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11. International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape: Bertinoro Workshop, November 2022

Author

Morgagni, Paolo, Bencivenga, Maria, Carneiro, Fatima, Cascinu, Stefano, Derks, Sarah, Di Bartolomeo, Maria, Donohoe, Claire, Eveno, Clarisse, Gisbertz, Suzanne, Grimminger, Peter, Gockel, Ines, Grabsch, Heike, Kassab, Paulo, Langer, Rupert, Lonardi, Sara, Maltoni, Marco, Markar, Sheraz, Moehler, Markus, Marrelli, Daniele, Mazzei, Maria Antonietta, Melisi, Davide, Milandri, Carlo, Moenig, Paul Stefan, Mostert, Bianca, Mura, Gianni, Polkowski, Wojciech, Reynolds, John, Saragoni, Luca, Van Berge Henegouwen, Mark I., Van Hillegersberg, Richard, Vieth, Michael, Verlato, Giuseppe, Torroni, Lorena, Wijnhoven, Bas, Tiberio, Guido Alberto Massimo, Yang, Han-Kwang, Roviello, Franco, and de Manzoni, Giovanni

Published
2024
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13. Predicting Thermoelectric Power Factor of Bismuth Telluride During Laser Powder Bed Fusion Additive Manufacturing

Author

Agarwal, Ankita, Banerjee, Tanvi, Gockel, Joy, LeBlanc, Saniya, Walker, Joe, and Middendorf, John

Subjects
Computer Science - Machine Learning, Computer Science - Computational Engineering, Finance, and Science
Abstract

An additive manufacturing (AM) process, like laser powder bed fusion, allows for the fabrication of objects by spreading and melting powder in layers until a freeform part shape is created. In order to improve the properties of the material involved in the AM process, it is important to predict the material characterization property as a function of the processing conditions. In thermoelectric materials, the power factor is a measure of how efficiently the material can convert heat to electricity. While earlier works have predicted the material characterization properties of different thermoelectric materials using various techniques, implementation of machine learning models to predict the power factor of bismuth telluride (Bi2Te3) during the AM process has not been explored. This is important as Bi2Te3 is a standard material for low temperature applications. Thus, we used data about manufacturing processing parameters involved and in-situ sensor monitoring data collected during AM of Bi2Te3, to train different machine learning models in order to predict its thermoelectric power factor. We implemented supervised machine learning techniques using 80% training and 20% test data and further used the permutation feature importance method to identify important processing parameters and in-situ sensor features which were best at predicting power factor of the material. Ensemble-based methods like random forest, AdaBoost classifier, and bagging classifier performed the best in predicting power factor with the highest accuracy of 90% achieved by the bagging classifier model. Additionally, we found the top 15 processing parameters and in-situ sensor features to characterize the material manufacturing property like power factor. These features could further be optimized to maximize power factor of the thermoelectric material and improve the quality of the products built using this material., Comment: 8 pages, 2 figures, 2 tables, accepted at Data Science for Smart Manufacturing and Healthcare workshop (DS2-MH) at SIAM International Conference on Data Mining (SDM23) conference

Published
2023

14. Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat

Author

Tamara Zenz, Robert Jenke, Denys Oliinyk, Sandra Noske, René Thieme, Tim Kahl, Ines Gockel, Florian Meier-Rosar, Achim Aigner, and Thomas RH Büch

Subjects
Gastric cancer, Entinostat, EGFR, Amphiregulin, Histone deacetylases, HDAC inhibition, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Histone deacetylase inhibitors (HDACi) have shown promising preclinical activity in gastric cancer cells; unfortunately, however, these could not be confirmed in clinical trials. This highlights the need for the identification of underlying reasons, which may also provide the basis for possible combination therapies. Here, we delineated the effects of HDACi on components of EGFR signalling in gastric cancer cells. Methods: We investigated entinostat effects on EGFR and amphiregulin (AREG) expression in various cell line- and primary patient tumor-based in vitro, ex vivo and in vivo models, on the mRNA and protein level. Based on these results, a combined entinostat plus EGFR inhibitor erlotinib treatment in vitro and in vivo was studied. Results: Proteomics analyses in gastric cancer cells treated with entinostat revealed a marked upregulation of EGFR in the majority of cell lines and an even more robust induction of the EGFR ligand AREG. This was confirmed in a panel of different cell lines in vitro, in tumor tissue-slice cultures ex vivo and in cell line- or patient-derived tumor xenografts in mice. Since previous studies in other tumor entities showed a downregulation of EGFR by HDACi, our findings thus indicate essential differences in the adaptive response of gastric carcinoma cells. Moreover, our results provided the basis for combined entinostat + EGFR inhibitor (erlotinib) treatment, and indeed we demonstrate synergistic effects in combination therapy studies. Conclusion: Our findings establish the profound upregulation of the EGFR/AREG axis by entinostat as starting point for a rational combination therapy in gastric carcinoma.

Published
2025
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15. Correction: International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape

Author

Morgagni, Paolo, Bencivenga, Maria, Carneiro, Fatima, Cascinu, Stefano, Derks, Sarah, Di Bartolomeo, Maria, Donohoe, Claire, Eveno, Clarisse, Gisbertz, Suzanne, Grimminger, Peter, Gockel, Ines, Grabsch, Heike, Kassab, Paulo, Langer, Rupert, Lonardi, Sara, Maltoni, Marco, Markar, Sheraz, Moehler, Markus, Marrelli, Daniele, Mazzei, Maria Antonietta, Melisi, Davide, Milandri, Carlo, Moenig, Paul Stefan, Mostert, Bianca, Mura, Gianni, Polkowski, Wojciech, Reynolds, John, Saragoni, Luca, Van Berge Henegouwen, Mark I., Van Hillegersberg, Richard, Vieth, Michael, Verlato, Giuseppe, Torroni, Lorena, Wijnhoven, Bas, Tiberio, Guido Alberto Massimo, Yang, Han-Kwang, Roviello, Franco, and de Manzoni, Giovanni

Published
2024
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17. Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions

Author

Lindström, Sara, Wang, Lu, Feng, Helian, Majumdar, Arunabha, Huo, Sijia, Macdonald, James, Harrison, Tabitha, Turman, Constance, Chen, Hongjie, Mancuso, Nicholas, Bammler, Theo, Consortium, Breast Cancer Association, Gallinger, Steve, Gruber, Stephen B, Gunter, Marc J, Le Marchand, Loic, Moreno, Victor, Offit, Kenneth, Study, Genetics And Epidemiology Of Colorectal Cancer Consortium Colorectal Transdisciplinary Study Colon Cancer Family Registry, De Vivo, Immaculata, O’Mara, Tracy A, Spurdle, Amanda B, Tomlinson, Ian, Consortium, Endometrial Cancer Association, Fitzgerald, Rebecca, Gharahkhani, Puya, Gockel, Ines, Jankowski, Janusz, Macgregor, Stuart, Schumacher, Johannes, Barnholtz-Sloan, Jill, Bondy, Melissa L, Houlston, Richard S, Jenkins, Robert B, Melin, Beatrice, Wrensch, Margaret, Brennan, Paul, Christiani, David C, Johansson, Mattias, Mckay, James, Aldrich, Melinda C, Amos, Christopher I, Landi, Maria Teresa, Tardon, Adonina, Consortium, International Lung Cancer, Bishop, D Timothy, Demenais, Florence, Goldstein, Alisa M, Iles, Mark M, Kanetsky, Peter A, Law, Matthew H, Consortium, Ovarian Cancer Association, Amundadottir, Laufey T, Stolzenberg-Solomon, Rachael, Wolpin, Brian M, Consortium, Pancreatic Cancer Cohort, Klein, Alison, Petersen, Gloria, Risch, Harvey, Consortium, The PRACTICAL Consortium Pancreatic Cancer Case-Control, Chanock, Stephen J, Purdue, Mark P, Scelo, Ghislaine, Pharoah, Paul, Kar, Siddhartha, Hung, Rayjean J, Pasaniuc, Bogdan, and Kraft, Peter

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Digestive Diseases, Women's Health, Prevention, Cancer, Cancer Genomics, Human Genome, Rare Diseases, 2.1 Biological and endogenous factors, Male, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Neoplasms, Risk Factors, Transcriptome, Polymorphism, Single Nucleotide, Breast Cancer Association Consortium, Colorectal Transdisciplinary Study (CORECT), Colon Cancer Family Registry Study (CCFR), Genetics And Epidemiology Of Colorectal Cancer Consortium, Endometrial Cancer Association Consortium, International Lung Cancer Consortium, Ovarian Cancer Association Consortium, Pancreatic Cancer Cohort Consortium, Pancreatic Cancer Case-Control Consortium (Panc4), The PRACTICAL Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.MethodsWe collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.ResultsWe observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci.ConclusionsOverall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.

Published
2023

19. Kolonkarzinom

Author

Mehdorn, Matthias, Kobitzsch, Benjamin, Rabe, Sebastian Murad, Gockel, Ines, and Stelzner, Sigmar

Published
2024
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23. Biologically targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett’s esophagus and esophageal adenocarcinoma

Author

Li Yan, Qianchuan He, Shiv P. Verma, Xu Zhang, Ann-Sophie Giel, Carlo Maj, Kathryn Graz, Elnaz Naderi, Jianhong Chen, Mourad Wagdy Ali, Puya Gharahkhani, Xiang Shu, Kenneth Offit, Pari M. Shah, Hans Gerdes, Daniela Molena, Amitabh Srivastava, Stuart MacGregor, Claire Palles, René Thieme, Michael Vieth, Ines Gockel, Thomas L. Vaughan, Johannes Schumacher, and Matthew F. Buas

Subjects
gene-gene interaction, post-GWAS, knowledge-guided filtering, machine learning, large scale computing, Barrett’s esophagus, Genetics, QH426-470
Abstract

Summary: Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett’s esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (1) known/plausible links to BE/EAC pathogenesis (n = 493) or (2) prior evidence of biological interactions (n = 4,196). Approximately 75 × 106 SNP×SNP interactions were screened via hierarchical group lasso (glinternet) using BEACON GWAS data. The top ∼2,000 interactions retained in each scan were prioritized using p values from single logistic models. Identical scans were repeated among males only (78%), with two independent GWAS datasets used for replication. In overall and male-specific primary replications, 11 of 187 and 20 of 191 interactions satisfied p

Published
2025
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26. Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy

Author

Nickel, F., Studier-Fischer, A., Özdemir, B., Odenthal, J., Müller, L.R., Knoedler, S., Kowalewski, K.F., Camplisson, I., Allers, M.M., Dietrich, M., Schmidt, K., Salg, G.A., Kenngott, H.G., Billeter, A.T., Gockel, I., Sagiv, C., Hadar, O.E., Gildenblat, J., Ayala, L., Seidlitz, S., Maier-Hein, L., and Müller-Stich, B.P.

Published
2025
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27. Consensus Statement on the Use of Near-Infrared Fluorescence Imaging during Pancreatic Cancer Surgery Based on a Delphi Study: Surgeons’ Perspectives on Current Use and Future Recommendations

Author

de Muynck, Lysanne DAN, White, Kevin P, Alseidi, Adnan, Bannone, Elisa, Boni, Luigi, Bouvet, Michael, Falconi, Massimo, Fuchs, Hans F, Ghadimi, Michael, Gockel, Ines, Hackert, Thilo, Ishizawa, Takeaki, Kang, Chang Moo, Kokudo, Norihiro, Nickel, Felix, Partelli, Stefano, Rangelova, Elena, Swijnenburg, Rutger Jan, Dip, Fernando, Rosenthal, Raul J, Vahrmeijer, Alexander L, and Mieog, J Sven D

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pancreatic Cancer, Rare Diseases, Cancer, Digestive Diseases, fluorescence-guided surgery, intraoperative imaging, pancreatic cancer, cancer surgery, near-infrared fluorescence, indocyanine green, consensus, Delphi, Oncology and carcinogenesis
Abstract

Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons' perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with ≥70% agreement considered consensus and ≥80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS's benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS's use during PDAC surgery.

Published
2023

29. An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer

Author

Cizmic, Amila, Romic, Ivan, Balla, Andrea, Barabino, Nicolò, Anania, Gabriele, Baiocchi, Gian Luca, Bakula, Branko, Balagué, Carmen, Berlth, Felix, Bintintan, Vasile, Bracale, Umberto, Egberts, Jan-Hendrik, Fuchs, Hans F., Gisbertz, Suzanne S., Gockel, Ines, Grimminger, Peter, van Hillegersberg, Richard, Inaki, Noriyuki, Immanuel, Arul, Korr, Daniel, Lingohr, Philipp, Mascagni, Pietro, Melling, Nathaniel, Milone, Marco, Mintz, Yoav, Morales-Conde, Salvador, Moulla, Yusef, Müller-Stich, Beat P., Nakajima, Kiyokazu, Nilsson, Magnus, Reeh, Matthias, Sileri, Pierpaolo, Targarona, Eduardo M., Ushimaru, Yuki, Kim, Young-Woo, Markar, Sheraz, Nickel, Felix, and Mitra, Anuja T.

Published
2024
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35. Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial

Author

Ala-Kokko, Tero, Gockel, Maarit, Haapanen, Susanna, Haukipää, Mia, Lehtonen, Sanna, Nieminen, Eeva-Maija, Niskanen, Joni, Oksi, Jarmo, Otava, Ulla, Rutanen, Taija, Salmela, Petri, Savolainen, Joni, Tuominen, Susanna, Vartiainen, Henri, Ylä-Outinen, Heli, Halme, Alex L.E., Laakkonen, Sanna, Rutanen, Jarno, Nevalainen, Olli P.O., Sinisalo, Marjatta, Horstia, Saana, Mustonen, Jussi M.J., Pourjamal, Negar, Vanhanen, Aija, Rosberg, Tuomas, Renner, Andreas, Perola, Markus, Paukkeri, Erja-Leena, Patovirta, Riitta-Liisa, Parkkila, Seppo, Paajanen, Juuso, Nykänen, Taina, Mäntylä, Jarkko, Myllärniemi, Marjukka, Mattila, Tiina, Leinonen, Maarit K., Külmäsu, Alvar, Kuutti, Pauliina, Kuitunen, Ilari, Kreivi, Hanna-Riikka, Kilpeläinen, Tuomas P., Kauma, Heikki, Kalliala, Ilkka E.J., Järvinen, Petrus, Hankkio, Riina, Hammarén, Taina, Feuth, Thijs, Ansakorpi, Hanna, Ala-Karvia, Riikka, Guyatt, Gordon H., and Tikkinen, Kari A.O.

Published
2024
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36. The Aftermath – What Future for African Studies (in Europe?). A View From Behind the Scenes of ECAS9

Author

Steven van Wolputte, Michael Thomas Bollig, Martina Gockel, Clemens Greiner, and Noah Kahindi

Subjects
History of Africa, DT1-3415, International relations, JZ2-6530, Social Sciences
Abstract

In the spring of 2023, the ninth European Conference on African Studies (ECAS) took place in Cologne. Though not unexpected (or unusual) this event sparked critical comments and questions. As the organisers, we understand and appreciate this criticism. We, therefore, felt the need to respond to at least some of them, partly because we also asked ourselves many of these questions before, during, and after the conference. At the same time, we want to call for a certain degree of pragmatism when it comes to organising an event this size by providing a look behind the scenes.

Published
2024
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37. Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation

Author

Víctor Urbiola-Salvador, Agnieszka Jabłońska, Dominika Miroszewska, Weronika Kamysz, Katarzyna Duzowska, Kinga Drężek-Chyła, Ronny Baber, René Thieme, Ines Gockel, Marek Zdrenka, Ewa Śrutek, Łukasz Szylberg, Michał Jankowski, Dariusz Bała, Wojciech Zegarski, Tomasz Nowikiewicz, Wojciech Makarewicz, Agnieszka Adamczyk, Aleksandra Ambicka, Marcin Przewoźnik, Agnieszka Harazin-Lechowska, Janusz Ryś, Katarzyna Macur, Paulina Czaplewska, Natalia Filipowicz, Arkadiusz Piotrowski, Jan P Dumanski, and Zhi Chen

Subjects
Medicine (General), R5-920
Abstract

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

Published
2024
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38. Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker

Author

Patrick S. Plum, Timo Hess, Denis Bertrand, Isabelle Morgenstern, Oscar Velazquez Camacho, Christoph Jonas, Christina Alidousty, Britta Wagner, Stephanie Roessler, Thomas Albrecht, Jessica Becker, Vanessa Richartz, Barbara Holz, Sascha Hoppe, Huay Mei Poh, Burton Kuan Hui Chia, Cheryl Xueli Chan, Thushangi Pathiraja, Audrey SM Teo, Jens U. Marquardt, Alexis Khng, Michael Heise, Yao Fei, René Thieme, Sebastian Klein, Jing Han Hong, Simona O Dima, Irinel Popescu, Maria Hoppe‐Lotichius, Reinhard Buettner, Anja Lautem, Gerd Otto, Alexander Quaas, Niranjan Nagarajan, Steve Rozen, Bin Tean Teh, Benjamin Goeppert, Uta Drebber, Hauke Lang, Patrick Tan, Ines Gockel, Johannes Schumacher, and Axel M. Hillmer

Subjects
fusion genes, genomics, intrahepatic cholangiocarcinoma, PBX1, transcriptomics, Medicine (General), R5-920
Abstract

Abstract Background Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease. Methods We describe an integrated whole‐exome sequencing and transcriptomic study of 37 iCCAs patients in Germany. Results We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke‐associated Asian iCCAs. Conclusions By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease.

Published
2024
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39. A Creative Medical Investigation: Bridging the Soft Skill Gap

Author

Wood, Tyler A., Grahovec, Nicholas E., Sanfilippo, Catrina M., Hill, Christopher, and Gockel-Blessing, Elizabeth A.

Abstract

The refinement of soft skills is essential to the success of athletic training students. Yet, more work is needed to identify desirable educational techniques to support the progression of soft skills in athletic training education. The current study identified professional athletic training students' (10 students; 21.2 ± 2.1 years) perceptions of the five-part creative medical investigation (CMI) and described how the CMI could contribute to clinical reasoning, collaboration, and reflection, along with integrating soft skills with hard skills. The consensual qualitative research (CQR) approach utilized semi-structured interviews after the five CMI parts. Three qualitative researchers conducted CQR analysis after all interviews were complete. The researchers independently coded the interview transcripts and met to triangulate common themes; member checks were conducted to validate the findings. A 10-month follow-up survey evaluated the long-term effects of the CMI on selected subdomains of clinical reasoning. Five themes were identified from the consensual qualitative analysis. This CMI (1) Facilitated clinical reasoning, (2) Encouraged collaboration and reflection, (3) Promoted soft and hard skill integration, (4) Improved student confidence, (5) Enjoyed by the students. The follow-up survey indicated that students agreed (4.1-4.5 out of 5) this CMI leads to improvement in clinical reasoning subdomains. The current CMI facilitated desirable soft skills and integrated soft skills with hard skills through an enjoyable experience. Thus, the CMI might be a desirable educational technique with long-term implications to support the progression of soft skills in health care education.

Published
2023
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40. Visceral obesity determined in routine preoperative CT scans predicts risk of postoperative burst abdomen

Author

Matthias Mehdorn, Benedikt Schnarkowski, Yusef Moulla, Johanna Pape, Timm Denecke, Ines Gockel, Woubet Tefera Kassahun, and Hans-Jonas Meyer

Subjects
Medicine, Science
Abstract

Abstract Burst abdomen (BA) remains a severe postoperative complication after abdominal surgery. Obesity is a known risk factor for postoperative complications but objective parameters such as body mass index fail to predict BA after abdominal surgery. In recent literature, CT-derived body composition assessment could predict obesity-related diseases and surgical site infections. We report data from the institutional wound register, comparing patients with BA to a subgroup of patients without BA. The CT images were evaluated for intraabdominal and subcutaneous fat tissues. Univariate and multivariate risk factor analysis was performed in order to evaluate CT-derived obesity parameters as risk factor for BA. 92 patients with BA were compared to 32 controls. Patients with BA had significantly more visceral obesity (VO; p

Published
2023
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41. Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers

Author

Anja Seckinger, Sara Majocchi, Valéry Moine, Lise Nouveau, Hoang Ngoc, Bruno Daubeuf, Ulla Ravn, Nicolas Pleche, Sebastien Calloud, Lucile Broyer, Laura Cons, Adeline Lesnier, Laurence Chatel, Anne Papaioannou, Susana Salgado-Pires, Sebastian Krämer, Ines Gockel, Florian Lordick, Krzysztof Masternak, Yves Poitevin, Giovanni Magistrelli, Pauline Malinge, Limin Shang, Sonja Kallendrusch, Klaus Strein, and Dirk Hose

Subjects
Bispecific antibody, CD3, CEACAM5, Immunotherapy, T-cell engager, Solid cancer, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA). Methods We present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format). Results NILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the “LALAPA” mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (E max = 89%), MKN-45 (E max = 84%), and H2122 (E max = 97%), with EC50 ranging from 0.02 to 0.14 nM. NILK-2301 binds neither to CEACAM5-negative or primary colon epithelial cells nor to other CEACAM family members. NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models. In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model. Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg intravenously or 20 mg subcutaneously showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days. NILK-2301 was well-tolerated. Data were confirmed in human FcRn TG32 mice. Conclusions In summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.

Published
2023
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48. Standardizing eligibility and patient selection for Pressurized Intraperitoneal Aerosol Chemotherapy: A Delphi consensus statement

Author

Afifi, Adnane, Alyami, Mohammad, Mortensen, Michael Bau, Bhatt, Aditi, Brandl, Andreas, Brigand, Cécile, Casella, Francesco, Chia, Claramae Shulyn, Coget, Julien, Delgadillo, Xavier, Dellinger, Thanh, Di Giorgio, Andrea, Escayola, Cecilia, Ezanno, Anne-Cécile, Geboes, Karen, Giger-Pabst, Urs, Gockel, Ines, Graversen, Martin, Jäger, Tarkan, Jones, Sadie, Katdare, Ninad, Kepenekian, Vahan, Khomiakov, Vladimir, Kothonidis, Konstantinos, Lavoue, Vincent, Lehmann, Kuno, Lordick, Florian, Lynch, Craig, Mulier, Stefaan, Paquette, Brice, Yong, Wei Peng, Prenen, Hans, Raoof, Mustafa, Rau, Beat, Ris, Frederic, Robella, Manuela, Somashekhar, Sampige Prasanna, Sourrouille, Isabelle, Steffen, Thomas, Sundar, Raghav, Thieme, René, Torkington, Jared, Ukegjini, Kristjan, Van der Speeten, Kurt, Villeneuve, Laurent, Tozzi, Francesca, Rashidian, Nikdokht, Ceelen, Wim, Callebout, Eduard, Hübner, Martin, Sgarbura, Olivia, and Willaert, Wouter

Published
2024
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49. Predictors of anastomotic leak and conduit necrosis after oesophagectomy: Results from the oesophago-gastric anastomosis audit (OGAA)

Author

Halle-Smith, J.M., Kamarajah, S.K., Evans, R.P.T., Nepogodiev, D., Hodson, J., Bundred, J.R., Gockel, I., Gossage, J.A., Isik, A., Kauppila, J.H., Kidane, B., Mahendran, H.A., Negoi, I., Okonta, K.E., Sayyed, R., van Hillegersberg, R., Vohra, R.S., Wijnhoven, B.P.L., Singh, P., Griffiths, E.A., Alderson, D., Bundred, J., Gossage, J., Jefferies, B., McKay, S., Mohamed, I., Siaw- Acheampong, K., Vohra, R., Wanigasooriya, K., Whitehouse, T., Gjata, A., Moreno, J.I., Takeda, F.R., Guevara Castro, R., Bekele, A., Harustiak, T., Kechagias, A., Bagajevas, A., Kennedy, A., Da Roit, A., Azagra, J.S., Mejía-Fernández, L., El Kafsi, J., Sayyed, R.H., Sousa, M., Sampaio, A.S., Blanco, R., Wallner, B., Schneider, P.M., Hsu, P.K., Gananadha, S., Wills, V., Devadas, M., Duong, C., Talbot, M., Hii, M.W., Jacobs, R., Andreollo, N.A., Johnston, B., Darling, G., Isaza-Restrepo, A., Rosero, G., Arias- Amézquita, F., Raptis, D., Gaedcke, J., Reim, D., Izbicki, J., Egberts, J.H., Dikinis, S., Kjaer, D.W., Larsen, M.H., Achiam, M.P., Saarnio, J., Theodorou, D., Liakakos, T., Korkolis, D.P., Robb, W.B., Collins, C., Murphy, T., Reynolds, J., Tonini, V., Migliore, M., Bonavina, L., Valmasoni, M., Bardini, R., Weindelmayer, J., Terashima, M., White, R.E., Alghunaim, E., Elhadi, M., Leon-Takahashi, A.M., Medina-Franco, H., Lau, P.C., Heisterkamp, J., Rosman, C., Beban, G., Babor, R., Gordon, A., Rossaak, J.I., Pal, K.M.I., Qureshi, A.U., Naqi, S.A., Syed, A.A., Barbosa, J., Vicente, C.S., Leite, J., Freire, J., Casaca, R., Costa, R.C.T., Scurtu, R.R., Mogoanta, S.S., Bolca, C., Constantinoiu, S., Sekhniaidze, D., Bjelović, M., So, J.B.Y., Gačevski, G., Loureiro, C., Pera, M., Bianchi, A., Moreno Gijón, M., Martín Fernández, J., Trugeda Carrera, M.S., Vallve-Bernal, M., Cítores Pascual, M.A., Elmahi, S., Halldestam, I., Hedberg, J., Mönig, S., Gutknecht, S., Tez, M., Guner, A., Tirnaksiz, M.B., Colak, E., Sevinç, B., Hindmarsh, A., Khan, I., Khoo, D., Byrom, R., Gokhale, J., Wilkerson, P., Jain, P., Chan, D., Robertson, K., Iftikhar, S., Skipworth, R., Forshaw, M., Higgs, S., Nijjar, R., Viswanath, Y.K.S., Turner, P., Dexter, S., Boddy, A., Allum, W.H., Oglesby, S., Cheong, E., Beardsmore, D., Maynard, N., Berrisford, R., Mercer, S., Puig, S., Melhado, R., Kelty, C., Underwood, T., Dawas, K., Lewis, W., Al-Bahrani, A., Bryce, G., Thomas, M., Arndt, A.T., Palazzo, F., Meguid, R.A., Fergusson, J., Beenen, E., Mosse, C., Salim, J., Cheah, S., Wright, T., Cerdeira, M.P., McQuillan, P., Richardson, M., Liem, H., Spillane, J., Yacob, M., Albadawi, F., Thorpe, T., Dingle, A., Cabalag, C., Loi, K., Fisher, O.M., Ward, S., Read, M., Johnson, M., Bassari, R., Bui, H., Cecconello, I., Sallum, R.A.A., da Rocha, J.R.M., Lopes, L.R., Tercioti, V., Coelho, J.D.S., Ferrer, J.A.P., Buduhan, G., Tan, L., Srinathan, S., Shea, P., Yeung, J., Allison, F., Carroll, P., Vargas-Barato, F., Gonzalez, F., Ortega, J., Nino-Torres, L., Beltrán-García, T.C., Castilla, L., Pineda, M., Bastidas, A., Gómez-Mayorga, J., Cortés, N., Cetares, C., Caceres, S., Duarte, S., Pazdro, A., Snajdauf, M., Faltova, H., Sevcikova, M., Mortensen, P.B., Katballe, N., Ingemann, T., Morten, B., Kruhlikava, I., Ainswort, A.P., Stilling, N.M., Eckardt, J., Holm, J., Thorsteinsson, M., Siemsen, M., Brandt, B., Nega, B., Teferra, E., Tizazu, A., Koivukangas, V., Meriläinen, S., Gruetzmann, R., Krautz, C., Weber, G., Golcher, H., Emons, G., Azizian, A., Ebeling, M., Niebisch, S., Kreuser, N., Albanese, G., Hesse, J., Volovnik, L., Boecher, U., Reeh, M., Triantafyllou, S., Schizas, D., Michalinos, A., Balli, E., Mpoura, M., Charalabopoulos, A., Manatakis, D.K., Balalis, D., Bolger, J., Baban, C., Mastrosimone, A., McAnena, O., Quinn, A., Ó Súilleabháin, C.B., Hennessy, M.M., Ivanovski, I., Khizer, H., Ravi, N., Donlon, N., Cervellera, M., Vaccari, S., Bianchini, S., Sartarelli, l, Asti, E., Bernardi, D., Merigliano, S., Provenzano, L., Scarpa, M., Saadeh, L., Salmaso, B., De Manzoni, G., Giacopuzzi, S., La Mendola, R., De Pasqual, C.A., Tsubosa, Y., Niihara, M., Irino, T., Makuuchi, R., Ishii, K., Mwachiro, M., Fekadu, A., Odera, A., Mwachiro, E., AlShehab, D., Ahmed, H.A., Shebani, A.O., Elhadi, A., Elnagar, F.A., Elnagar, H.F., Makkai-Popa, S.T., Wong, L.F., Yr, Tan, S, Thannimalai, Ca, Ho, Ws, Pang, Jh, Tan, Hnl, Basave, Cortés-González, R., Lagarde, S.M., van Lanschot, J.J.B., Cords, C., Jansen, W.A., Martijnse, I., Matthijsen, R., Bouwense, S., Klarenbeek, B., Verstegen, M., van Workum, F., Ruurda, J.P., van der Sluis, P.C., de Maat, M., Evenett, N., Johnston, P., Patel, R., MacCormick, A., Young, M., Smith, B., Ekwunife, C., Memon, A.H., Shaikh, K., Wajid, A., Khalil, N., Haris, M., Mirza, Z.U., Qudus, S.B.A., Sarwar, M.Z., Shehzadi, A., Raza, A., Jhanzaib, M.H., Farmanali, J., Zakir, Z., Shakeel, O., Nasir, I., Khattak, S., Baig, M., Noor, M.A., Ahmed, H.H., Naeem, A., Pinho, A.C., da Silva, R., Bernardes, A., Campos, J.C., Matos, H., Braga, T., Monteiro, C., Ramos, P., Cabral, F., Gomes, M.P., Martins, P.C., Correia, A.M., Videira, J.F., Ciuce, C., Drasovean, R., Apostu, R., Paitici, S., Racu, A.E., Obleaga, C.V., Beuran, M., Stoica, B., Ciubotaru, C., Negoita, V., Cordos, I., Birla, R.D., Predescu, D., Hoara, P.A., Tomsa, R., Shneider, V., Agasiev, M., Ganjara, I., Gunjić, D., Veselinović, M., Babič, T., Chin, T.S., Shabbir, A., Kim, G., Crnjac, A., Samo, H., Díez del Val, I., Leturio, S., Ramón, J.M., Dal Cero, M., Rifá, S., Rico, M., Pagan Pomar, A., Martinez Corcoles, J.A., Rodicio Miravalles, J.L., Pais, S.A., Turienzo, S.A., Alvarez, L.S., Campos, P.V., Rendo, A.G., García, S.S., Santos, E.P.G., Martínez, E.T., Fernández Díaz, M.J., Magadán Álvarez, C., Concepción Martín, V., Díaz López, C., Rosat Rodrigo, A., Pérez Sánchez, L.E., Bailón Cuadrado, M., Tinoco Carrasco, C., Choolani Bhojwani, E., Sánchez, D.P., Ahmed, M.E., Dzhendov, T., Lindberg, F., Rutegård, M., Sundbom, M., Mickael, C., Colucci, N., Schnider, A., Er, S., Kurnaz, E., Turkyilmaz, S., Turkyilmaz, A., Yildirim, R., Baki, B.E., Akkapulu, N., Karahan, O., Damburaci, N., Hardwick, R., Safranek, P., Sujendran, V., Bennett, J., Afzal, Z., Shrotri, M., Chan, B., Exarchou, K., Gilbert, T., Amalesh, T., Mukherjee, D., Mukherjee, S., Wiggins, T.H., Kennedy, R., McCain, S., Harris, A., Dobson, G., Davies, N., Wilson, I., Mayo, D., Bennett, D., Young, R., Manby, P., Blencowe, N., Schiller, M., Byrne, B., Mitton, D., Wong, V., Elshaer, A., Cowen, M., Menon, V., Tan, L.C., McLaughlin, E., Koshy, R., Sharp, C., Brewer, H., Das, N., Cox, M., Al Khyatt, W., Worku, D., Iqbal, R., Walls, L., McGregor, R., Fullarton, G., Macdonald, A., MacKay, C., Craig, C., Dwerryhouse, S., Hornby, S., Jaunoo, S., Wadley, M., Baker, C., Saad, M., Kelly, M., Davies, A., Di Maggio, F., Mistry, P., Singhal, R., Tucker, O., Kapoulas, S., Powell-Brett, S., Davis, P., Bromley, G., Watson, L., Verma, R., Ward, J., Shetty, V., Ball, C., Pursnani, K., Sarela, A., Sue Ling, H., Mehta, S., Hayden, J., To, N., Palser, T., Hunter, D., Supramaniam, K., Butt, Z., Ahmed, A., Kumar, S., Chaudry, A., Moussa, O., Kordzadeh, A., Lorenzi, B., Wilson, M., Patil, P., Noaman, I., Willem, J., Bouras, G., Evans, R., Singh, M., Warrilow, H., Ahmad, A., Tewari, N., Yanni, F., Couch, J., Theophilidou, E., Reilly, J.J., van Boxel, Gijs, Akbari, K., Zanotti, D., Sgromo, B., Sanders, G., Wheatley, T., Ariyarathenam, A., Reece-Smith, A., Humphreys, L., Choh, C., Carter, N., Knight, B., Pucher, P., Athanasiou, A., Tan, B., Abdulrahman, M., Vickers, J., Akhtar, K., Chaparala, R., Brown, R., Alasmar, M.M.A., Ackroyd, R., Patel, K., Tamhankar, A., Wyman, A., Walker, R., Grace, B., Abbassi, N., Slim, N., Ioannidi, L., Blackshaw, G., Havard, T., Escofet, X., Powell, A., Owera, A., Rashid, F., Jambulingam, P., Padickakudi, J., Ben-Younes, H., Mccormack, K., Makey, I.A., Karush, M.K., Seder, C.W., Liptay, M.J., Chmielewski, G., Rosato, E.L., Berger, A.C., Zheng, R., Okolo, E., Singh, A., Scott, C.D., Weyant, M.J., Mitchell, J.D., and Griffiths, Ewen A.

Published
2024
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50. European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

Author

Kroese, Tiuri E., Bronzwaer, Sebastiaan, van Rossum, Peter S.N., Schoppman, Sebastian F., Deseyne, Pieter R.A.J., van Cutsem, Eric, Haustermans, Karin, Nafteux, Philippe, Thomas, Melissa, Obermannova, Radka, Mortensen, Hanna R., Nordsmark, Marianne, Pfeiffer, Per, Elme, Anneli, Adenis, Antoine, Piessen, Guillaume, Bruns, Christiane J., Lordick, Florian, Gockel, Ines, Moehler, Markus, Gani, Cihan, Liakakos, Theodore, Reynolds, John V., Morganti, Alessio G., Rosati, Riccardo, Castoro, Carlo, Cellini, Francesco, D'Ugo, Domenico, Roviello, Franco, Bencivenga, Maria, de Manzoni, Giovanni, van Berge Henegouwen, Mark I., Hulshoff, Maarten C.C.M, van Dieren, Jolanda, Vollebergh, Marieke, van Sandick, Johanna W., Jeene, Paul, Muijs, Christel, Slingerland, Marije, Voncken, Francine E.M., Hartgrink, Henk, Creemers, Geert-Jan, van der Sangen, Maurice J.C., Nieuwenhuijzen, Grard A.P., Berbee, Maaike, Verheij, Marcel, Wijnhoven, Bas, Beerepoot, Laurens V., Mohammad, Nadia Haj, Mook, Stella, Ruurda, Jelle P., Kolodziejczyk, Piotr, Polkowski, Wojciech P., Wyrwicz, Lucjan, Alsina, Maria, Tabernero, Josep, Pera, Manuel, Kanonnikoff, Tania F., Cervantes, Andrés, Nilsson, Magnus, Monig, Stefan, Wagner, Anna D., Guckenberger, Matthias, Griffiths, Ewen A., Smyth, Elizabeth, Hanna, George B., Markar, Sheraz, Chaudry, M. Asif, Hawkins, Maria A., Cheong, Edward, van Laarhoven, Hanneke W.M., and van Hillegersberg, Richard

Published
2024
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