi Felicia, Triana Hardianti Gunardi, Nadya Johanna, Nadia Rahmadiani Nugrahadi, Sonar Soni Panigoro, Siti Rahmayanti, Retta Catherina Sihotang, Santi Yuanita Brata, Hadi Winoto, Nastaran Barati, Manoochehr Karami, Hamidreza Khorshidi, Homa Naderifar, Mazin A. Abdulla, Maggie Coleman, Ronan J Doherty, Rob Hannon, Brenda Murphy, Aine Stakelum, Des Winter, Lylas Aljohmani, Richard Farnan, Yeshey Seldon, Tanna Tan, Shriya Varghese, Mohammad Alherz, Muaaz Ather, Mohammad Bajilan, Vivien Graziadei, Isobel Pilkington, Omar Quidwai, Paul Ridgway, Haaris Shiwani, Abd al-Rahman Tahir, Eimear Blunnie, Daniel Burke, Niall Kennedy, Kate Macdonagh, Maeve O'Neill, Siobhan Rooney, Giuseppe Falco, Guglielmo Ferrari, Simone Mele, Gabriela Elisa Nita, Lara Ugoletti, Maurizio Zizzo, Gianmaria Confalonieri, Giovanni Pesenti, Fulvio Tagliabue, Gianluca Baronio, Deborah Ongaro, Giacomo Pata, Bruno Compagnoni, Renato Salvadori, Lucio Taglietti, Nicola D'Alessandro, Pierpaolo Di Lascio, Giovanni Pascale, Luca Bortolasi, Tommaso Campagnaro, Massimo Carlini, Giorgio Lisi, Davide Lombardi, Corrado Pedrazzani, Domenico Spoletini, Giulia Turri, Paola Violi, Donato Francesco Altomare, Fabrizio Aquilino, Nicola Musa, Vincenzo Papagni, Arcangelo Picciariello, Leonardo Vincenti, Dario Andreotti, Savino Occhionorelli, Matteo Tondo, Stefano Maria Massimiliano. Basso, Riccardo Cirelli, Marco Enrico Mario Maino, Guglielmo Niccolò Piozzi, Emanuele Picone, Rosa Scaramuzzo, Giovanni Sinibaldi, Alfonso Amendola, Lorenzo Anastasio, Luigi Bucci, Emanuele Caruso, Antonio Castaldi, Sara Di Maso, Vincenza Paola Dinuzzi, Giovanni Esposito, Maria Gaudiello, Mariano Cesare Giglio, Paola Antonella Greco, Gaetano Luglio, Andrea Manfreda, Ester Marra, Federica Mastella, Gianluca Pagano, Roberto Peltrini, Vincenzo Pepe, Michele Sacco, Viviana Sollazzo, Giovanni Spiezio, Ettore Cianchetti, Nunzia Menduni, Michele Maria Carvello, Francesca Di Candido, Antonino Spinelli, Fabio Corsi, Luca Sorrentino, Fabio Marino, Emanuele Luigi Giuseppe Asti, Luigi Bonavina, Emanuele Rausa, Martina Asta, Andrea Belli, Francesco Bianco, Carmela Cervone, Paolo Delrio, Armando Falato, Andrea Fares Bucci, Rita Guarino, Ugo Pace, Daniela Rega, Emilia De Luca, Gaetano Gallo, Giuseppe Sammarco, Giuseppe Sena, Giuseppina Vescio, Letizia Santandrea, Giampaolo Ugolini, Davide Zattoni, Nicola Chetta, Gaetano Logrieco, Serafino Vanella, Gianluca Garulli, Nicola Zanini, Andrea Bondurri, Francesco Cammarata, Francesco Colombo, Diego Foschi, Giulia Maria Beatrice Lamperti, Anna Maffioli, Gianluca Matteo Sampietro, Al'ona Yakushkina, Gloria Zaffaroni, Enrico Cicuttin, Maria Grazia Sibilla, Harmony Impellizzeri, Marco Inama, Gianluigi Moretto, Sylvie Mochet, Elisa Ponte, Antonella Usai, Stefano Mancini, Andrea Sagnotta, Luigi Solinas, Elisa Bolzonaro, Nicolò Tamini, Gianluca Curletti, Raffaele Galleano, Michele Malerba, Sofia Campanella, Gianfranco Cocorullo, Francesco Colli, Paolino De Marco, Nicolò Falco, Tommaso Fontana, Leonel jospin Kamdem Mambou, Antonella La Brocca, Leo Licari, Brenda Randisi, Giovanna Rizzo, Giulia Rotolo, Giuseppe Salamone, Roberta Tutino, Paolina Venturelli, Stefano Malabarba, Alessandro Sgrò, Ivan Vella, Bruno Cirillo, Daniele Crocetti, Giorgio De Toma, Pierfrancesco Lapolla, Andrea Mingoli, Paolo Sapienza, Angela Belvedere, Stefania Bianchini, Margherita Binetti, Arianna Birindelli, Valeria Tonini, Mauro Podda, Fabio Pulighe, Michele De Rosa, Lorenzo Bono, Felice Borghi, Paolo Geretto, Maria Carmela Giuffrida, Corrado Lauro, Alessandra Marano, Luca Pellegrino, Paola Salusso, Diego Sasia, Michela Campanelli, Alberto Realis Luc, Mario Trompetto, Roberto Cardia, Nicola Cillara, Antonio Nicola Giordano, Antonio Costanzo, Mario Alessandro Giovilli, Luca Turati, Silvestro Canonico, Guido Sciaudone, Francesco Selvaggi, Lucio Selvaggi, Nader Albsoul, Ahmad AlBsoul, Ala'a Aldeen Alkhatib, Osama Alsallaq, Justin Z. Amarin, Rami Ayoub, Isam Bsisu, M S El Muhtaseb, Mohammad Jabaiti, Jamal Melhem, Yasmeen Z. Qwaider, Mohammad Hasan Salameh, Ahmad Suleihat, Haya H. Suradi, Mohammad Alammarin, Almoutuz Aljaafreh, Mohammad Bani hani, Zeina Bani hani, Farah Bani Hani, Toqa Fahmawee, Shadi Hamouri, Cyrine Katanani, Ra'fat Tawalbeh, Tamara Tawalbeh, Hassan Zawahrah, Mohamad K. Abou Chaar, Lana Abusalem, Mahmoud Al-Masri, Hani Al-Najjar, Lutfi Barghuthi, Zahra Ahmed, Adnan Maulana, Omar Ngotho, Charbel Kamau, Aruyaru Stanley Mwenda, Fridah Bosire, Elizabeth Mwachiro, Robert Parker, Ian Simel, Kimutai Sylvester, Abdulmunem Ahmed Mustafa Althini, Sofian Elbarouni, Aya Elseed Elbeshina, Ahmed Gwea, Ans Malek, Wedad Albashir Masoud Farag, Abdulwahab Abdalei, Abu Baker Abdel Malik, Areej Abo-khammash, Ma'aly Abuhlaiga, Nour Adnan, Marwa Albaggar, Asma Alfitory, Asma Aljanfi, Fakhruddin Almuzghi, Zohoor Altumei, Fatima Alzabti, Hana Ashoushan, Mohamed Assalhi, Joma Azzubia, Sondos Bnhameida, Malik Delhen, Houssein Elshafei, Hana Elteir, Fatima Esbaga, Abdel Aziz Gobbi, Fatma Hamouda, Hamdan Hilan, Rania Ismail, Fieruz Jebran, Muataz Kasbour, Galia Maderi, Saja Mohammad, Burooj Mohammed, Habib Murtadi, Hamassat Mustafa, Mohamed Rajab, Sarah Trenba, Mariam Wafaa, Eman Al Sagheir, Alabas Almigheerbi, Ahmed Alzahaf, Sumayyah Ghayth Bahroun, Najah Ben Dallah, Mahmoud Elshaibani, Haitem Eswaye, Maha Karar, Samah Omar, Eman Younes, Maha Younes, Dafer Zreeg, Saleh Abujamra, Firas Ashour, Mala Elgammudi, Wesal Omar F. Aljadidi, Enas Saddouh, Randa Sharif, Aya Alabuzidi, AbdulMawlay Alwerfally, Sarra Aribi, Fatma Bibas, Taha Elfaituri, Yasmine Elhajjaji, Ala Khaled, Wegdan Khalil, Tesneem Layas, Enas Soula, Ahmed Tarek, Muad fathi khalleefah Abu hallalah, Hazem Abdelkarem Ahmed, Tagwa Alsharef, Abdulsalam Ali Ben Saoud, Tasnim El Gharmoul, Ahmed Elhadi, Safa Elrais, Abdulhalim Shebani, Heba Zarti, Asaid Zeiton, Marijus Ambrazevicius, Nerijus Kaselis, Migle Stakyte, Oleg Aliosin, Agne Cizauskaite, Sarunas Dailidenas, Vitalijus Eismontas, Migle Kybransiene, Vitalija Nutautiene, Narimantas Samalavicius, Dainius Simcikas, Algirdas Slepavicius, Albinas Tamosiunas, Nerijus Ubartas, Paulius Zeromskas, Saulius Bradulskis, Edvinas Dainius, Juozas Juocas, Egle Kubiliute, Juozas Kutkevicius, Aurimas Opolskis, Audrius Parseliunas, Andrejus Subocius, Egle Virbickaite, Diana Zuikyte, Algirdas Bogusevicius, Kristina Buzaite, Daiva Cepuliene, Ieva Cesleviciene, Vaidotas Cesna, Jolanta Gribauskaite, Povilas Ignatavicius, Mantas Jokubauskas, Monika Liugailaite, Ernest Margelis, Ruta Mazelyte, Lina Pankratjevaite, Matas Pažusis, Agne Rackeviciute, Justina Saladyte, Monika Škimelyte, Vygintas Šlenfuktas, Monika Sudeikyte, Algimantas Tamelis, Tomas Vanagas, Žygimantas Žumbakys, Aivaras Atkociunas, Audrius Dulskas, Justas Kuliavas, Justas Birutis, Sigitas Paškevicius, Mindaugas Šatkauskas, Donatas Danys, Matas Jakubauskas, Lina Jakubauskiene, Marius Kryzauskas, Vytautas Lipnickas, Gabija Makunaite, Fanjandrainy Rasoaherinomenjanahary, Herizo Rasolofonarivo, Luc Hervé Samison, Bitiel Banda, Vanessa Msosa, Ahmad Imran Ahmad Izzuddin, Andre Das, Ying Yee Gan, Tan Shong Sheng, Jia yng Siaw, Mohd Fadliyazid Ab Rahim, Dyg Zahratul Hamrak Abang Jamari, Nurfariza Che Husin, Muhd Yusairi Kamarulzaman, Yi Ping Lim, Nil Amri Mohamed Kamil, Mohd Razeen Mohd Hassan, Saidah Mohd Sahid, Johari Mustafa, Elaine Hui Been Ng, Wan Khamizar Wan Khazim, Ng Chang Ern, P.g. Lingeshan, Syariz Ezuan Sulaiman, Sue Ean Ang, Muhammad Navid Bin Mohamad Sithik, Yih Jeng Cheong, Mahadevan Deva Tata, Law Jia Xian, Aravinthan Kadravello, I-Ern Koh, Li-Yen Ng, Yuki Julius Ng We Yong, Kandasami Palayan, Chi Xuan Sam, Phuah Siow Jin, Jeremy Tan Ern Hwei, Yita Tang, Alvin Zubin Ter, Michael Pak-Kai Wong, Andee Dzulkarnaen Zakaria, Zaidi Zakaria, Fitjerald Henry, Thyivya Kalaiselvan, Muhammad Fairuz Shah Abd Karim, Mohamed Rezal Abdul Aziz, Nora Abdul Aziz, Tak Loon Khong, Peng Choong Lau, Hiong Chin Lim, April Camilla Roslani, Jonathan Chen Ken Seak, Sui-Weng Wong, Lai Fen Wong, Leow Yeen Chin, Mercy Chinemerem Anyanwu, Zachary Busuttil, Thomas Calleja, Kurt Lee Chircop, Ruth Cutajar, Andrew Michael Dimech, Joseph Galea, Kiara Gascon Perai, Ruth Gatt, Lisa Kelman, Elizabeth Micallef, Favour Nwolu, Kim Sammut, Joanna Thompson, Sean Warwicker, Matthew Zammit, Fernando Cordera, Efraín Cruz González, Jorge Sánchez-García, Francisco José Barbosa Camacho, Francisco Javier Barrera López, Carlos Jose Zuloaga Fernandez del Valle, Eric Acosta, Iván Romarico González Espinoza, Perla Moreno, Ana Olivia Cortes-Flores, Clotilde Fuentes Orozco, Alejandro Gonzalez Ojeda, Samantha Corro Díaz González, Laura Martinez, Bonifacio Mosqueda Amador, Armando Novoa, Dennet Arturo Olazo Espejo, Alejandro Jimenez, Federico Lopez Rosales, Elva Gabriela Vanoye, Luis Alberto Garcia Gonzalez, Roberto Carlos Miranda-Ackerman, Manuel Solano-Genesta, Alethia Alvarez-Cano, Hector Hugo Romero-Garza, Heriberto Medina-Franco, Lorelí Mejía-Fernández, Noel Salgado-Nesme, Omar Vergara-Fernandez, Guadalupe Montserrat Gutiérrez-Mota, Francisco Xavier Hernandez Vera, Anabella Llantada Lopez, Gilberto Morgan Villela, Felipe de Jesus Ramirez Padilla, Walezka Tapia Marin, Mónica Martínez Maldonado, Ramses Sánchez Suárez, José Manuel Troche, Chaymae Benyaiche, Oumaima Outani, Souadka Amine, Amine Benkabbou, Anass Mohammed Majbar, Raouf Mohsine, Ali Rafik, Thida Oung, Moe Moe Tin, Philipp Plarre, Anna Alberga, Nina Sluiter, Jurriaan Tuynman, Robin Blok, Didem Cömert, Roel Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S. Al-Busaidi, Gabrielle Budd, Seung il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T. Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali SANI, Stephen Garba, Rebecca Hauwa SANI, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-srour, Sadi A. Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B. Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A. Albahnasawi, Asmaa' Abo mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A.Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R. Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu shua`ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario Vidal Meza, Gabriela Zavala, José Neiser Castillo Arrascue, Jomara Caroline Hidrogo Cabrera, José Julio Mariano Larrea vera, Miguel Osorio, Edgar Alcides Ylatoma Díaz, Mark Anthony Fontanilla, Joseph Roy Fuentes, Anna Leah Salazar, Genieve Dominguez, Marc Paul Lopez, Shiela Macalindong, Mark Augustine Onglao, Arjel Ramirez, Marie Dione Sacdalan, Mayou Martin Tampo, Gemma Leonora Uy, Jeremiah Mangahas, Kenneth Yabut, Joannes Paul Cañete, Bernalynn Eris Cansana, Ernes John Castro, Maria Kaiserin Lipana, Manuel Francisco Roxas, Vlu Jean Zara, Maciej Chrol, Paula Franczak, Michal Orlowski, Piotr Budzynski, Andrzej Budzynski, Pawel Bury, Agata Czerwinska, Jadwiga Dworak, Jacek Dziedzic, Michal Kisielewski, Jan Kulawik, Anna Lasek, Piotr Malczak, Marcin Migaczewski, Michal Pedziwiatr, Magdalena Pisarska, Dorota Radkowiak, Mateusz Rubinkiewicz, Anna Rzepa, Tomasz Skoczylas, Maciej Stanek, Katarzyna Truszkiewicz, Mateusz Wierdak, Marek Winiarski, Piotr Zarzycki, Anna Zub-Pokrowiecka, Piotr Kowalewski, Rafal Roszkowski, Maciej Waledziak, Miguel Tomé, Sara Patrocinio, Ines Guerreiro, Filipe Almeida, Xavier de Sousa, Nuno Monteiro, Maria Teresa Costa Santos, Daniela de Oliveira, Marta Lopes Serra, Daniela Morgado, Christian Neves, Ana Carolina Oliveira, Alice Pimentel, Sofia Silva, Márcia Carvalho, Lúcia Carvalho, Joana Magalhães, Leonor Matos, Tânia Monteiro, Carlota Ramos, Vanessa Santos, José Barbosa, Jose Costa-Maia, Vítor Devezas, Ana Fareleira, Cristina Fernandes, Diana Gonçalves, Henrique Mora, Marina Morais, Fabiana Silva de Sousa, Sara Catarino Santos, Ana Logrado, André Tojal, Edgar Amorim, Miguel F. Cunha, Ana Fazenda, João Pedro Melo Neves, Inês Isabel Sampaio da Nóvoa Gomes Miguel, Diogo Veiga, José Azevedo, Hugo Cardoso Louro, Mariana Leite, Maria Bairos Menezes, Bárbara Gama, Diana Brito, Marta Cristina Cruz Martins, André Graça e Magalhães, Ana Catarina Longras, Rita Lourenço, Diana Matos, Luis Castro, Filipa Policarpo, Joana Romano, Cristina Monteiro, Diogo Pinto, Marina Duarte, Sónia Fortuna Martins, Mariline Oliveira, Diogo Galvão, Lisandra Martins, Anaisa Silva, Viorel Taranu, Bárbara Vieira, Jessica Neves, Simone Oliveira, Hugo Ribeiro, Margarida Cinza, Rosa Felix, Arnaldo Machado, Joana Oliveira, Joana Patrício, Rita Pedroso de Lima, Mário Pereira, Miguel Rocha Melo, Cristina Velez, Alberto Abreu da Silva, Mariana Claro, Daniel Costa Santos, Andreia Ferreira, Hugo Capote, Daniela Rosado, Filipa Taré, Oriana Nogueira, Miguel Ângelo, José Miguel Baiao, Andreia Guimarães, João Marques, Miguel Nico Albano, Marta Silva, Ana Valente da Costa, Teresa Vieira Caroço, Sara Almeida Braga, Ines Capunge, Marta Fragoso, João Guimarães, Bruno Pinto, João Ribeiro, Miguel Angel, Guilherme Fialho, Monica Guerrero, Filipa Campos Costa, Diogo Cardoso, Vasco Cardoso, Magda Alves, Inês Estalagem, Tiago Louro, Cláudia Marques, Rita Martelo, Miguel Morgado, Rita Canotilho, Ana Margarida Correia, Pedro Martins, Mariana Peyroteo, João Gomes, Rita Monteiro, Manuela Romano, Daniela Macedo Alves, Rita Peixoto, Catarina Quintela, Maria João Jervis, Débora Melo, André Pacheco, Valter Paixão, Vera Pedro, Joana Pimenta, João Pimenta de Castro, Ana Rocha, Mircea Beuran, Cezar Ciubotaru, Bogdan Diaconescu, Sorin Hostiuc, Ionut Negoi, Bogdan Stoica, NA NA, Evgeny Anokhin, Georgy Kuznetsov, Giorgi Oganezov, Fedor Paramzin, Ekaterina Romanova, Valeryan Rutkovskii, Vasilii Rutkovskii, Mikhail Shushval, Mikhail Zabiyaka, Khasan Dzhumabaev, Valerii Ivanov, Zaman Mamedli, Sergey Achkasov, Artem Balkarov, Elnur Nabiev, Marat Nagudov, Evgeny Rybakov, Karina Saifutdinova, Oleg Sushkov, Lule Joseph, Isaac Ndayishimiye, Ntirenganya Faustin, Alphonse Zeta Mutabazi, Jean Paul Mvukiyehe, Vizir J.P Nsengimana, Carine Uwakunda, Mohammad Monir Abbas, Nouf Akeel, Murad Aljiffry, Kholoud Awaji, Ali Farsi, Ghader Jamjoum, Ahmad Khoja, Ashraf Maghrabi, Nadim Malibary, Mohammed Nassif, Abdulaziz Saleem, Abdullah Sultan, Wail Tashkandi, Hanaa Tashkandi, Nora Trabulsi, Mouhamadou Bachir Ba, Adja Coumba Diallo, Abdourahmane Ndong, Vladica Cuk, Uroš Jankovic, Sharon Zhiling Koh, Frederick Koh, Kuok Chung Lee, Kai Yin Lee, Sean Lee, Wei Qi Leong, Su Ann Lui, Prajwala Prakash, Jan Grosek, Gregor Norcic, Ales Tomazic, Nicolas Fitchat, Robert Jaich, Devorah Wineberg, Modise Zacharia Koto, Daniella Baiocchi, Damian Clarke, Christina Johanna Steenkamp, Sharon Bannister, Adam Boutall, Galya Chinnery, Anna Coccia, Angela Dell, Parveen Karjiker, Christo Kloppers, Nicholas Loxton, Tumi Mabogoane, Francois Malherbe, Eugenio Panieri, Shreya Rayamajhi, Tirsa van Wyngaard, Claire Warden, T E Madiba, Nivashen Pillay, Savannah Brooks, Charlise Kruger, Lisa Hannah Van Der Merwe, Ferhana Gool, Maahir Kariem, Heather Bougard, Nazmie Kariem, Fazlin Noor, Reantha Pillay, Leandi Steynfaardt, Lucía González González, José Miguel Marín Santos, Paula Martín-Borregón, Javier Martínez Caballero, Cristina Nevado García, Pastora Rodriguez Fraga, Gonzalo De Castro Parga, Maria Pilar Fernández Veiga, Lucía Garrido López, Hugo Infante Pino, Irene Lages Cal, Marta López Otero, Manuel Nogueira Sixto, Marta Paniagua García Señorans, Laura Rodríguez Fernández, Alejandro Ruano Poblador, Erika Rufo Crespo, Raquel Sanchez-Santos, Vincenzo Vigorita, Ester Alonso Batanero, Dorisme Asnel, Isabel Cifrian Canales, Elisa Contreras Saiz, Irene De Santiago Alvarez, Tamara Díaz Vico, Sebastian Fernandez Arias, Daniel Fernández Martínez, Carmen García Bernardo, Luis Joaquín García Flórez, Carmen Garcia Gutierrez, Manuel García Munar, Carlos Alberto Márquez Zorrilla Molina, Marta Merayo, José Luis Michi Campos, Maria Moreno Gijon, Jorge L. Otero-Diez, Jose Luis Rodicio Miravalles, Lorena Solar-Garcia, Aida Suárez Sánchez, Nuria Truan, Cristina Alejandre Villalobos, Yurena Caballero Díaz, Marta Jimenez, Dacil Montesdeoca, Antonio Navarro-Sánchez, Victor Vega, Juan Beltrán de Heredia, Zahira Gómez, Carlos Jezieniecki, Ana Patricia Legido Morán, Mario Montes-Manrique, Mario Rodriguez-Lopez, María Ruiz Soriano, Jeancarlos Trujillo Díaz, Andrea Vazquez Fernandez, Nuria Argudo, Miguel Pera, Laia Torrent Jansà, Melody García Domínguez, Ignacio Goded, Marta Roldón Golet, Issa Talal El-Abur, Alejandra Utrilla Fornals, Vanesa Zambrana Campos, Maria Del Mar Aguilar Martinez, Marina Bosch, Luis García-Catalá, Luis Sánchez-Guillén, Eva Artigau, Nuria Gomez Romeu, David Julià Bergkvist, Beatriz Espina Perez, Olga Morató, Carles Olona, Beatriz Diéguez, Alexander Forero-Torres, Manuel Losada, Segundo Gomez-Abril, Paula Gonzálvez, Rosario Martinez, Sergio Navarro Martínez, Carmen Payá-Llorente, Álvaro Pérez Rubio, Sandra Santarrufina Martinez, Juan Carlos Sebastián Tomás, Ramon Trullenque Juan, Alberto Gegúndez Simón, Paloma Maté, Maria Isabel Prieto-Nieto, Ines Rubio-Perez, Aitor Urbieta, Marina Vicario Bravo, David Abelló, Matteo Frasson, Alvaro Garcia-Granero, Alfredo Abad Gurumeta, Ane Abad-Motos, Elena Lucena-de Pablo, Beatriz Nozal, Javier Ripollés-Melchor, Rut Salvachúa, Esther Ferrero, Luis Garcia-Sancho Tellez, Antonio L. Picardo, Jose Alberto Rojo López, Laura Patricia Zorrilla Matilla, Carmen Cagigas Fernandez, Sonia Castanedo Bezanilla, José Estevez Tesouro, Maria Jose Fernandez-Diaz, Juan García Cardo, Marcos Gomez Ruiz, Erik Gonzalez-Tolaretxipi, Jaime Jimeno Fraile, Cristobal Poch, Montserrat Rodriguez-Aguirre, Noemí Troche Pesqueira, Maria Soledad Trugeda-Carrera, Javier de la Torre, Ruth Blanco-Colino, Eloy Espin-Basany, Martin Espinosa-Bravo, Clara Morales Comas, Eduardo Reyes Afonso, Joaquín Rivero Déniz, Christian Siso Raber, Mireia Verdaguer Tremolosa, Pramodh Chandrasinghe, Sumudu Kumarage, Nimeshi Wijekoon Arachchilage, Ahmed Abdalla Ahmed Elkamel, Mohammed A. Adam, Nina Blomme, Anders Thorell, Fredrik Wogensen, Andreas Älgå, Dhirar Ansarei, Fuat Celebioglu, Göran Heinius, Linda Nigard, Emil Pieniowski, Sandra Ahlqvist, Ida Björklund, Andreas Frånberg, Martina Håkansson, Karin Adamo, Oskar Franklin, Malin Sund, Rebecca Wiberg, Yvette Andersson, Abbas Chabok, Maziar Nikberg, Alexander Kugelberg, Claudia Canonica, Dimitrios Christoforidis, Fabrizio Fasolini, Paolo Gaffuri, Mauro Giuliani, Francesco Meani, Sotirios Georgios Popeskou, Silvia Pozza, Wiebke Wandschneider, Lorenz Peterer, Lukas Werner Widmer, Bernd Zimmermann, Panagiotis Bakoleas, Iris Chanousi, Lydia Charalampidou, Lukasz Filip Grochola, Franziska Heid, Sotirios Ntaoulas, Michail Outos, Georgios Peros, Hanna Podolska-Skoczek, Katharina Beate Reinisch, Christian Zielasek, Nicolas Demartines, Jérôme Gilgien, Amaniel Kefleyesus, Pénélope St-Amour, Arnaud Toussaint, Maryam Alhimyar, Bayan Alsaid, Amr Alyafi, Ahmad Alkhaledi, Basel Kouz, Ahmad Omarain, Yusra Al-Sabbagh, Haya Alkhatib, Samer Sara, Ahmad Alhaj, Aghyad Danial, Lama Kadoura, Sarah Maa Albared, Yamen Monawar, Louei Nahas, Barook Abd, Ahmad Saad, Habib Wakkaf, Hatem Bouzaiene, Montassar Ghalleb, Elif Akaydin, Ata Cem Akbaba, Onur Atakul, Ege Baltaci, Sevval Besli, Gökçen Burgu, Ulukan Cenal, Cansu de Muijnck, Hasan Can Demirkaya, Alper Dogruoz, Zeynep Ipek Gezer, Yasemin Gündogdu, Merve Kara, Hasan Kürsad Korkmaz, Gökalp Kagan Kurtoglu, Volkan Ozben, Berk Baris Ozmen, Ahmet Murat Pektas, Eda Kübra Sel, Nilüfer Yenidünya, Fuat Baris Bengur, Berke Mustafa Oral, Tahir Koray Yozgatli, Seymur Abdullayev, Mehmet Emin Gunes, Nuri Alper Sahbaz, Tuba Banaz, Kübra Kargici, Omer Faruk Kuyumcu, Erkan Yanikoglu, Merve Yesilsancak, Duygu Yilmaz, Melik Kagan Aktas, Ahmet Rencuzogullari, Arda Isik, Sezai Leventoglu, Ali Yalçinkaya, Osman Yüksel, Mustafa U Kalayci, Yasin Kara, Inanc Samil Sarici, Alp Akin, Gökçe nur Alemdag, Ekin Arslan, Bahadir Emre Baki, Muhammed Selim Bodur, Adnan Calik, Bahar Candas Altinbas, Irem Cihanyurdu, Oguz Erkul, Burak Gül, Ali Guner, Beyza Köse, Anil Semiz, Sule Sevim, Serkan Tayar, Kadir Tomas, Ozan yavuz Tüfek, Serdar Türkyilmaz, Mehmet Ulusahin, Arif Usta, Reyyan Yildirim, Sertaç Ata Güler, Ozan Can Tatar, Ecenur Varol, Busenur Kirimtay, Muhammed Uysal, Alp Yildiz, Emin Kose, Ahmet Burak Ciftci, Elif Çolak, Huseyin Eraslan, Gultekin Ozan Kucuk, Kürsat Yemez, Herman Lule, Mumbere Bienfait, Emmanuel Bua, Noella Okalany, Maksym Basarab, Oleksii Bielosludtsev, Kateryna Kolhanova, Kateryna Perepelytsia, Kateryna Romanukha, Dmytro Savenkov, Stanislav Siryi, Maksym Tereshchenko, Nezamai Viacheslav, Anton Volovetskyi, Andrey Kebkalo, Yegor Tryliskyy, Volodimir Tyselskiy, Eilidh Bruce, Bing Lun Chow, Emma Iddles, Sarah McGuckin, Nicola Newall, George Ramsay, Parivrudh Sharma, Caitlin Stewart, Jeremy Wong, Abdul Badran, Michael Bath, Fanny Belais, Eman Butt, Kaustuv Joshi, Milan Kapur, Mike Shaw, Adam Townson, Christopher Yee Khang Williams, Timothy Gray, Robert Greig, Mansoor Husain, Elspeth Murray, Ahmed Mustafa, Ashar Asif, Arya Gokul, Max Shah, Mabel Temisanren Akitikori, Alexandros Charalabopoulos, Sophie Davidson, Sinead McNally, Shamil Rupani, Fatema Juma, Sarah Catherine Mills, Laura Muirhead, Kate Sellars, Una Walsh, Oliver Warren, Alice Chambers, Richard Hunt, Stephen Boyce, Hannah Cornwall, Isabel Tol, Eleftherios Orestis Argyriou, Nicola Eardley, Meical Povey, Joanna M S Aithie, Ahmer Irfan, Mari-Claire McGuigan, Robert Starr, Craig Russell Warren, Jess Archibald, Georgia Kirby, Ivan Kisyov, Chun Kheng Khoo, Rachel Lee, Dana Photiou, Rowan Davis, Uday Prasad, P Zichu Yang, Jonathan Bird, Edmund Leung, Virginia Summerour, Chelise Currow, Jianshen Kiam, Gerald Jack Soon Tan, Anitha Muthusami, Ibifunke Pegba-Otemolu, Tomas Urbonas, Joseph Nunoo-Mensah, Edgaras Smolskas, Alex Boddy, Gianpiero Gravante, David Hunter, David Andrew, Amanda Koh, Amari Thompson, Lawrence Adams, Hollie A Clements, Kasun De Silva, Ogbonnia Ekpete, Seraj Haque, Scott Henderson, Bilal Ibrahim, Thummini Jayasinghe, Jennifer Livie, Keir Mailley, Gopikrishnan Nair, Daniel Tan, Caitlin Baggaley, Aleksander Dawidziuk, Bartosz Szyszka, Charlotte Barter, Nirav Gandhi, Karen Hassell, Samantha Hitchin, Jennett Kelsall, Eva Nagy, Ashrafun Nessa, Lisa Whisker, Fady Yanni, Mahmoud Ali, Deeksha Arora, Sunanda Hediwattege, Navam Kumarasinghe, Munir Rathore, Athula Tennakoon, Syed Mustafa Ali Ahmad, Oreoluwa Bajomo, Fahema Nadira, Valerio Celentano, Ewen Griffiths, Rama Santhosh Karri, Jason Kei Chak Mak, Michelle Pipe, Muhammad Iqbal Bhatti, Mohamed Rabie, Connor Boyle, David Hamilton, Aishath Mihuna, James Chean Khun Ng, Gary Nicholson, Agata Oliwa, Robert Pearson, Anna Rose, Shun Qi Yong, Catherine Boereboom, Michael Hanna, Catherine Walter, Thomas Samuel Greensmith, Rachel Mitchell, Eimear Monaghan, James Crawford, Susan Moug, James Blackwell, Hannah Boyd-Carson, Philip Herrod, Omar Al-Allaf, Miriam Beattie, Cameron Bullock, Shivang Burman, Gemma Clark, Nicolas Flamey, Oliver Flannery, Alexander Harding, Ben Kodiatt, Samuel Lawday, Shivani Mahapatra, Navin Mukundu Nagesh, Michael Ng, Dupinderjit Rye, Andrel Yoong, Laura Clark, Chris Deans, Monisha Edirisooriya, Emma Victoria Carrington, Tsz Lun Ernest Wong, Baasil Yusuf, Carla Chamberlain, Kathryn Duke, Elizabeth Kmiotek, Azel Botes, Natalie Condie, Timothy Schrire, Reena Shah, Iolo Thomas-Jones, Charlotte Yates, Natasha Anthony, Edward Matthews, Kapil Sahnan, James Tankel, Sally Tucker, Jasmine Winter Beatty, Paul Ziprin, William Duggan, Anastasia Kantartzi, Shruthi Sridhar, Rachel Alys Khaw, Prakhar Srivastava, Charlotte Underwood, Homero Alves do Canto Brum, Sharat Chopra, Laura Davis, Rebecca Hughes, Joshua Tulley, Justin Alberts, Thomas Athisayaraj, Mojolaoluwa Olugbemi, Kasim Ahmad, Claudia Chan, Gavin Chapman, Hannah Fleming, Benjamin Fox, Julia Grewar, Kate Hulse, Duncan Rutherford, Mackay Sinead, Scott Smith, Doug Speake, Peter G Vaughan-Shaw, Natasha Christodoulides, Simrit 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A., Abu shua'ib R., Abu Zainah B., AbuSirrees M., Babaa B., Barhoush O., Belal qadomi A., Daraghmeh L., Haji R., Khatatbeh A., Khatib L., Qarariah S., Quzmar Y., Safadi K., Salameh R., Hassan M., Herzallah S., Massad L., Nazzal A., Nazzal R., Escobar D., Machain V G.M., Rodriguez Gonzalez A., Chachaima Mar J.E., Chinchihualpa Paredes N.O., Cuba V., Lopez W., Niquen Jimenez M.M., Sanchez Bartra N.A., Sapallanay Ojeda O., Sequeiros D., Toscano Pacheco A., Vergara M., Abarca S., Alcorta R., Borda-Luque G., Eusebio Zegarra I.E., Lujan Lopez C., Marrufo M., Mogrovejo C., Nomura A., Rodriguez Angeles Y., Vidal Meza M.R., Zavala G., Castillo Arrascue J.N., Hidrogo Cabrera J.C., Larrea vera J.J.M., Osorio M., Ylatoma Diaz E.A., Fontanilla M.A., Fuentes J.R., Salazar A.L., Dominguez G., Lopez M.P., Macalindong S., Onglao M.A., Ramirez A., Sacdalan M.D., Tampo M.M., Uy G.L., Mangahas J., Yabut K., Canete J.P., Cansana B.E., Castro E.J., Lipana M.K., Roxas M.F., Zara V.J., Chrol M., Franczak P., 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Adam M., Blomme N., Thorell A., Wogensen F., Alga A., Ansarei D., Celebioglu F., Heinius G., Nigard L., Pieniowski E., Ahlqvist S., Bjorklund I., Franberg A., Hakansson M., Adamo K., Franklin O., Sund M., Wiberg R., Andersson Y., Chabok A., Nikberg M., Kugelberg A., Canonica C., Christoforidis D., Fasolini F., Gaffuri P., Giuliani M., Meani F., Popeskou S.G., Pozza S., Wandschneider W., Peterer L., Widmer L.W., Zimmermann B., Bakoleas P., Chanousi I., Charalampidou L., Grochola L.F., Heid F., Ntaoulas S., Outos M., Peros G., Podolska-Skoczek H., Reinisch K.B., Zielasek C., Demartines N., Gilgien J., Kefleyesus A., St-Amour P., Toussaint A., Alhimyar M., Alsaid B., Alyafi A., Alkhaledi A., Kouz B., Omarain A., Al-Sabbagh Y., Alkhatib H., Sara S., Alhaj A., Danial A., Kadoura L., Maa Albared S., Monawar Y., Nahas L., Abd B., Saad A., Wakkaf H., Bouzaiene H., Ghalleb M., Akaydin E., Akbaba A.C., Atakul O., Baltaci E., Besli S., Burgu G., Cenal U., de Muijnck C., Demirkaya H.C., Dogruoz A., Gezer Z.I., Gundogdu Y., Kara M., Korkmaz H.K., Kurtoglu G.K., Ozben V., Ozmen B.B., Pektas A.M., Sel E.K., Yenidunya N., Bengur F.B., Oral B.M., Yozgatli T.K., Abdullayev S., Gunes M.E., Sahbaz N.A., Banaz T., Kargici K., Kuyumcu O.F., Yanikoglu E., Yesilsancak M., Yilmaz D., Aktas M.K., Rencuzogullari A., Isik A., Leventoglu S., Yalcinkaya A., Yuksel O., Kalayci M.U., Kara Y., Sarici I.S., Akin A., Alemdag G.N., Arslan E., Baki B.E., Bodur M.S., Calik A., Candas Altinbas B., Cihanyurdu I., Erkul O., Gul B., Guner A., Kose B., Semiz A., Sevim S., Tayar S., Tomas K., Tufek O.Y., Turkyilmaz S., Ulusahin M., Usta A., Yildirim R., Guler S.A., Tatar O.C., Varol E., Kirimtay B., Uysal M., Yildiz A., Kose E., Ciftci A.B., Colak E., Eraslan H., Kucuk G.O., Yemez K., Lule H., Bienfait M., Bua E., Okalany N., Basarab M., Bielosludtsev O., Kolhanova K., Perepelytsia K., Romanukha K., Savenkov D., Siryi S., Tereshchenko M., Viacheslav N., Volovetskyi A., Kebkalo A., Tryliskyy Y., Tyselskiy V., Bruce E., Chow B.L., Iddles E., McGuckin S., Newall N., Ramsay G., Sharma P., Stewart C., Wong J., Badran A., Bath M., Belais F., Butt E., Joshi K., Kapur M., Shaw M., Townson A., Williams C.Y.K., Gray T., Greig R., Husain M., Murray E., Mustafa A., Asif A., Gokul A., Shah M., Akitikori M.T., Charalabopoulos A., Davidson S., McNally S., Rupani S., Juma F., Mills S.C., Muirhead L., Sellars K., Walsh U., Warren O., Chambers A., Hunt R., Boyce S., Cornwall H., Tol I., Argyriou E.O., Eardley N., Povey M., Aithie J.M.S., Irfan A., McGuigan M.-C., Starr R., Warren C.R., Archibald J., Kirby G., Kisyov I., Khoo C.K., Lee R., Photiou D., Davis R., Prasad U., Yang P.Z., Bird J., Leung E., Summerour V., Currow C., Kiam J., Tan G.J.S., Muthusami A., Pegba-Otemolu I., Urbonas T., Nunoo-Mensah J., Smolskas E., Boddy A., Gravante G., Hunter D., Andrew D., Koh A., Thompson A., Adams L., Clements H.A., De Silva K., Ekpete O., Haque S., Henderson S., Ibrahim B., Jayasinghe T., Livie J., Mailley K., Nair G., Tan D., Baggaley C., Dawidziuk A., Szyszka B., Barter C., Gandhi N., Hassell K., Hitchin S., Kelsall J., Nagy E., Nessa A., Whisker L., Yanni F., Ali M., Arora D., Hediwattege S., Kumarasinghe N., Rathore M., Tennakoon A., Ali Ahmad S.M., Bajomo O., Nadira F., Celentano V., Griffiths E., Karri R.S., Mak J.K.C., Pipe M., Bhatti M.I., Rabie M., Boyle C., Hamilton D., Mihuna A., Ng J.C.K., Nicholson G., Oliwa A., Pearson R., Rose A., Yong S.Q., Boereboom C., Hanna M., Walter C., Greensmith T.S., Mitchell R., Monaghan E., Crawford J., Moug S., Blackwell J., Boyd-Carson H., Herrod P., Al-Allaf O., Beattie M., Bullock C., Burman S., Clark G., Flamey N., Flannery O., Harding A., Kodiatt B., Lawday S., Mahapatra S., Mukundu Nagesh N., Ng M., Rye D., Yoong A., Clark L., Deans C., Edirisooriya M., Carrington E.V., Wong T.L.E., Yusuf B., Chamberlain C., Duke K., Kmiotek E., Botes A., Condie N., Schrire T., Shah R., Thomas-Jones I., Yates C., Anthony N., Matthews E., Sahnan K., Tankel J., Tucker S., Winter Beatty J., Ziprin P., Duggan W., Kantartzi A., Sridhar S., Khaw R.A., Srivastava P., Underwood C., Alves do Canto Brum H., Chopra S., Davis L., Hughes R., Tulley J., Alberts J., Athisayaraj T., Olugbemi M., Ahmad K., Chan C., Chapman G., Fleming H., Fox B., Grewar J., Hulse K., Rutherford D., Sinead M., Speake D., Vaughan-Shaw P.G., Christodoulides N., Kudhail S., Welch M., Husaini S.M., Lambracos S., Anyanwu C., Suresh R., Thomas J.S., Gleeson E., Platoff R., Saif A., Enumah Z., Etchill E., Gabre-Kidan A., Bernstein M., Carrano F.M., Connors J., Lynn P., Melis M., Newman E., Foster D.S., Perrone K., Titan A., Ahmad S., Bafford A.C.M.D., Dal Molin M., Hanna N., Zafar S.N., Hemmila M., Napolitano L., Wong J.J., Chandler J., Wood L., Wren S., Ottesen T., You L., Yu K., Arcienega Yanez M.D.P., Ferreira Fernandes M., Gonzalez D., Cubas S., Gonzalez M.C., Zubiaurre V., Demolin R., Giroff N., Sciuto P., Campos M., Rodriguez Cantera G., Deepika G., Simuchimba E., Bulaya A., Chibuye C., Chirengendure B., Kabale M.-R., Kabongo K., Munthali J., Mweso O., Pikiti F., Otieno J., Lai L.T., Blackman B., Subramaniam S., Karim R., Kok N., Lee Y.D., Ali S., Sinha A., Corrigan R., Barnes N., Wong F., Dennis G., Jedamzik J., Phillips E., Piette W., Van hentenryck M., Koco H., Lawani S., Kassa M.W., Santos Bezerra T., Gribnev P., Dimitrov D., Krastev P., Oum S., Bonghaseh D.T., Al Farsi M., Alsharqawi N., Acevedo V., Castillo Barbosa A.C., Giron F., Leon Rodriguez J.P., Kucan D., Rosko D., Barsic N., Zupan D., Hegazi A., Truncikova V., Fryba V., Mohamed M., Nagi A., Rashad Temerik A., Elshawy M.E., Mahmoud M.I., Anwar M., Rageh T., Elmokadem A., Gaballa K., Teppo S., Pengerma P., Ballouhey Q., Bergeat D., Weyl A., Hain E., Gyedu A., Yenli E., Osei-Poku D., Rompou V.-A., Zoikas A., Gaitanidis A., Koukis G., Perivoliotis K., Tavlas P., Galanos-Demiris K., Zografos G., Karavokyros I., Xanthopoulou G., Iordanidou E., Ayau F., Garcia A., Damjan P., Wason D., B L A., Rangganata E., Kamath P., O'Connor D.B., Pinto M., Perrone F., Tropeano F.P., Troilo F., Bossi D., Scala D., Pulitano L., Carella M., Pietrabissa A., Gori A., Giraudo G., De Simone V., Russo A.A., Braccio B., Al-Taher R., Athamneh S., Parker A., Sawiee A., Kattia A., Tababa O., Shaeeb Z., Syminas V., Jurgaitis J., Damuleviciene G., Svagzdys S., Razafimanjato N.N.M., Chieng Loo L., Tiong I.C., Wan Muhmad W.F., Vijeyan H., Li Ying T., Grech G., Arrangoiz R., Jimenez Ley V.B., Arizpe D., Lagunes Lara E., Castro Lopez E.V., Eaazim J., Gordinou de Gouberville M., Bastiaenen V., Rottier S., Nahab F., Ji M.Y., Seyoji M., Nwachukwu C., Emeghara O., Muhammed S.E., Idowu A., Sowemimo O., Ogundoyin O., Akande O., Lott A., Nadeem M., Laghari A.A., Loya A., Mushtaq H., Abdullah M.T., Abuhilal B., Atawneh M., Hamdan H., Alhabil B., Srour A., Mousa I., Da Silva Medina L., Bartosiak K., Ferreira P., Francisco V., Lemos R., Frutuoso L., Fernandes S., Fonseca T., Pereira J., Rachadell J., Torre A., Madeira Martins F., Carvalho A.C., Rodrigues Ferreira J., Ribeiro da Silva B., Devesa H., Vieira A., Monica I., Amaro M., Sousa D., Reia M., Louro J., Martins A., Dominguez J., Santos I., Freitas Oliveira N.M., Pereira J.C., Silva-Vaz P., Freire L., Escrevente R., Negoita V.M., Shakhmatov D., Nezerwa Y., Radulovic R., Obery G., Viljoen F., Mendes T., Suarez A., Moncada E., Fernandez-Hevia M., Curtis Martinez C., Gil Garcia J.M., Gonzalez Zunzarren M., Idris T., Eklov K., Grahn O., Amin L., Blomqvist M., Ajani C., Kraus R., Seeger N., Willemin M., Rayya F., Ayash M., Msouti R., Kannas I., Abazid E., Esper A., Slim S., Kavcar A.S., Aytac E., Dural A.C., Ilker A., Eray I.C., Kurnaz E., Altiner S., Tepe M.D., Sahin C., Savli E., Innocent A., Babirye L., Diachenko A., Hordoskiy V., Curry H., Chau C.Y.C., Robertson H., Lennon H., Loi L., Kirkham E., McCann C., Watts D., Gurung B., Wilson M., Tribedi T., Garofalo E., Zahra B., MacDonald S., Daniels I., Ng N., Khosla S., Olivier J., Yue 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V., Ye, G., Zhang, G., Brooker, E., Feng, D., Lau, B., Ngai, C., Birks, S., Gyorki, D., Otero de Pablos, J., Abbosh, A., Gillespie, C., Mahmoud, A., Kwan, B., Lawson, J., Warwick, A., Bingham, J., Cockbain, A. J., Dudi-Venkata, N. N., Ellaby-Hall, J., Finlay, B., Humphries, E., Pisaniello, J., Pisaniello, M., Salih, S., Sammour, T., Abd Wahab, H. H., De Silva, A., Hayward, N., Iyer, K., Maddern, G., Prevost, G. A., Annapureddy, N., Settipalli, K. P., Yeo, J., Hempenstall, L., Pham, L., Purcell, S., Talavera, C., Vaska, A. I., Chaggar, G., Chrapko, P., Cocco, A., Coulter-Nile, S. M. C. J., Ctercteko, G., French, J., Gong, H., Gosselink, M., Jegathees, T., Jin, I., Kalachov, M., Kiefhaber, K., Lee, K., Luong, J., Phan, S., Pleass, H., Veale, K., Zeng, Z., Au, A., Debiasio, A., Deng, I., Myooran, J., Nair, A., Stewart, P., Stift, A., Unger, L. W., Wimmer, K., Ahmed, N., Hasan, S., Rahman, S., O'Shea, M., Padmore, G., Peters, A., Perduca, P., Pulcina, G., Tinton, N., Buxant, F., Dabin, E., Garofalo, G., Dossou, F., Gnangnon, F. H. R., Imorou Souaibou, Y., Motlaleselelo, P., Tlhomelang, O., Lima Buarque, I., Mendonca Ataide Gomes, G., Vieira Barros, A., Batashki, I., Damianov, N., Stoyanov, V., Dardanov, D., Maslyankov, S., Petkov, P., Todorov, G., Zhivkov, E., Akisheva, A., Castilla Moreno, M. A., Genov, G., Ilieva, I., Ivanov, T., Karamanliev, M., Khan, A., Mitkov, E., Yotsov, T., Atanasov, B., Belev, N., Slavchev, M., Nsengiyumva, C., Jones, E., Stock, S., Kyota, S., Brown, J., Mabanza, K. T., Nigo Samuel, L., Otuneme, C., Prosper, N., Umenze, F., Boutros, M., Caminsky, N., Dumitra, S., Garfinkle, R., Morency, D., Salama, E., Banks, A., Ferri, L., He, H., Katz, A., Liberman, A. 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A., Fadel, A., Habater, A., Hamdy, H., Hefni, A., Kamal, M., Mohamed Abobakr, N., Sayed, A., Shaker, N., Taha, E., Tharwat, H., Zakaria, O., Abdelmotaleb, I., Al-Dhufri, A., Al-Himyari, H. S., El sheikh, E., Eldmaty, A., Elkhalawy, A., M. Elkhashen, A., Magdy, K., Mostafa, S., Sadia, H. D., Saleh, M. M., Samir, D., Yahia Mohamed Ali, M., A. Nassar, M., Abdelhady, S., Abdelrazek, A., Abdelsalam, I., El-Sawy, A., Essam, E., Gadelkarim, M., Ghaly, K., Hassabalnaby, M., Masarani, R., Mohamed Shaaban, N., Sabry, A., Salem, M., Soliman, N. A., Zahran, D., Abou, El. soud M. R., Badr, E. T., Borham, H., Elmeslemany, N., Elsayed, M., Elsherif, F., Eslam, S., Gaber, G., Ibrahim, S., Kamh, Y., Mohamed, S. G., Morshedy, E., Omar, C., Salem Soliman, F., Abdelkawy, S., Abdelmohsen, N., Abdelshakour, M., Dahy, A., Gamal, N., Gamal, M., Hasan, A., Hetta, H., Mousa, N., Omar, M., Rabie, S., Saad, M., Saleh, B., Sayed Mohamed, M., Shawqi, M., Abdelhady Mousa, H., Alnoury, M., Elbealawy, M., Elshafey, A., Essam Ibrahim El Desouki Muhammad Ahmed, M., Ghonaim, M., Hgag, F., Ibrahim, M., Morsy, M., Reda Loaloa, M., Refaat, A., Samir, H., Shahien, F., Sobhy, M., Sroor, F., Abdellatif, E., Adel, M., Afifi, A. A., Afifi, E., Antaky, M., Dawoud, A., El Zoghby, N., El-remaily, A., Elzanfaly, A. A., Gadallah, A., Gamal, F. A., Hashem, O., Medhat Youssef, S., Muhammad Attyah, A., Munir, M., Shazly, O., Wilson, K., Adel, S., Ali, A., Eid, E., Elhelow, E., Elmahdy, M., Elshatby, B., Hossam el-din Zakaria, A., Hossny, A., Ibrahim, E., M. 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I., Veiga, D., Azevedo, J., Cardoso Louro, H., Leite, M., Bairos Menezes, M., Gama, B., Brito, D., Cruz Martins, M. C., Graca e Magalhaes, A., Longras, A. C., Lourenco, R., Matos, D., Castro, L., Policarpo, F., Romano, J., Monteiro, C., Pinto, D., Duarte, M., Fortuna Martins, S., Oliveira, M., Galvao, D., Martins, L., Silva, A., Taranu, V., Vieira, B., Neves, J., Oliveira, S., Ribeiro, H., Cinza, M., Felix, R., Machado, A., Oliveira, J., Patricio, J., Pedroso de Lima, R., Pereira, M., Rocha Melo, M., Velez, C., Abreu da Silva, A., Claro, M., Costa Santos, D., Ferreira, A., Capote, H., Rosado, D., Tare, F., Nogueira, O., Angelo, M., Baiao, J. M., Guimaraes, A., Marques, J., Nico Albano, M., Silva, M., Valente da Costa, A., Vieira Caroco, T., Almeida Braga, S., Capunge, I., Fragoso, M., Guimaraes, J., Pinto, B., Ribeiro, J., Angel, M., Fialho, G., Guerrero, M., Campos Costa, F., Cardoso, D., Cardoso, V., Alves, M., Estalagem, I., Louro, T., Marques, C., Martelo, R., Morgado, M., Canotilho, R., Correia, A. M., Martins, P., Peyroteo, M., Gomes, J., Monteiro, R., Romano, M., Alves, D. M., Peixoto, R., Quintela, C., Jervis, M. J., Melo, D., Pacheco, A., Paixao, V., Pedro, V., Pimenta, J., Pimenta de Castro, J., Rocha, A., Beuran, M., Ciubotaru, C., Diaconescu, B., Hostiuc, S., Negoi, I., Stoica, B., Na, N. A., Anokhin, E., Kuznetsov, G., Oganezov, G., Paramzin, F., Romanova, E., Rutkovskii, V., Shushval, M., Zabiyaka, M., Dzhumabaev, K., Ivanov, V., Mamedli, Z., Achkasov, S., Balkarov, A., Nabiev, E., Nagudov, M., Rybakov, E., Saifutdinova, K., Sushkov, O., Joseph, L., Ndayishimiye, I., Faustin, N., Mutabazi, A. 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Townson, Adam, Williams, Christopher Yee Khang, Gray, Timothy, Greig, Robert, Husain, Mansoor, Murray, Elspeth, Mustafa, Ahmed, Asif, Ashar, Gokul, Arya, Shah, Max, Akitikori, Mabel Temisanren, Charalabopoulos, Alexandros, Davidson, Sophie, McNally, Sinead, Rupani, Shamil, Juma, Fatema, Mills, Sarah Catherine, Muirhead, Laura, Sellars, Kate, Walsh, Una, Warren, Oliver, Chambers, Alice, Hunt, Richard, Boyce, Stephen, Cornwall, Hannah, Tol, Isabel, Argyriou, Eleftherios Orestis, Eardley, Nicola, Povey, Meical, Aithie, Joanna M S, Irfan, Ahmer, McGuigan, Mari-Claire, Starr, Robert, Warren, Craig Russell, Archibald, Jess, Kirby, Georgia, Kisyov, Ivan, Khoo, Chun Kheng, Lee, Rachel, Photiou, Dana, Davis, Rowan, Prasad, Uday, Yang, P Zichu, Bird, Jonathan, Leung, Edmund, Summerour, Virginia, Currow, Chelise, Kiam, Jianshen, Tan, Gerald Jack Soon, Muthusami, Anitha, Pegba-Otemolu, Ibifunke, Urbonas, Tomas, Nunoo-Mensah, Joseph, Smolskas, Edgaras, Boddy, Alex, Gravante, Gianpiero, Hunter, David, Andrew, David, Koh, Amanda, Thompson, Amari, Adams, Lawrence, Clements, Hollie A, De Silva, Kasun, Ekpete, Ogbonnia, Haque, Seraj, Henderson, Scott, Ibrahim, Bilal, Jayasinghe, Thummini, Livie, Jennifer, Mailley, Keir, Nair, Gopikrishnan, Tan, Daniel, Baggaley, Caitlin, Dawidziuk, Aleksander, Szyszka, Bartosz, Barter, Charlotte, Gandhi, Nirav, Hassell, Karen, Hitchin, Samantha, Kelsall, Jennett, Nagy, Eva, Nessa, Ashrafun, Whisker, Lisa, Yanni, Fady, Ali, Mahmoud, Arora, Deeksha, Hediwattege, Sunanda, Kumarasinghe, Navam, Rathore, Munir, Tennakoon, Athula, Ali Ahmad, Syed Mustafa, Bajomo, Oreoluwa, Nadira, Fahema, Celentano, Valerio, Griffiths, Ewen, Karri, Rama Santhosh, Mak, Jason Kei Chak, Pipe, Michelle, Bhatti, Muhammad Iqbal, Rabie, Mohamed, Boyle, Connor, Hamilton, David, Mihuna, Aishath, Ng, James Chean Khun, Nicholson, Gary, Oliwa, Agata, Pearson, Robert, Rose, Anna, Yong, Shun Qi, Boereboom, Catherine, Hanna, Michael, Walter, Catherine, Greensmith, Thomas Samuel, Mitchell, Rachel, Monaghan, Eimear, Crawford, James, Moug, Susan, Blackwell, James, Boyd-Carson, Hannah, Herrod, Philip, Al-Allaf, Omar, Beattie, Miriam, Bullock, Cameron, Burman, Shivang, Clark, Gemma, Flamey, Nicolas, Flannery, Oliver, Harding, Alexander, Kodiatt, Ben, Lawday, Samuel, Mahapatra, Shivani, Mukundu Nagesh, Navin, Ng, Michael, Rye, Dupinderjit, Yoong, Andrel, Clark, Laura, Deans, Chris, Edirisooriya, Monisha, Carrington, Emma Victoria, Wong, Tsz Lun Ernest, Yusuf, Baasil, Chamberlain, Carla, Duke, Kathryn, Kmiotek, Elizabeth, Botes, Azel, Condie, Natalie, Schrire, Timothy, Shah, Reena, Thomas-Jones, Iolo, Yates, Charlotte, Anthony, Natasha, Matthews, Edward, Sahnan, Kapil, Tankel, James, Tucker, Sally, Winter Beatty, Jasmine, Ziprin, Paul, Duggan, William, Kantartzi, Anastasia, Sridhar, Shruthi, Khaw, Rachel Alys, Srivastava, Prakhar, Underwood, Charlotte, Alves do Canto Brum, Homero, Chopra, Sharat, Davis, Laura, Hughes, Rebecca, Tulley, Joshua, Alberts, Justin, Athisayaraj, Thomas, Olugbemi, Mojolaoluwa, Ahmad, Kasim, Chan, Claudia, Chapman, Gavin, Fleming, Hannah, Fox, Benjamin, Grewar, Julia, Hulse, Kate, Rutherford, Duncan, Sinead, Mackay, Smith, Scott, Speake, Doug, Vaughan-Shaw, Peter G, Christodoulides, Natasha, Kudhail, Simrit, Welch, Matthew, Husaini, Syed Muhibullah, Lambracos, Simon, Anyanwu, Chikamuche, Suresh, Rishi, Thomas, Jimmy Scott, Gleeson, Elizabeth, Platoff, Rebecca, Saif, Areeba, Enumah, Zachary, Etchill, Eric, Gabre-Kidan, Alodia, Bernstein, Mitchell, Carrano, Francesco Maria, Connors, Joseph, Lynn, Patricio, Melis, Marcovalerio, Newman, Elliot, Foster, Deshka S, Perrone, Kenneth, Titan, Ashley, Ahmad, Sarwat, Bafford, Andrea Chao M D, Dal Molin, Marco, Hanna, Nader, Zafar, Syed Nabeel, Hemmila, Mark, Napolitano, Lena, Wong, Jane J, Chandler, Julia, Wood, Lauren, Wren, Sherry, Ottesen, Taylor, You, Lucia, Yu, Kristin, Arciénega Yañez, María Del Pilar, Ferreira Fernandes, Martin, González, Daniel, Cubas, Santiago, González, María Catalina, Zubiaurre, Vanessa, Demolin, Rodrigo, Giroff, Nicolas, Sciuto, Pablo, Campos, Maite, Rodríguez Cantera, Gabriela, Deepika, Garg, Simuchimba, Elliot, Bulaya, Anadi, Chibuye, Chali, Chirengendure, Bright, Kabale, Mary-Rose, Kabongo, Kizito, Munthali, James, Mweso, Oliver, Pikiti, Francis, Otieno, James, Lai, Log Tung, Blackman, Brighid, Richards, Sophie, Subramaniam, Suren, Karim, Rafid, Kok, Nathan, Lee, Yanni Dion, Ali, Shabina, Sinha, Aanjaneya, Corrigan, Robert, Barnes, Nicole, Wong, Florence, Dennis, Grace, Jedamzik, Julia, Phillips, Emil, Piette, Wivine, Van Hentenryck, Marie, Koco, Houenoukpo, Lawani, Souliath, Kassa, Mamo Woldu, Santos Bezerra, Tainá, Gribnev, Petar, Dimitrov, Dobromir, Krastev, Panche, Oum, Sovannarith, Bonghaseh, Divine Tim, Al Farsi, Maryam, Alsharqawi, Nourah, Acevedo, Veronica, Castillo Barbosa, Andrea Carolina, Giron, Felipe, Leon Rodriguez, Jimmy Paul, Kucan, Darko, Rosko, Damir, Barsic, Neven, Župan, Domagoj, Hegazi, Amgad, Truncíková, Vendula, Fryba, Vladimir, Mohamed, Mostafa, Sultan, Ahmed, Nagi, Ahmed, Rashad Temerik, Abdallah, Elshawy, Mohamed Elemam, Mahmoud, Moustafa Ibrahim, Omar, Shrouk, Anwar, Mohamed, Rageh, Tarek, Elmokadem, Aya, Gaballa, Khaled, Teppo, Sandra, Turunen, Antti, Pengermä, Pasi, Ballouhey, Quentin, Bergeat, Damien, Weyl, Ariane, Hain, Elisabeth, Gyedu, Adam, Yenli, Edwin, Osei-Poku, Dorcas, Rompou, Vaia-Aliki, Zoikas, Athanasios, Gaitanidis, Apostolos, Koukis, Georgios, Perivoliotis, Konstantinos, Tavlas, Panagiotis, Galanos-Demiris, Konstantinos, Zografos, George, Karavokyros, Ioannis, Xanthopoulou, Georgia, Iordanidou, Eirini, Ayau, Fernanda, Garcia, Allan, Damján, Pekli, Wason, Deepender, B L, Ashika, Rangganata, Ervandy, Kamath, Prerna, O'Connor, Donal B, Pinto, Margherita, Perrone, Fabrizio, Tropeano, Francesca Paola, Troilo, Francesca, Bossi, Daniela, Scala, Dario, Pulitanò, Lucrezia, Carella, Marcella, Pietrabissa, Andrea, Gori, Alice, Giraudo, Giorgio, De Simone, Veronica, Russo, Alfio Alessandro, Braccio, Bartolomeo, Al-Taher, Raed, Athamneh, Sarah, Parker, Andrea, Sawiee, Adnan, Kattia, Amina, Salem, Malik, Tababa, Osama, Shaeeb, Zuhour, Syminas, Vilius, Jurgaitis, Jonas, Damuleviciene, Gyte, Svagzdys, Saulius, Poskus, Tomas, Razafimanjato, Narindra Njarasoa Mihaja, Chieng Loo, Ling, Tiong, Ing Ching, Wan Muhmad, Wan Farahiyah, Vijeyan, Harinthiran, Li Ying, Teoh, Grech, Gabriella, Arrangoiz, Rodrigo, Jimenez Ley, Vania Brickelia, Arizpe, Daniel, Lagunes Lara, Elizabeth, Castro López, Elizabeth Victoria, Eaazim, Jose, Gordinou de Gouberville, Marije, Bastiaenen, Vivian, Rottier, Simone, Nahab, Fouad, Ji, Maria Yeonhee, Seyoji, Mohammed, Nwachukwu, Callistus, Emeghara, Okechukwu, Muhammed, Sayyid Egbunu, Idowu, Ayodeji, Sowemimo, Olamiposi, Ogundoyin, Olakayode, Akande, Oluwatosin, Lott, Alexander, Nadeem, Maliha, Laghari, Ahsan Ali, Loya, Asif, Mushtaq, Hassan, Abdullah, Muhammad Tariq, Abuhilal, Baseel, Atawneh, Mohammad, Hamdan, Hamdan, Alhabil, Belal, Srour, Abedelrahman, Mousa, Ibrahim, Da Silva Medina, Luis, Bartosiak, Katarzyna, Ferreira, Pedro, Francisco, Vítor, Lemos, Ricardo, Frutuoso, Luísa, Fernandes, Sara, Fonseca, Telma, Pereira, Jorge, Rachadell, Juan, Torre, Ana, Madeira Martins, Filipe, Carvalho, Ana Cristina, Rodrigues Ferreira, Joana, Ribeiro da Silva, Bruno, Devesa, Helena, Vieira, Ana, Mónica, Inês, Amaro, Margarida, Sousa, Diogo, Reia, Marta, Louro, João, Martins, Ana, Dominguez, Joaquina, Santos, Inês, Freitas Oliveira, Nuno Miguel, Pereira, José Carlos, Silva-Vaz, Pedro, Freire, Ligia, Escrevente, Ricardo, Negoita, Valentina Madalina, Shakhmatov, Dmitry, Nezerwa, Yves, Radulovic, Radosav, Obery, Gareth, Viljoen, Francois, Mendes, Tome, Suarez, Antonio, Moncada, Enrique, Fernandez-Hevia, Maria, Curtis Martínez, Carolina, Gil Garcia, Julia Maria, González Zunzarren, Mariana, Idris, Tarig, Eklöv, Karolina, Grahn, Oskar, Amin, Leila, Blomqvist, Malin, Ajani, Costanza, Kraus, Rebecca, Seeger, Nico, Willemin, Melissa, Rayya, Fadi, Ayash, Mohammad, Msouti, Raneem, Kannas, Israa, Abazid, Eias, Esper, Asil, Slim, Skander, Kavcar, Akil Serdar, Aytac, Erman, Dural, Ahmet Cem, Ilker, Ayse, Eray, Ismail Cem, Kurnaz, Eray, Altiner, Saygin, Tepe, Mustafa Deniz, Sahin, Can, Savli, Evrim, Innocent, Aryon, Babirye, Lilian, Diachenko, Andrii, Hordoskiy, Vladislav, Curry, Heather, Chau, Charlene Yat Che, Robertson, Harry, Mahmoud, Arin, Lennon, Hannah, Loi, Lynette, Kirkham, Emily, McCann, Cameron, Watts, Daniel, Gurung, Binay, Wilson, Michael, Tribedi, Thomas, Garofalo, Eleonora, Zahra, Baryab, MacDonald, Scott, Daniels, Ian, Ng, Nathan, Khosla, Shivun, Olivier, James, Yue, Sum Yu Pansy, Suresh, Gayathri, Wellington, Jack, Lorejo, Emmanuel, Mossaad, Mafdi, Crutcher, Madison, Alimi, Marjan, Baiu, Ioana, Abdou, Hossam, Conway, Alison, Peck, Connor, Perdomo Perez, Mauro Andres, Zulu, Stanley, Nakazwe, Mildred, Burger, Sule, Davies, Justine, Donaldson, Rachel, Ede, Chikwendu, Garden, O James, Lesetedi, Chiapo, Mabedi, Charles, Magill, Laura, Makinde Alakaloko, Felix, Makupe, Alex, Monahan, Mark, Mulira, Soloman, Muller, Elmi, Musowoyo, Jospeh, Olory-Togbe, Jean Léon, Roberts, Tracey, Smith, Martin, Tayler, Viki, Windsor, John, Yepez, Raul, Sundar, Sudha, Runigamugabo, Emmy, Verjee, Azmina, Chen, José, Daya, Leonid, El Aroussi, Nouhaila, Farina, Valeria, Gnintedeme Olivier, Tchianze, Gonzales Nacarino, Mauricio, Hammani, Aamr, Honjo, Sarah, Jacobs, Rebecca, Kimura, Hitomi, Nkoronko, Mugisha, Oscullo Yepez, Jasson Javier, Pin Hung, Wei, Raj, Ankit, Romani Pozo, Alina, Rommaneh, Muna, Sassamela Fabiano, Samuel Chimbioputo, Shiroma Gago, Camila Milagros, Srinivas, Abhishekh, Sung, Chia-Yen, Tai, Aswan, Valle Aranda, Yener Cristyell, Venturini, Sara, and Wilguens Lartigue, Jean

Subjects
Pediatrics, Colorectal cancer, IMPACT, Disease, Colorectal Neoplasm, 030204 cardiovascular system & hematology, Cancer, surgery, postoperative mortality, 0302 clinical medicine, Postoperative Complications, Global health, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, General Medicine, DISEASES, Income, cancer surgery, Colorectal Neoplasms, Breast Neoplasm, Cohort study, Human, Adult, Developed Countrie, medicine.medical_specialty, Global surgery, General surgery, International multicentre study, Cancer surgery, Breast Neoplasms, Department of Error, NO, Developing Countrie, 03 medical and health sciences, Breast cancer, Stomach Neoplasms, medicine, Humans, Developing Countries, Neoplasm Staging, business.industry, Developed Countries, Odds ratio, CARE, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, Prospective Studie, Postoperative Complication, business
Abstract

80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit.

Published
2021

95. Intravenous immunoglobulin therapy in COVID-19-related encephalopathy

Author

Francesca Bisulli, Caterina Tonon, Giorgia Bernabè, Sabina Cevoli, Ilaria Cani, Umberto Pensato, Gloria Stofella, Lilia Volpi, Simone Vidale, Francesca Ceccaroni, Lorenzo Ferri, Roberto Michelucci, Olivia J. Henry, Rocco Liguori, Lorenzo Muccioli, Paolo Tinuper, Giacomo Fornaro, Maria Tappatà, Elena Pasini, Pietro Cortelli, Muccioli L., Pensato U., Bernabe G., Ferri L., Tappata M., Volpi L., Cani I., Henry O.J., Ceccaroni F., Cevoli S., Stofella G., Pasini E., Fornaro G., Tonon C., Vidale S., Liguori R., Tinuper P., Michelucci R., Cortelli P., and Bisulli F.

Subjects
0301 basic medicine, Pediatrics, medicine.medical_specialty, Neurology, Constitutional symptoms, medicine.medical_treatment, Encephalopathy, Clinical Neurology, 03 medical and health sciences, 0302 clinical medicine, Intravenous Immunoglobulin Therapy, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Mechanical ventilation, IVig, Brain Diseases, Original Communication, Respiratory distress, business.industry, SARS-CoV-2, Immunoglobulins, Intravenous, medicine.disease, encephalopathy, 030104 developmental biology, Delirium, Female, Neurology (clinical), medicine.symptom, business, Covid-19, 030217 neurology & neurosurgery
Abstract

Objective To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. Methods We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. Results Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed. Conclusions Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

Published
2021

99. Esophageal Cancer : Diagnosis and Treatment

Author

Francisco Schlottmann, Lorenzo Ferri, Daniela Molena, Marco G. Patti, Francisco Schlottmann, Lorenzo Ferri, Daniela Molena, and Marco G. Patti

Subjects
Surgery, Oncology, Gastroenterology, Radiology
Abstract

This book provides comprehensive and practical guidance for the management of esophageal cancer. It presents a detailed review of the pathophysiology, clinical staging, treatment, and outcomes of patients with esophageal cancer. Chapters cover the epidemiology of the disease, latest diagnostic and staging tools, systemic therapies, and the current open and minimally invasive surgical techniques including transhiatal, Ivor Lewis and McKeown esophagectomy. Esophageal Cancer: Diagnosis and Treatment compiles experience gained across a variety of medical disciplines, with contributions from world renowned surgeons, gastroenterologists, and medical oncologists. Thanks to its multidisciplinary authorship, this book represents a unique resource for anybody who takes care of patients with esophageal cancer.

Published
2023

100. Is beta band desynchronization related to skin conductance biofeedback effectiveness in drug resistant focal epilepsy?

Author

Bruno Colombet, Christian-George Bénar, Bernard Giusiano, Fabrice Bartolomei, Francesca Pizzo, Iliana Kotwas, Lorenzo Ferri, Sophie Chen, Nicolas Roehri, University of Bologna/Università di Bologna, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), and Otten, Lisa

Subjects
0301 basic medicine, medicine.medical_specialty, Drug Resistant Epilepsy, Phase-Lag-Index, medicine.medical_treatment, Biofeedback, Audiology, Temporal lobe, 03 medical and health sciences, Beta band, Epilepsy, 0302 clinical medicine, medicine, Humans, Connectivity, medicine.diagnostic_test, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Functional connectivity, [SCCO.NEUR] Cognitive science/Neuroscience, Magnetoencephalography, Biofeedback, Psychology, medicine.disease, Phase lag, 030104 developmental biology, Neurology, Pharmaceutical Preparations, Neurology (clinical), Epilepsies, Partial, Skin conductance, business, 030217 neurology & neurosurgery
Abstract

International audience; Skin Conductance Biofeedback (SCB) is a non-invasive behavioral treatment for epilepsy based on modulation of Galvanic Skin Response (GSR). We evaluated changes in functional connectivity occurring after SCB. Six patients with drug-resistant temporal lobe epilepsy underwent monthly SCB sessions. For each patient, 10 min of resting-state magnetoencephalographic (MEG) recording were acquired before and after the first and the last SCB session. For each recording we computed the mean weighted phase lag index (WPLI) across all pair of MEG sensors. After SCB, two patients had consistent reduction of seizure frequency (>50 %). Connectivity analysis revealed a decrease of WPLI-beta band in the two responders and an increase of WPLI-alpha connectivity in all patients regardless of the clinical effect. Results suggest that reduction of WPLI-beta-low connectivity is related to the clinical response after SCB.

Published
2020

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