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2. Targeting T cells with tetravalent bispecific antibodies for the treatment of graft-versus-host disease

Author

Madelyn Espinosa-Cotton, Sayed Shahabuddin Hoseini, Ileana C. Miranda, John Herrick, and Nai-Kong V. Cheung

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Allogeneic hematopoietic stem cell transplantation is an established treatment for hematological malignancies and some genetic diseases. Acute graft-versus-host disease (GVHD) is the most common and debilitating side effect with poor survival rates of 5% to 30% for severe cases. In this manuscript, we describe a tetravalent T-cell–engaging bispecific antibody (BsAb) based on the immunoglobulin G-[L]-single-chain variable fragment (IgG-[L]-scFv) platform, with all 4 binding domains specific for CD3. In vitro, picomolar concentrations of the CD3×CD3 BsAb induced potent lysis of activated CD4 and CD8 T cells. In immunodeficient mice, in which human T cells induced xenogeneic GVHD, administration of 0.1 μg BsAb per dose depleted the majority of T cells from the peripheral blood, and 10 μg per dose completely reversed established GVHD and achieved a 100% survival rate. In mice bearing NALM6-luc xenografts, treatment with CD3×CD19 BsAb and activated human T cells induced complete remission of the leukemia, and all treated mice developed GVHD by 50 days after treatment. CD3×CD3 BsAb (3-30 μg doses) reversed clinical signs of GVHD, allowing long term follow-up beyond 250 days. T cells were undetectable by polymerase chain reaction in 4 of 5 mice in the 30 μg CD3×CD3 BsAb group 180 days after leukemia injection, and complete necropsies on day 259 revealed no evidence of human T cells or leukemia cells. Curing GVHD allows for long-term follow-up of tumor response heretofore impossible in humanized mouse models. Further studies are warranted to determine whether the CD3×CD3 BsAb has potential for treating clinical GVHD and other autoimmune diseases in humans.

Published
2025
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4. Clonal evolution during metastatic spread in high-risk neuroblastoma

Author

Gundem, Gunes, Levine, Max F., Roberts, Stephen S., Cheung, Irene Y., Medina-Martínez, Juan S., Feng, Yi, Arango-Ossa, Juan E., Chadoutaud, Loic, Rita, Mathieu, Asimomitis, Georgios, Zhou, Joe, You, Daoqi, Bouvier, Nancy, Spitzer, Barbara, Solit, David B., Dela Cruz, Filemon, LaQuaglia, Michael P., Kushner, Brian H., Modak, Shakeel, Shukla, Neerav, Iacobuzio-Donahue, Christine A., Kung, Andrew L., Cheung, Nai-Kong V., and Papaemmanuil, Elli

Published
2023
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5. Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells

Author

Qin Liu, Archana Thakur, Lawrence G Lum, Dana Schalk, Anthony F Shields, Daniel W Lee, Nai-Kong V Cheung, Maxim Yankelevich, Shakeel Modak, Roland Chu, Jeffrey Taub, Alissa Martin, Amy Schienshang, Sarah Whitaker, and Katie Rea

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

Background The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.Methods The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion.Results Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2–3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.Conclusions This study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.

Published
2024
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8. Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies

Author

Kim Kramer, Neeta Pandit-Taskar, Brian H. Kushner, Pat Zanzonico, John L. Humm, Ursula Tomlinson, Maria Donzelli, Suzanne L. Wolden, Sophia Haque, Ira Dunkel, Mark M. Souweidane, Jeffrey P. Greenfield, Satish Tickoo, Jason S. Lewis, Serge K. Lyashchenko, Jorge A. Carrasquillo, Bae Chu, Christopher Horan, Steven M. Larson, Nai-Kong V. Cheung, and Shakeel Modak

Subjects
CNS tumors, CNS metastases, Radioimmunotherapy, B7H3, Omburtamab, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies. Patients and methods We conducted a phase I trial of intraventricular 131I-omburtamab using a standard 3 + 3 design. Eligibility criteria included adequate cerebrospinal fluid (CSF) flow, no major organ toxicity, and for patients > dose level 6, availability of autologous stem cells. Patients initially received 74 MBq radioiodinated omburtamab to evaluate dosimetry and biodistribution followed by therapeutic 131I-omburtamab dose-escalated from 370 to 2960 MBq. Patients were monitored clinically and biochemically for toxicity graded using CTCAEv 3.0. Dosimetry was evaluated using serial CSF and blood sampling, and serial PET or gamma-camera scans. Patients could receive a second cycle in the absence of grade 3/4 non-hematologic toxicity or progressive disease. Results Thirty-eight patients received 100 radioiodinated omburtamab injections. Diagnoses included metastatic neuroblastoma (n = 16) and other B7H3-expressing solid tumors (n = 22). Thirty-five patients received at least 1 cycle of treatment with both dosimetry and therapy doses. Acute toxicities included

Published
2022
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9. Connecting telomere maintenance and regulation to the developmental origin and differentiation states of neuroblastoma tumor cells

Author

Eun Young Yu, Nai-Kong V. Cheung, and Neal F. Lue

Subjects
Neuroblastoma, Telomeres, Telomere maintenance mechanisms, Telomerase, ALT, Tumor cell differentiation, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract A cardinal feature that distinguishes clinically high-risk neuroblastoma from low-risk tumors is telomere maintenance. Specifically, neuroblastoma tumors with either active telomerase or alternative lengthening of telomeres exhibit aggressive growth characteristics that lead to poor outcomes, whereas tumors without telomere maintenance can be managed with observation or minimal treatment. Even though the need for cancer cells to maintain telomere DNA—in order to sustain cell proliferation—is well established, recent studies suggest that the neural crest origin of neuroblastoma may enforce unique relationships between telomeres and tumor malignancy. Specifically in neuroblastoma, telomere structure and telomerase activity are correlated with the adrenergic/mesenchymal differentiation states, and manipulating telomerase activity can trigger tumor cell differentiation. Both findings may reflect features of normal neural crest development. This review summarizes recent advances in the characterization of telomere structure and telomere maintenance mechanisms in neuroblastoma and discusses the findings in the context of relevant literature on telomeres during embryonic and neural development. Understanding the canonical and non-canonical roles of telomere maintenance in neuroblastoma could reveal vulnerabilities for telomere-directed therapies with potential applications to other pediatric malignancies.

Published
2022
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10. Identification of immunotherapy and radioimmunotherapy targets on desmoplastic small round cell tumors

Author

Madelyn Espinosa-Cotton, Hong-Fen Guo, Satish K. Tickoo, and Nai-Kong V. Cheung

Subjects
tumor-associated antigen (TAA), immunotherapy, radioimmunotherapy, bispecific antibodies (BsAbs), T cell engaging bispecific antibodies, desmoplastic small round cell tumor, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundDevelopment of successful antibody-based immunotherapeutic and radioimmunotherapeutic strategies rely on the identification of cell surface tumor-associated antigens (TAA) with restricted expression on normal tissues. Desmoplastic small round cell tumor (DSRCT) is a rare and generally neglected malignancy that primarily affects adolescent and young adult males. New therapies capable of treating disseminated disease are needed for DSRCT, which is often widespread at diagnosis.MethodsWe used immunohistochemistry (IHC) on fresh frozen surgical specimens and patient-derived xenograft (PDX) tumors and flow cytometry on DSRCT cell lines to evaluate expression of TAAs in these tumors. In vitro cytotoxicity assays were used to evaluate the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets. In vivo, we used an intraperitoneal xenograft mouse model of DSRCT to test T-BsAbs against several TAAs.ResultsIn DSRCT specimens we found widespread expression of B7-H3, EGFR, GD2, HER2, mesothelin, and polysialic acid, clinical targets for which specific antibody therapeutics are available. The expression of B7-H3, EGFR, HER2, and mesothelin was confirmed on the cell surface of DSRCT cell lines. In vitro cytotoxicity assays confirmed the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets against DSRCT cells. Remarkably, a HER2xCD3 T-BsAb was capable of completely shrinking established tumors in an intraperitoneal mouse model of DSRCT.ConclusionsWe propose that these TAAs should be further investigated in preclinical models as targets for immunotherapy and radioimmunotherapy with the hope of providing a rationale to extend these therapies to patients with advanced DSRCT.

Published
2023
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11. Targeting tumor vasculature to improve antitumor activity of T cells armed ex vivo with T cell engaging bispecific antibody

Author

Madelyn Espinosa-Cotton, Hong-fen Guo, Nai-Kong V Cheung, Jeong A Park, and Sébastien Monette

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

Background Success of T cell immunotherapy hinges on the tumor microenvironment (TME), and abnormal tumor vasculature is a hallmark of most solid tumors and associated with immune evasion. The efficacy of T cell engaging bispecific antibody (BsAb) treatment relies on the successful trafficking and cytolytic activity of T cells in solid tumors. Normalization of tumor vasculature using vascular endothelial growth factor (VEGF) blockades could improve efficacy of BsAb-based T cell immunotherapy.Methods Anti-human VEGF (bevacizumab, BVZ) or anti-mouse VEGFR2 antibody (DC101) was used as VEGF blockade, and ex vivo armed T cells (EATs) carrying anti-GD2, anti-HER2, or anti-glypican3 (GPC3) IgG-(L)-scFv platformed BsAb were used. BsAb-driven intratumoral T cell infiltration and in vivo antitumor response were evaluated using cancer cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) carried out in BALB-Rag2-/-IL-2R-γc-KO (BRG) mice. VEGF expression on human cancer cell lines was analyzed by flow cytometry, and VEGF levels in mouse serum were measured using VEGF Quantikine ELISA Kit. Tumor infiltrating lymphocytes (TILs) were evaluated using flow cytometry and by bioluminescence; both TILs and tumor vasculature were studied using immunohistochemistry.Results VEGF expression on cancer cell lines increased with seeding density in vitro. BVZ significantly reduced serum VEGF levels in mice. BVZ or DC101 increased high endothelial venules (HEVs) in the TME and substantially enhanced (2.1–8.1 fold) BsAb-driven T cell infiltration into neuroblastoma and osteosarcoma xenografts, which was preferential for CD8(+) TILs versus CD4(+) TILs, leading to superior antitumor effects in multiple CDX and PDX tumor models without added toxicities.Conclusions VEGF blockade using specific antibodies against VEGF or VEGFR2 increased HEVs in the TME and cytotoxic CD8(+) TILs, significantly improving the therapeutic efficacy of EAT strategies in preclinical models, supporting the clinical investigation of VEGF blockades to further enhance BsAb-based T cell immunotherapies.

Published
2023
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13. Skeletal muscle metastases in neuroblastoma share common progenitors with primary tumor and biologically resemble stage MS disease

Author

Christina Fong, Brian H. Kushner, Angela Di Giannatale, Gunes Gundem, Shanita Li, Stephen S. Roberts, Ellen M. Basu, Anita Price, Nai-Kong V. Cheung, and Shakeel Modak

Subjects
neuroblastoma, metastasis, skeletal muscle metastasis, pediatric oncology, chemotherapy, tumor evolution, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

IntroductionWhile subcutaneous metastases are often observed with stage MS neuroblastoma, an entity that usually resolves spontaneously, skeletal muscle metastases (SMM) have been rarely described. The purpose of this retrospective study was to investigate the significance of SMM in neuroblastoma.Patients and methodsSeventeen patients with neuroblastoma SMM were diagnosed at a median age of 4.3 (0.1-15.6) months. All had SMM at diagnosis and metastases at other sites. Fifteen (88%) had ≥ 2 SMM in disparate muscle groups. One, 14, and 2 patients had low, intermediate, and high-risk disease respectively. Fifteen tumors had favorable histology without MYCN amplification, and 2 were MYCN-amplified. Most SMM (80%; n=12/15 evaluated) were MIBG-avid.ResultsOnly 1 patient (with MYCN-non-amplified neuroblastoma) had disease progression. All survive at median follow-up of 47.9 (16.9-318.9) months post-diagnosis. Biological markers (histology, chromosomal and genetic aberrations) were not prognostic. Whole genome sequencing of 3 matched primary and SMM lesions suggested that both primary and metastatic tumors arose from the same progenitor. SMM completely resolved in 10 patients by 12 months post-diagnosis. Of 4 patients managed with watchful observation alone without any cytotoxic therapy, 3 maintain complete remission with SMM resolving by 5, 13, and 21 months post-diagnosis respectively.ConclusionsChildren with neuroblastoma SMM have an excellent prognosis, with a clinical course suggestive of stage MS disease. Based on these results, the initial management of infants with non-MYCN-amplified NB with SMM could be watchful observation, which could eliminate or reduce exposure to genotoxic therapy.

Published
2023
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14. Reciprocal impacts of telomerase activity and ADRN/MES differentiation state in neuroblastoma tumor biology

Author

Eun Young Yu, Syed S. Zahid, Sarah Aloe, Erik Falck-Pedersen, Xi Kathy Zhou, Nai-Kong V. Cheung, and Neal F. Lue

Subjects
Biology (General), QH301-705.5
Abstract

Yu et al. identify marked differences in the telomere and immunologic profiles of neuroblastoma cell lines displaying MES and ADRN lineage characteristics. They show that pharmacologically converting ADRN into MES cells triggers associated switch in telomere/immunologic protein profiles whereas inhibiting telomerase activity in ADRN cells induces reversible conversion into MES cells.

Published
2021
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15. Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response

Author

Jeong A. Park, Linlin Wang, and Nai-Kong V. Cheung

Subjects
Bispecific antibody, Dexamethasone, Disialogangliosides, Ex vivo bispecific antibody armed T-cells (EATs), Human epidermal growth factor receptor 2 (HER2), Immunotherapy, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesis, growth, proliferation, and metastasis, while derailing the host anti-tumor response. TME impedes bispecific antibody (BsAb) or chimeric antigen receptor (CAR)-driven T cells infiltration, survival, and cytotoxic efficacy. Modulating tumor infiltrating myeloid cells (TIMs) could potentially improve the efficacy of BsAb. Methods We evaluated the effects of TIM modulation on BsAb-driven T cell infiltration into tumors, their persistence, and in vivo anti-tumor response. Anti-GD2 BsAb and anti-HER2 BsAb built on IgG-[L]-scFv platform were tested against human cancer xenografts in BALB-Rag2 −/−IL-2R-γc-KO (BRG) mice. Depleting antibodies specific for polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic MDSC (M-MDSC), and tumor associated macrophage (TAM) were used to study the role of each TIM component. Dexamethasone, an established anti-inflammatory agent, was tested for its effect on TIMs. Results BsAb-driven T cells recruited myeloid cells into human tumor xenografts. Each TIM targeting therapy depleted cells of interest in blood and in tumors. Depletion of PMN-MDSCs, M-MDSCs, and particularly TAMs was associated with enhanced T cell infiltration into tumors, significantly improving tumor control and survival in multiple cancer xenograft models. Dexamethasone premedication depleted monocytes in circulation and TAMs in tumors, enhanced BsAb-driven T cell infiltration, and anti-tumor response with survival benefit. Conclusion Reducing TIMs markedly enhanced anti-tumor effects of BsAb-based T cell immunotherapy by improving intratumoral T cell infiltration and persistence. TAM depletion was more effective than PMN- or M-MDSCs depletion at boosting the anti-tumor response of T cell engaging BsAb.

Published
2021
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18. Desmoplastic small round cell tumor cancer stem cell-like cells resist chemotherapy but remain dependent on the EWSR1-WT1 oncoprotein

Author

Justin W. Magrath, Hong-Jun Kang, Alifiani Hartono, Madelyn Espinosa-Cotton, Romel Somwar, Marc Ladanyi, Nai-Kong V. Cheung, and Sean B. Lee

Subjects
DSRCT, pediatric cancer, cancer stem cells, chemoresistance, sarcoma, Biology (General), QH301-705.5
Abstract

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive pediatric cancer driven by the EWSR1-WT1 fusion oncogene. Combinations of chemotherapy, radiation and surgery are not curative, and the 5-years survival rate is less than 25%. One potential explanation for refractoriness is the existence of a cancer stem cell (CSC) subpopulation able escape current treatment modalities. However, no study to-date has examined the role of CSCs in DSRCT or established in vitro culture conditions to model this subpopulation. In this study, we investigated the role of stemness markers in DSRCT survival and metastasis, finding that elevated levels of SOX2 and NANOG are associated with worse survival in sarcoma patients and are elevated in metastatic DSRCT tumors. We further develop the first in vitro DSRCT CSC model which forms tumorspheres, expresses increased levels of stemness markers (SOX2, NANOG, KLF4, and OCT4), and resists doxorubicin chemotherapy treatment. This model is an important addition to the DSRCT tool kit and will enable investigation of this critical DSRCT subpopulation. Despite lower sensitivity to chemotherapy, the DSRCT CSC model remained sensitive to knockdown of the EWSR1-WT1 fusion protein, suggesting that future therapies directed against this oncogenic driver have the potential to treat both DSRCT bulk tumor and CSCs.

Published
2022
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20. Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten.

Author

Vaughn, Brett A., Lee, Sang-gyu, Vargas, Daniela Burnes, Seo, Shin, Rinne, Sara S., Xu, Hong, Guo, Hong-fen, Le Roux, Alexandre B., Gajecki, Leah, Krebs, Simone, Yang, Guangbin, Ouerfelli, Ouathek, Zanzonico, Pat B., Fung, Edward K., St. Jean, Samantha, Carrasco, Sebastian E., Jungbluth, Achim, Cheung, Nai Kong V., Larson, Steven M., and Veach, Darren R.

Published
2024
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21. Ovarian function in female survivors of high‐risk neuroblastoma.

Author

Jimenez‐Kurlander, Lauren, DeRosa, Amelia, Kostrzewa, Caroline E., Moskowitz, Chaya S., Bogardus, Kimberly, Antal, Zoltan, Wolden, Suzanne, La Quaglia, Michael P., Basu, Ellen M., Cardenas, Fiorella Iglesias, Kramer, Kim, Kushner, Brian H., Cheung, Nai‐Kong V., Modak, Shakeel, and Friedman, Danielle Novetsky

Published
2024
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25. GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma

Author

Jeong A. Park and Nai-Kong V. Cheung

Subjects
Osteosarcoma, Immunotherapy, Bispecific antibody, Disialogangliosides, Human epidermal growth factor receptor-2, T cell arming, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs). Methods We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h 51Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2 −/−IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells (EATs) and studied their tumor-suppressive effect against osteosarcoma xenografts. In order to improve the anti-tumor response, ICIs, anti-human PD-1 (pembrolizumab) or anti-human PD-L1 (atezolizumab) antibodies were tested their synergy with GD2- or HER2-BsAb against osteosarcoma. Results GD2 and HER2 were chosen from a panel of surface markers on osteosarcoma cell lines and PDXs. Anti-GD2 BsAb or anti-HER2 BsAb exerted potent anti-tumor effect against osteosarcoma tumors in vitro and in vivo. T cells armed with anti-GD2-BsAb (GD2-EATs) or anti-HER2-BsAb (HER2-EATs) showed significant anti-tumor activities as well. Anti-PD-L1 combination treatment enhanced BsAb-armed T cell function in vivo and improved tumor control and survival of the mice, when given sequentially and continuously. Conclusion Anti-GD2 and anti-HER2 BsAbs were effective in controlling osteosarcoma. These data support the clinical investigation of GD2 and HER2 targeted T-BsAb treatment in combination with immune checkpoint inhibitors, particularly anti-PD-L1, in patients with osteosarcoma to improve their treatment outcome.

Published
2020
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26. Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations

Author

Samuel W. Brady, Yanling Liu, Xiaotu Ma, Alexander M. Gout, Kohei Hagiwara, Xin Zhou, Jian Wang, Michael Macias, Xiaolong Chen, John Easton, Heather L. Mulder, Michael Rusch, Lu Wang, Joy Nakitandwe, Shaohua Lei, Eric M. Davis, Arlene Naranjo, Cheng Cheng, John M. Maris, James R. Downing, Nai-Kong V. Cheung, Michael D. Hogarty, Michael A. Dyer, and Jinghui Zhang

Subjects
Science
Abstract

Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.

Published
2020
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32. Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor

Author

Madelyn Espinosa-Cotton and Nai-Kong V. Cheung

Subjects
DSRCT = desmoplastic small round cell tumor, antibodies, immunotherapy, targeted therapy, radioimmunotherapy, CAR T cell, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primarily affects adolescent and young adult males. The 5-year survival rate is 15-30% and few curative treatment options exist. Although there is no standard treatment for DSRCT, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of PDGFA and IGF-1R, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. As in cancer in general, interest in immunotherapy to treat DSRCT has increased in recent years. To that end, several types of immunotherapy are now being tested clinically, including monoclonal antibodies, radionuclide-conjugated antibodies, chimeric antigen receptor T cells, checkpoint inhibitors, and bispecific antibodies (BsAbs). These types of therapies may be particularly useful in DSRCT, which is frequently characterized by widespread intraperitoneal implants, which are difficult to completely remove surgically and are the frequent cause of relapse. Successful treatment with immunotherapy or radioimmunotherapy following debulking surgery could eradiate these micrometasteses and prevent relapse. Although there has been limited success to date for immunotherapy in pediatric solid tumors, the significant improvements in survival seen in the treatment of other pediatric solid tumors, such as metastatic neuroblastoma and its CNS spread, suggest a potential of immunotherapy and specifically compartmental immunotherapy in DSRCT.

Published
2021
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34. Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Author

Cobianchi, L, Piccolo, D, Dal Mas, F, Agnoletti, V, Ansaloni, L, Balch, J, Biffl, W, Butturini, G, Catena, F, Coccolini, F, Denicolai, S, De Simone, B, Frigerio, I, Fugazzola, P, Marseglia, G, Martellucci, J, Modenese, M, Previtali, P, Ruta, F, Venturi, A, Kaafarani, H, Loftus, T, Abbott, K, Abdelmalik, A, Abebe, N, Abu-Zidan, F, Adam, Y, Adamou, H, Adamovich, D, Agresta, F, Agrusa, A, Akin, E, Alessiani, M, Alexandrino, H, Ali, S, Mihai, V, Almeida, P, Al-Shehari, M, Altomare, M, Amico, F, Ammendola, M, Andreuccetti, J, Anestiadou, E, Angelos, P, Annicchiarico, A, Antonelli, A, Aparicio-Sanchez, D, Ardito, A, Argenio, G, Arvieux, C, Askevold, I, Atanasov, B, Augustin, G, Awad, S, Bacchiocchi, G, Bagnoli, C, Bahouth, H, Baili, E, Bains, L, Baiocchi, G, Bala, M, Balague, C, Balalis, D, Baldini, E, Baraket, O, Baral, S, Barone, M, Barranquero, A, Barreras, J, Bass, G, Bayhan, Z, Bellanova, G, Ben-Ishay, O, Bert, F, Bianchi, V, Biancuzzi, H, Bidoli, C, Radulescu, R, Bignell, M, Biloslavo, A, Bini, R, Bissacco, D, Boati, P, Boddaert, G, Bogdanic, B, Bombardini, C, Bonavina, L, Bonomo, L, Bottari, A, Bouliaris, K, Brachini, G, Brillantino, A, Brisinda, G, Bulanauca, M, Buonomo, L, Burcharth, J, Buscemi, S, Calabretto, F, Calini, G, Calu, V, Campanile, F, Dall'Orto, R, Campos-Serra, A, Campostrini, S, Capoglu, R, Carvas, J, Cascella, M, Pattacini, G, Celentano, V, Centonze, D, Ceresoli, M, Chatzipetris, D, Chessa, A, Chiarello, M, Chirica, M, Chooklin, S, Chouliaras, C, Chowdhury, S, Cianci, P, Cillara, N, Cimbanassi, S, Cioffi, S, Colak, E, Ruiz, E, Conti, L, Coppola, A, De Sa, T, Costa, S, Cozza, V, Curro', G, Dabekaussen, K, D'Acapito, F, Damaskos, D, D'Ambrosio, G, Das, K, Davies, R, De Beaux, A, Fernandez, S, De Luca, A, De Stefano, F, Degrate, L, Demetrashvili, Z, Demetriades, A, Detanac, D, Dezi, A, Di Buono, G, Di Carlo, I, Di Lascio, P, Di Martino, M, Di Saverio, S, Diaconescu, B, Diaz, J, Dibra, R, Dimitrov, E, Dinuzzi, V, Dios-Barbeito, S, Diyani, J, Dogjani, A, Domanin, M, D'Oria, M, Munoz-Cruzado, V, East, B, Ekelund, M, Ekwen, G, Elbaih, A, Elhadi, M, Enninghorst, N, Ernisova, M, Escalera-Antezana, J, Esposito, S, Esposito, G, Estaire, M, Fare, C, Farre, R, Favi, F, Ferrario, L, Vajana, A, Filisetti, C, Fleres, F, Fonseca, V, Forero-Torres, A, Forfori, F, Fortuna, L, Fradelos, E, Fraga, G, Fransvea, P, Frassini, S, Frazzetta, G, Pizzocaro, E, Frountzas, M, Gachabayov, M, Galeiras, R, Vazquez, A, Gargarella, S, Garzali, I, Ghannam, W, Ghazi, F, Gillman, L, Gioco, R, Giordano, A, Giordano, L, Giove, C, Giraudo, G, Giuffrida, M, Capponi, M, Gois, E, Gomes, C, Gomes, F, Gonsaga, R, Gonullu, E, Goosen, J, Goranovic, T, Gracia-Roman, R, Graziano, G, Griffiths, E, Guagni, T, Hadzhiev, D, Haidar, M, Hamid, H, Hardcastle, T, Hayati, F, Healey, A, Hecker, A, Hecker, M, Garcia, E, Hodonou, A, Huaman, E, Huerta, M, Ibrahim, A, Ibrahim, B, Ietto, G, Inama, M, Ioannidis, O, Isik, A, Ismail, N, Ismail, A, Jailani, R, Jang, J, Kalfountzos, C, Kalipershad, S, Kaouras, E, Kaplan, L, Kara, Y, Karamagioli, E, Karamarkovia, A, Katsaros, I, Kavalakat, A, Kechagias, A, Kenig, J, Kessel, B, Khan, J, Khokha, V, Kim, J, Kirkpatrick, A, Klappenbach, R, Kluger, Y, Kobe, Y, Lymperis, E, Kok, K, Kong, V, Korkolis, D, Koukoulis, G, Kovacevic, B, Kruger, V, Kryvoruchko, I, Kurihara, H, Kuriyama, A, Landaluce-Olavarria, A, Lapolla, P, Leppaniemi, A, Licari, L, Lisi, G, Litvin, A, Lizarazu, A, Bayo, H, Lohsiriwat, V, Moreira, C, Lostoridis, E, Luna, A, Luppi, D, Machain, V, Maegele, M, Maggiore, D, Magnone, S, Maier, R, Major, P, Manangi, M, Manetti, A, Mantoglu, B, Marafante, C, Mariani, F, Marinis, A, Mariot, E, Martines, G, Perez, A, Martino, C, Mascagni, P, Massalou, D, Massaro, M, Matias-Garcia, B, Mazzarella, G, Mazzarolo, G, Melo, R, Mendoza-Moreno, F, Meric, S, Meyer, J, Miceli, L, Michalopoulos, N, Milana, F, Mingoli, A, Mishra, T, Mohamed, M, Mohamedahmed, A, Mohammed, M, Mohan, R, Moore, E, Morales-Garcia, D, Muhrbeck, M, Mulita, F, Mustafa, S, Muttillo, E, Naimzada, M, Navsaria, P, Negoi, I, Nespoli, L, Nguyen, C, Nidaw, M, Nigri, G, Nikolopoulos, I, O'Connor, D, Ogundipe, H, Oliveri, C, Olmi, S, Ong, E, Orecchia, L, Osipov, A, Othman, M, Pace, M, Pacilli, M, Pagani, L, Palomba, G, Pantalone, D, Panyko, A, Paolillo, C, Papa, M, Papaconstantinou, D, Papadoliopoulou, M, Papadopoulos, A, Papis, D, Pararas, N, Parreira, J, Parry, N, Pata, F, Patel, T, Paterson-Brown, S, Pavone, G, Pecchini, F, Pegoraro, V, Pellino, G, Pelloni, M, Peloso, A, Del Pozo, E, Pereira, R, Pereira, B, Perez, S, Perra, T, Perrone, G, Pesce, A, Petagna, L, Petracca, G, Phupong, V, Picardi, B, Picciariello, A, Piccoli, M, Picetti, E, Pikoulis, E, Pintar, T, Pirozzolo, G, Piscioneri, F, Podda, M, Porcu, A, Privitera, F, Punzo, C, Quaresima, S, Quiodettis, M, Qvist, N, Rahim, R, de Almeida, F, Ramely, R, Rasa, H, Reichert, M, Reinisch-Liese, A, Renne, A, Riccetti, C, Rodriguez-Luna, M, Roizblatt, D, Romanzi, A, Romeo, L, Roscio, F, Rosnelifaizur, R, Rossi, S, Rubiano, A, Ruiz-Ucar, E, Sakakushev, B, Salamea, J, Sall, I, Samarakoon, L, Sammartano, F, Arteaga, A, Sanchez-Cordero, S, Santoanastaso, D, Sartelli, M, Sasia, D, Sato, N, Savchuk, A, Sawyer, R, Scaioli, G, Schizas, D, Sebastiani, S, Seeliger, B, Lohse, H, Seretis, C, Sermonesi, G, Serradilla-Martin, M, Shelat, V, Shlyapnikov, S, Sidiropoulos, T, Simoes, R, Siragusa, L, Siribumrungwong, B, Slavchev, M, Solaini, L, Soldini, G, Sopuev, A, Soreide, K, Sovatzidis, A, Stahel, P, Strickland, M, Sultan, M, Sydorchuk, R, Sydorchuk, L, Syed, S, Tallon-Aguilar, L, Tamburini, A, Tamini, N, Tan, E, Tan, J, Tarasconi, A, Tartaglia, N, Tartaglia, G, Tartaglia, D, Taylor, J, Tebala, G, Teuben, M, Theodorou, A, Tolonen, M, Tomasicchio, G, Toro, A, Torre, B, Triantafyllou, T, Trigiante, G, Tripepi, M, Trostchansky, J, Tsekouras, K, Turrado-Rodriguez, V, Tutino, R, Uccelli, M, Uchikov, P, Ugarte-Sierra, B, Ukkonen, M, Vailas, M, Vassiliu, P, Vazquez, R, Velmahos, G, Verde, J, Veroux, M, Vigano, J, Vilallonga, R, Visconti, D, Vittori, A, Waledziak, M, Wannatoop, T, Widmer, L, Wilson, M, Woltz, S, Wong, T, Xenaki, S, Yu, B, Yule, S, Zachariah, S, Zacharis, G, Zaghi, C, Zakaria, A, Zambrano, D, Zampitis, N, Zampogna, B, Zanghi, S, Zantedeschi, M, Zapsalis, K, Zattoni, F, Zese, M, Cobianchi L., Piccolo D., Dal Mas F., Agnoletti V., Ansaloni L., Balch J., Biffl W., Butturini G., Catena F., Coccolini F., Denicolai S., De Simone B., Frigerio I., Fugazzola P., Marseglia G., Marseglia G. R., Martellucci J., Modenese M., Previtali P., Ruta F., Venturi A., Kaafarani H. M., Loftus T. J., Abbott K. L., Abdelmalik A., Abebe N. S., Abu-Zidan F., Adam Y. A. Y., Adamou H., Adamovich D. M., Agresta F., Agrusa A., Akin E., Alessiani M., Alexandrino H., Ali S. M., Mihai V. A., Almeida P. M., Al-Shehari M. M., Altomare M., Amico F., Ammendola M., Andreuccetti J., Anestiadou E., Angelos P., Annicchiarico A., Antonelli A., Aparicio-Sanchez D., Ardito A., Argenio G., Arvieux C. C., Askevold I. H., Atanasov B. T., Augustin G., Awad S. S., Bacchiocchi G., Bagnoli C., Bahouth H., Baili E., Bains L., Baiocchi G. L., Bala M., Balague C., Balalis D., Baldini E., Baraket O., Baral S., Barone M., Barranquero A. G., Barreras J. A., Bass G. A., Bayhan Z., Bellanova G., Ben-Ishay O., Bert F., Bianchi V., Biancuzzi H., Bidoli C., Radulescu R. B., Bignell M. B., Biloslavo A., Bini R., Bissacco D., Boati P., Boddaert G., Bogdanic B., Bombardini C., Bonavina L., Bonomo L., Bottari A., Bouliaris K., Brachini G., Brillantino A., Brisinda G., Bulanauca M. M., Buonomo L. A., Burcharth J., Buscemi S., Calabretto F., Calini G., Calu V., Campanile F. C., Dall'Orto R. C., Campos-Serra A., Campostrini S., Capoglu R., Carvas J. M., Cascella M., Pattacini G. C., Celentano V., Centonze D. C., Ceresoli M., Chatzipetris D., Chessa A., Chiarello M. M., Chirica M., Chooklin S., Chouliaras C., Chowdhury S., Cianci P., Cillara N., Cimbanassi S., Cioffi S. P. B., Colak E., Ruiz E. C., Conti L., Coppola A., De Sa T. C., Costa S. D., Cozza V., Curro' G., Dabekaussen K. F. A. -S. A., D'acapito F., Damaskos D., D'ambrosio G., Das K., Davies R. J., De Beaux A. C., Fernandez S. P. L., De Luca A., De Stefano F., Degrate L., Demetrashvili Z., Demetriades A. K., Detanac D. S., Dezi A., Di Buono G., Di Carlo I., Di Lascio P., Di Martino M., Di Saverio S., Diaconescu B., Diaz J. J., Dibra R., Dimitrov E. N., Dinuzzi V. P., Dios-Barbeito S., Diyani J. F. A., Dogjani A., Domanin M., D'Oria M., Munoz-Cruzado V. D., East B., Ekelund M., Ekwen G. T., Elbaih A. H., Elhadi M., Enninghorst N., Ernisova M., Escalera-Antezana J. P., Esposito S., Esposito G., Estaire M., Fare C. N., Farre R., Favi F., Ferrario L., Vajana A. F. T., Filisetti C., Fleres F., Fonseca V. C., Forero-Torres A., Forfori F., Fortuna L., Fradelos E., Fraga G. P., Fransvea P., Frassini S., Frazzetta G., Pizzocaro E., Frountzas M., Gachabayov M., Galeiras R., Vazquez A. A. G., Gargarella S., Garzali I. U., Ghannam W. M., Ghazi F. N., Gillman L. M., Gioco R., Giordano A., Giordano L., Giove C., Giraudo G., Giuffrida M., Capponi M. G., Gois E., Gomes C. A., Gomes F. C., Gonsaga R. A. T., Gonullu E., Goosen J., Goranovic T., Gracia-Roman R., Graziano G. M. P., Griffiths E. A., Guagni T., Hadzhiev D. B., Haidar M. G., Hamid H. K. S., Hardcastle T. C., Hayati F., Healey A. J., Hecker A., Hecker M., Garcia E. F. H., Hodonou A. M., Huaman E. C., Huerta M., Ibrahim A. F., Ibrahim B. M. S., Ietto G., Inama M., Ioannidis O., Isik A., Ismail N., Ismail A. M. H., Jailani R. F., Jang J. Y., Kalfountzos C., Kalipershad S. N. R., Kaouras E., Kaplan L. J., Kara Y., Karamagioli E., Karamarkovia A., Katsaros I., Kavalakat A. J., Kechagias A., Kenig J., Kessel B. J., Khan J. S., Khokha V., Kim J. I., Kirkpatrick A. W., Klappenbach R., Kluger Y., Kobe Y., Lymperis E. K., Kok K. Y. Y., Kong V., Korkolis D. P., Koukoulis G., Kovacevic B., Kruger V. F., Kryvoruchko I. A., Kurihara H., Kuriyama A., Landaluce-Olavarria A., Lapolla P., Leppaniemi A., Licari L., Lisi G., Litvin A., Lizarazu A., Bayo H. L., Lohsiriwat V., Moreira C. C. L., Lostoridis E., Luna A. T., Luppi D., Machain V. G. M., Maegele M., Maggiore D., Magnone S., Maier R. V., Major P., Manangi M., Manetti A., Mantoglu B., Marafante C., Mariani F., Marinis A., Mariot E. A. S., Martines G., Perez A. M., Martino C., Mascagni P., Massalou D., Massaro M., Matias-Garcia B., Mazzarella G., Mazzarolo G., Melo R. B., Mendoza-Moreno F., Meric S., Meyer J., Miceli L., Michalopoulos N. V., Milana F., Mingoli A., Mishra T. S., Mohamed M., Mohamed M. I. E. A., Mohamedahmed A. Y., Mohammed M. J. S., Mohan R., Moore E. E., Morales-Garcia D., Muhrbeck M., Mulita F., Mustafa S. M. S., Muttillo E. M., Naimzada M. D., Navsaria P. H., Negoi I., Nespoli L., Nguyen C., Nidaw M. K., Nigri G., Nikolopoulos I., O'connor D. B., Ogundipe H. D., Oliveri C., Olmi S., Ong E. C. W., Orecchia L., Osipov A. V., Othman M. F., Pace M., Pacilli M., Pagani L., Palomba G., Pantalone D., Panyko A., Paolillo C., Papa M. V., Papaconstantinou D., Papadoliopoulou M., Papadopoulos A., Papis D., Pararas N., Parreira J. G., Parry N. G., Pata F., Patel T., Paterson-Brown S., Pavone G., Pecchini F., Pegoraro V., Pellino G., Pelloni M., Peloso A., Del Pozo E. P., Pereira R. G., Pereira B. M., Perez A. L., Perez S., Perra T., Perrone G., Pesce A., Petagna L., Petracca G., Phupong V., Picardi B., Picciariello A., Piccoli M., Picetti E., Pikoulis E. P., Pintar T., Pirozzolo G., Piscioneri F., Podda M., Porcu A., Privitera F., Punzo C., Quaresima S., Quiodettis M. A., Qvist N., Rahim R., de Almeida F. R., Ramely R. B., Rasa H. K., Reichert M., Reinisch-Liese A., Renne A., Riccetti C., Rodriguez-Luna M. R., Roizblatt D., Romanzi A., Romeo L., Roscio F. P. M., Rosnelifaizur R. B., Rossi S., Rubiano A. M., Ruiz-Ucar E., Sakakushev B. E., Salamea J. C., Sall I., Samarakoon L. B., Sammartano F., Arteaga A. S., Sanchez-Cordero S., Santoanastaso D. P. M., Sartelli M., Sasia D., Sato N., Savchuk A., Sawyer R. G., Scaioli G., Schizas D., Sebastiani S., Seeliger B., Lohse H. A. S., Seretis C., Sermonesi G., Serradilla-Martin M., Shelat V. G., Shlyapnikov S., Sidiropoulos T., Simoes R. L., Siragusa L., Siribumrungwong B., Slavchev M., Solaini L., Soldini G., Sopuev A., Soreide K., Sovatzidis A., Stahel P. F., Strickland M., Sultan M. A. H., Sydorchuk R., Sydorchuk L., Syed S. M. A. M., Tallon-Aguilar L., Tamburini A. M., Tamini N., Tan E. C. T. H., Tan J. H., Tarasconi A., Tartaglia N., Tartaglia G., Tartaglia D., Taylor J. V., Tebala G. D., Teuben M., Theodorou A., Tolonen M., Tomasicchio G., Toro A., Torre B., Triantafyllou T., Trigiante G. T., Tripepi M., Trostchansky J., Tsekouras K., Turrado-Rodriguez V., Tutino R., Uccelli M., Uchikov P. A., Ugarte-Sierra B., Ukkonen M. T., Vailas M., Vassiliu P. G., Vazquez A. G., Vazquez R. G., Velmahos G., Verde J. E., Verde J. M., Veroux M., Vigano J., Vilallonga R., Visconti D., Vittori A., Waledziak M., Wannatoop T., Widmer L. W., Wilson M. S. J., Woltz S., Wong T. H., Xenaki S., Yu B., Yule S., Zachariah S. K., Zacharis G., Zaghi C., Zakaria A. D., Zambrano D. A., Zampitis N., Zampogna B., Zanghi S., Zantedeschi M., Zapsalis K., Zattoni F., Zese M., Cobianchi, L, Piccolo, D, Dal Mas, F, Agnoletti, V, Ansaloni, L, Balch, J, Biffl, W, Butturini, G, Catena, F, Coccolini, F, Denicolai, S, De Simone, B, Frigerio, I, Fugazzola, P, Marseglia, G, Martellucci, J, Modenese, M, Previtali, P, Ruta, F, Venturi, A, Kaafarani, H, Loftus, T, Abbott, K, Abdelmalik, A, Abebe, N, Abu-Zidan, F, Adam, Y, Adamou, H, Adamovich, D, Agresta, F, Agrusa, A, Akin, E, Alessiani, M, Alexandrino, H, Ali, S, Mihai, V, Almeida, P, Al-Shehari, M, Altomare, M, Amico, F, Ammendola, M, Andreuccetti, J, Anestiadou, E, Angelos, P, Annicchiarico, A, Antonelli, A, Aparicio-Sanchez, D, Ardito, A, Argenio, G, Arvieux, C, Askevold, I, Atanasov, B, Augustin, G, Awad, S, Bacchiocchi, G, Bagnoli, C, Bahouth, H, Baili, E, Bains, L, Baiocchi, G, Bala, M, Balague, C, Balalis, D, Baldini, E, Baraket, O, Baral, S, Barone, M, Barranquero, A, Barreras, J, Bass, G, Bayhan, Z, Bellanova, G, Ben-Ishay, O, Bert, F, Bianchi, V, Biancuzzi, H, Bidoli, C, Radulescu, R, Bignell, M, Biloslavo, A, Bini, R, Bissacco, D, Boati, P, Boddaert, G, Bogdanic, B, Bombardini, C, Bonavina, L, Bonomo, L, Bottari, A, Bouliaris, K, Brachini, G, Brillantino, A, Brisinda, G, Bulanauca, M, Buonomo, L, Burcharth, J, Buscemi, S, Calabretto, F, Calini, G, Calu, V, Campanile, F, Dall'Orto, R, Campos-Serra, A, Campostrini, S, Capoglu, R, Carvas, J, Cascella, M, Pattacini, G, Celentano, V, Centonze, D, Ceresoli, M, Chatzipetris, D, Chessa, A, Chiarello, M, Chirica, M, Chooklin, S, Chouliaras, C, Chowdhury, S, Cianci, P, Cillara, N, Cimbanassi, S, Cioffi, S, Colak, E, Ruiz, E, Conti, L, Coppola, A, De Sa, T, Costa, S, Cozza, V, Curro', G, Dabekaussen, K, D'Acapito, F, Damaskos, D, D'Ambrosio, G, Das, K, Davies, R, De Beaux, A, Fernandez, S, De Luca, A, De Stefano, F, Degrate, L, Demetrashvili, Z, Demetriades, A, Detanac, D, Dezi, A, Di Buono, G, Di Carlo, I, Di Lascio, P, Di Martino, M, Di Saverio, S, Diaconescu, B, Diaz, J, Dibra, R, Dimitrov, E, Dinuzzi, V, Dios-Barbeito, S, Diyani, J, Dogjani, A, Domanin, M, D'Oria, M, Munoz-Cruzado, V, East, B, Ekelund, M, Ekwen, G, Elbaih, A, Elhadi, M, Enninghorst, N, Ernisova, M, Escalera-Antezana, J, Esposito, S, Esposito, G, Estaire, M, Fare, C, Farre, R, Favi, F, Ferrario, L, Vajana, A, Filisetti, C, Fleres, F, Fonseca, V, Forero-Torres, A, Forfori, F, Fortuna, L, Fradelos, E, Fraga, G, Fransvea, P, Frassini, S, Frazzetta, G, Pizzocaro, E, Frountzas, M, Gachabayov, M, Galeiras, R, Vazquez, A, Gargarella, S, Garzali, I, Ghannam, W, Ghazi, F, Gillman, L, Gioco, R, Giordano, A, Giordano, L, Giove, C, Giraudo, G, Giuffrida, M, Capponi, M, Gois, E, Gomes, C, Gomes, F, Gonsaga, R, Gonullu, E, Goosen, J, Goranovic, T, Gracia-Roman, R, Graziano, G, Griffiths, E, Guagni, T, Hadzhiev, D, Haidar, M, Hamid, H, Hardcastle, T, Hayati, F, Healey, A, Hecker, A, Hecker, M, Garcia, E, Hodonou, A, Huaman, E, Huerta, M, Ibrahim, A, Ibrahim, B, Ietto, G, Inama, M, Ioannidis, O, Isik, A, Ismail, N, Ismail, A, Jailani, R, Jang, J, Kalfountzos, C, Kalipershad, S, Kaouras, E, Kaplan, L, Kara, Y, Karamagioli, E, Karamarkovia, A, Katsaros, I, Kavalakat, A, Kechagias, A, Kenig, J, Kessel, B, Khan, J, Khokha, V, Kim, J, Kirkpatrick, A, Klappenbach, R, Kluger, Y, Kobe, Y, Lymperis, E, Kok, K, Kong, V, Korkolis, D, Koukoulis, G, Kovacevic, B, Kruger, V, Kryvoruchko, I, Kurihara, H, Kuriyama, A, Landaluce-Olavarria, A, Lapolla, P, Leppaniemi, A, Licari, L, Lisi, G, Litvin, A, Lizarazu, A, Bayo, H, Lohsiriwat, V, Moreira, C, Lostoridis, E, Luna, A, Luppi, D, Machain, V, Maegele, M, Maggiore, D, Magnone, S, Maier, R, Major, P, Manangi, M, Manetti, A, Mantoglu, B, Marafante, C, Mariani, F, Marinis, A, Mariot, E, Martines, G, Perez, A, Martino, C, Mascagni, P, Massalou, D, Massaro, M, Matias-Garcia, B, Mazzarella, G, Mazzarolo, G, Melo, R, Mendoza-Moreno, F, Meric, S, Meyer, J, Miceli, L, Michalopoulos, N, Milana, F, Mingoli, A, Mishra, T, Mohamed, M, Mohamedahmed, A, Mohammed, M, Mohan, R, Moore, E, Morales-Garcia, D, Muhrbeck, M, Mulita, F, Mustafa, S, Muttillo, E, Naimzada, M, Navsaria, P, Negoi, I, Nespoli, L, Nguyen, C, Nidaw, M, Nigri, G, Nikolopoulos, I, O'Connor, D, Ogundipe, H, Oliveri, C, Olmi, S, Ong, E, Orecchia, L, Osipov, A, Othman, M, Pace, M, Pacilli, M, Pagani, L, Palomba, G, Pantalone, D, Panyko, A, Paolillo, C, Papa, M, Papaconstantinou, D, Papadoliopoulou, M, Papadopoulos, A, Papis, D, Pararas, N, Parreira, J, Parry, N, Pata, F, Patel, T, Paterson-Brown, S, Pavone, G, Pecchini, F, Pegoraro, V, Pellino, G, Pelloni, M, Peloso, A, Del Pozo, E, Pereira, R, Pereira, B, Perez, S, Perra, T, Perrone, G, Pesce, A, Petagna, L, Petracca, G, Phupong, V, Picardi, B, Picciariello, A, Piccoli, M, Picetti, E, Pikoulis, E, Pintar, T, Pirozzolo, G, Piscioneri, F, Podda, M, Porcu, A, Privitera, F, Punzo, C, Quaresima, S, Quiodettis, M, Qvist, N, Rahim, R, de Almeida, F, Ramely, R, Rasa, H, Reichert, M, Reinisch-Liese, A, Renne, A, Riccetti, C, Rodriguez-Luna, M, Roizblatt, D, Romanzi, A, Romeo, L, Roscio, F, Rosnelifaizur, R, Rossi, S, Rubiano, A, Ruiz-Ucar, E, Sakakushev, B, Salamea, J, Sall, I, Samarakoon, L, Sammartano, F, Arteaga, A, Sanchez-Cordero, S, Santoanastaso, D, Sartelli, M, Sasia, D, Sato, N, Savchuk, A, Sawyer, R, Scaioli, G, Schizas, D, Sebastiani, S, Seeliger, B, Lohse, H, Seretis, C, Sermonesi, G, Serradilla-Martin, M, Shelat, V, Shlyapnikov, S, Sidiropoulos, T, Simoes, R, Siragusa, L, Siribumrungwong, B, Slavchev, M, Solaini, L, Soldini, G, Sopuev, A, Soreide, K, Sovatzidis, A, Stahel, P, Strickland, M, Sultan, M, Sydorchuk, R, Sydorchuk, L, Syed, S, Tallon-Aguilar, L, Tamburini, A, Tamini, N, Tan, E, Tan, J, Tarasconi, A, Tartaglia, N, Tartaglia, G, Tartaglia, D, Taylor, J, Tebala, G, Teuben, M, Theodorou, A, Tolonen, M, Tomasicchio, G, Toro, A, Torre, B, Triantafyllou, T, Trigiante, G, Tripepi, M, Trostchansky, J, Tsekouras, K, Turrado-Rodriguez, V, Tutino, R, Uccelli, M, Uchikov, P, Ugarte-Sierra, B, Ukkonen, M, Vailas, M, Vassiliu, P, Vazquez, R, Velmahos, G, Verde, J, Veroux, M, Vigano, J, Vilallonga, R, Visconti, D, Vittori, A, Waledziak, M, Wannatoop, T, Widmer, L, Wilson, M, Woltz, S, Wong, T, Xenaki, S, Yu, B, Yule, S, Zachariah, S, Zacharis, G, Zaghi, C, Zakaria, A, Zambrano, D, Zampitis, N, Zampogna, B, Zanghi, S, Zantedeschi, M, Zapsalis, K, Zattoni, F, Zese, M, Cobianchi L., Piccolo D., Dal Mas F., Agnoletti V., Ansaloni L., Balch J., Biffl W., Butturini G., Catena F., Coccolini F., Denicolai S., De Simone B., Frigerio I., Fugazzola P., Marseglia G., Marseglia G. R., Martellucci J., Modenese M., Previtali P., Ruta F., Venturi A., Kaafarani H. M., Loftus T. J., Abbott K. L., Abdelmalik A., Abebe N. S., Abu-Zidan F., Adam Y. A. Y., Adamou H., Adamovich D. M., Agresta F., Agrusa A., Akin E., Alessiani M., Alexandrino H., Ali S. M., Mihai V. A., Almeida P. M., Al-Shehari M. M., Altomare M., Amico F., Ammendola M., Andreuccetti J., Anestiadou E., Angelos P., Annicchiarico A., Antonelli A., Aparicio-Sanchez D., Ardito A., Argenio G., Arvieux C. C., Askevold I. H., Atanasov B. T., Augustin G., Awad S. S., Bacchiocchi G., Bagnoli C., Bahouth H., Baili E., Bains L., Baiocchi G. L., Bala M., Balague C., Balalis D., Baldini E., Baraket O., Baral S., Barone M., Barranquero A. G., Barreras J. A., Bass G. A., Bayhan Z., Bellanova G., Ben-Ishay O., Bert F., Bianchi V., Biancuzzi H., Bidoli C., Radulescu R. B., Bignell M. B., Biloslavo A., Bini R., Bissacco D., Boati P., Boddaert G., Bogdanic B., Bombardini C., Bonavina L., Bonomo L., Bottari A., Bouliaris K., Brachini G., Brillantino A., Brisinda G., Bulanauca M. M., Buonomo L. A., Burcharth J., Buscemi S., Calabretto F., Calini G., Calu V., Campanile F. C., Dall'Orto R. C., Campos-Serra A., Campostrini S., Capoglu R., Carvas J. M., Cascella M., Pattacini G. C., Celentano V., Centonze D. C., Ceresoli M., Chatzipetris D., Chessa A., Chiarello M. M., Chirica M., Chooklin S., Chouliaras C., Chowdhury S., Cianci P., Cillara N., Cimbanassi S., Cioffi S. P. B., Colak E., Ruiz E. C., Conti L., Coppola A., De Sa T. C., Costa S. D., Cozza V., Curro' G., Dabekaussen K. F. A. -S. A., D'acapito F., Damaskos D., D'ambrosio G., Das K., Davies R. J., De Beaux A. C., Fernandez S. P. L., De Luca A., De Stefano F., Degrate L., Demetrashvili Z., Demetriades A. K., Detanac D. S., Dezi A., Di Buono G., Di Carlo I., Di Lascio P., Di Martino M., Di Saverio S., Diaconescu B., Diaz J. J., Dibra R., Dimitrov E. N., Dinuzzi V. P., Dios-Barbeito S., Diyani J. F. A., Dogjani A., Domanin M., D'Oria M., Munoz-Cruzado V. D., East B., Ekelund M., Ekwen G. T., Elbaih A. H., Elhadi M., Enninghorst N., Ernisova M., Escalera-Antezana J. P., Esposito S., Esposito G., Estaire M., Fare C. N., Farre R., Favi F., Ferrario L., Vajana A. F. T., Filisetti C., Fleres F., Fonseca V. C., Forero-Torres A., Forfori F., Fortuna L., Fradelos E., Fraga G. P., Fransvea P., Frassini S., Frazzetta G., Pizzocaro E., Frountzas M., Gachabayov M., Galeiras R., Vazquez A. A. G., Gargarella S., Garzali I. U., Ghannam W. M., Ghazi F. N., Gillman L. M., Gioco R., Giordano A., Giordano L., Giove C., Giraudo G., Giuffrida M., Capponi M. G., Gois E., Gomes C. A., Gomes F. C., Gonsaga R. A. T., Gonullu E., Goosen J., Goranovic T., Gracia-Roman R., Graziano G. M. P., Griffiths E. A., Guagni T., Hadzhiev D. B., Haidar M. G., Hamid H. K. S., Hardcastle T. C., Hayati F., Healey A. J., Hecker A., Hecker M., Garcia E. F. H., Hodonou A. M., Huaman E. C., Huerta M., Ibrahim A. F., Ibrahim B. M. S., Ietto G., Inama M., Ioannidis O., Isik A., Ismail N., Ismail A. M. H., Jailani R. F., Jang J. Y., Kalfountzos C., Kalipershad S. N. R., Kaouras E., Kaplan L. J., Kara Y., Karamagioli E., Karamarkovia A., Katsaros I., Kavalakat A. J., Kechagias A., Kenig J., Kessel B. J., Khan J. S., Khokha V., Kim J. I., Kirkpatrick A. W., Klappenbach R., Kluger Y., Kobe Y., Lymperis E. K., Kok K. Y. Y., Kong V., Korkolis D. P., Koukoulis G., Kovacevic B., Kruger V. F., Kryvoruchko I. A., Kurihara H., Kuriyama A., Landaluce-Olavarria A., Lapolla P., Leppaniemi A., Licari L., Lisi G., Litvin A., Lizarazu A., Bayo H. L., Lohsiriwat V., Moreira C. C. L., Lostoridis E., Luna A. T., Luppi D., Machain V. G. M., Maegele M., Maggiore D., Magnone S., Maier R. V., Major P., Manangi M., Manetti A., Mantoglu B., Marafante C., Mariani F., Marinis A., Mariot E. A. S., Martines G., Perez A. M., Martino C., Mascagni P., Massalou D., Massaro M., Matias-Garcia B., Mazzarella G., Mazzarolo G., Melo R. B., Mendoza-Moreno F., Meric S., Meyer J., Miceli L., Michalopoulos N. V., Milana F., Mingoli A., Mishra T. S., Mohamed M., Mohamed M. I. E. A., Mohamedahmed A. Y., Mohammed M. J. S., Mohan R., Moore E. E., Morales-Garcia D., Muhrbeck M., Mulita F., Mustafa S. M. S., Muttillo E. M., Naimzada M. D., Navsaria P. H., Negoi I., Nespoli L., Nguyen C., Nidaw M. K., Nigri G., Nikolopoulos I., O'connor D. B., Ogundipe H. D., Oliveri C., Olmi S., Ong E. C. W., Orecchia L., Osipov A. V., Othman M. F., Pace M., Pacilli M., Pagani L., Palomba G., Pantalone D., Panyko A., Paolillo C., Papa M. V., Papaconstantinou D., Papadoliopoulou M., Papadopoulos A., Papis D., Pararas N., Parreira J. G., Parry N. G., Pata F., Patel T., Paterson-Brown S., Pavone G., Pecchini F., Pegoraro V., Pellino G., Pelloni M., Peloso A., Del Pozo E. P., Pereira R. G., Pereira B. M., Perez A. L., Perez S., Perra T., Perrone G., Pesce A., Petagna L., Petracca G., Phupong V., Picardi B., Picciariello A., Piccoli M., Picetti E., Pikoulis E. P., Pintar T., Pirozzolo G., Piscioneri F., Podda M., Porcu A., Privitera F., Punzo C., Quaresima S., Quiodettis M. A., Qvist N., Rahim R., de Almeida F. R., Ramely R. B., Rasa H. K., Reichert M., Reinisch-Liese A., Renne A., Riccetti C., Rodriguez-Luna M. R., Roizblatt D., Romanzi A., Romeo L., Roscio F. P. M., Rosnelifaizur R. B., Rossi S., Rubiano A. M., Ruiz-Ucar E., Sakakushev B. E., Salamea J. C., Sall I., Samarakoon L. B., Sammartano F., Arteaga A. S., Sanchez-Cordero S., Santoanastaso D. P. M., Sartelli M., Sasia D., Sato N., Savchuk A., Sawyer R. G., Scaioli G., Schizas D., Sebastiani S., Seeliger B., Lohse H. A. S., Seretis C., Sermonesi G., Serradilla-Martin M., Shelat V. G., Shlyapnikov S., Sidiropoulos T., Simoes R. L., Siragusa L., Siribumrungwong B., Slavchev M., Solaini L., Soldini G., Sopuev A., Soreide K., Sovatzidis A., Stahel P. F., Strickland M., Sultan M. A. H., Sydorchuk R., Sydorchuk L., Syed S. M. A. M., Tallon-Aguilar L., Tamburini A. M., Tamini N., Tan E. C. T. H., Tan J. H., Tarasconi A., Tartaglia N., Tartaglia G., Tartaglia D., Taylor J. V., Tebala G. D., Teuben M., Theodorou A., Tolonen M., Tomasicchio G., Toro A., Torre B., Triantafyllou T., Trigiante G. T., Tripepi M., Trostchansky J., Tsekouras K., Turrado-Rodriguez V., Tutino R., Uccelli M., Uchikov P. A., Ugarte-Sierra B., Ukkonen M. T., Vailas M., Vassiliu P. G., Vazquez A. G., Vazquez R. G., Velmahos G., Verde J. E., Verde J. M., Veroux M., Vigano J., Vilallonga R., Visconti D., Vittori A., Waledziak M., Wannatoop T., Widmer L. W., Wilson M. S. J., Woltz S., Wong T. H., Xenaki S., Yu B., Yule S., Zachariah S. K., Zacharis G., Zaghi C., Zakaria A. D., Zambrano D. A., Zampitis N., Zampogna B., Zanghi S., Zantedeschi M., Zapsalis K., Zattoni F., and Zese M.

Abstract

Background: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons’ preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI.

Published
2023

35. Pediatric trauma and emergency surgery: an international cross-sectional survey among WSES members

Author

Reichert, M, Sartelli, M, Askevold, I, Braun, J, Weigand, M, Hecker, M, Agnoletti, V, Coccolini, F, Catena, F, Padberg, W, Riedel, J, Hecker, A, Dogjani, A, Kuriyama, A, Porcu, A, Martinez-Perez, A, Coppola, A, Spolini, A, Giordano, A, Kyriakidis, A, Mohamedahmed, A, Vasilopoulou, A, Zakaria, A, Balla, A, Fette, A, Litvin, A, Guariniello, A, Isik, A, Kechagias, A, Mitul, A, De Simone, B, Zampogna, B, Sensi, B, Gazia, C, Seretis, C, Brooke, C, Luppi, D, Coletta, D, Sasia, D, Corallino, D, Chatzipetris, D, Schizas, D, Lostoridis, E, Hsabo, E, Kaouras, E, Schneck, E, Pinotti, E, Dimitrov, E, D'Acapito, F, Saraceno, F, Abu-Zidan, F, Silvestri, F, Favi, F, Fleres, F, Mulita, F, Nita, G, Martines, G, Mazzarella, G, Perrone, G, Giraudo, G, Bacchiocchi, G, Argenio, G, Brisinda, G, Curro, G, Palomba, G, Fraga, G, Hamid, H, Katsaros, I, Negoi, I, Tochie, J, Davies, J, Kok, K, Apostolou, K, Lasithiotakis, K, Tsekouras, K, Sydorchuk, L, Siragusa, L, Solaini, L, Ferrario, L, Buonomo, L, Waledziak, M, Gachabayov, M, Bulanauca, M, Agrawal, M, Ceresoli, M, Ranucci, M, Petridou, M, D'Oria, M, Veroux, M, Frountzas, M, Teuben, M, Bala, M, Minger, M, Goncalves, M, Sharma, N, Tamini, N, Medappil, N, Ioannidis, O, Bisagni, P, Rahim, R, Gonsaga, R, Ragozzino, R, Bini, R, Cammarata, R, Sydorchuk, R, Di Saverio, S, Awad, S, Atici, S, Meric, S, Chowdhury, S, Xenaki, S, Pintar, T, Perra, T, Hardcastle, T, Voglino, V, Lohsiriwat, V, Kong, V, Christos, V, Zuidema, W, Reichert M., Sartelli M., Askevold I. H., Braun J., Weigand M. A., Hecker M., Agnoletti V., Coccolini F., Catena F., Padberg W., Riedel J. G., Hecker A., Dogjani A., Kuriyama A., Porcu A., Martinez-Perez A., Coppola A., Spolini A., Giordano A., Kyriakidis A., Mohamedahmed A. Y. Y., Vasilopoulou A., Zakaria A. D., Balla A., Fette A., Litvin A., Guariniello A., Isik A., Kechagias A., Mitul A. R., De Simone B., Zampogna B., Sensi B., Gazia C., Seretis C., Brooke C., Luppi D., Coletta D., Sasia D., Corallino D., Chatzipetris D., Schizas D., Lostoridis E., Hsabo E. A., Kaouras E., Schneck E., Pinotti E., Dimitrov E., D'Acapito F., Saraceno F., Abu-Zidan F., Silvestri F. M., Favi F., Fleres F., Mulita F., Nita G., Martines G., Mazzarella G., Perrone G., Giraudo G., Bacchiocchi G., Argenio G., Brisinda G., Curro G., Palomba G., Fraga G. P., Hamid H. K. S., Katsaros I., Negoi I., Tochie J. N., Davies J., Kok K. Y. Y., Apostolou K. G., Lasithiotakis K., Tsekouras K., Sydorchuk L., Siragusa L., Solaini L., Ferrario L., Buonomo L., Waledziak M., Gachabayov M., Bulanauca M., Agrawal M. K., Ceresoli M., Ranucci M. C., Petridou M., D'Oria M., Veroux M., Frountzas M., Teuben M. P. J., Bala M., Minger M. A., Goncalves M., Sharma N., Tamini N., Medappil N., Ioannidis O., Bisagni P., Rahim R., Gonsaga R. A. T., Ragozzino R., Bini R., Cammarata R., Sydorchuk R., Di Saverio S., Awad S. S., Atici S. D., Meric S., Chowdhury S., Xenaki S., Pintar T., Perra T., Hardcastle T. C., Voglino V., Lohsiriwat V., Kong V., Christos V., Zuidema W., Reichert, M, Sartelli, M, Askevold, I, Braun, J, Weigand, M, Hecker, M, Agnoletti, V, Coccolini, F, Catena, F, Padberg, W, Riedel, J, Hecker, A, Dogjani, A, Kuriyama, A, Porcu, A, Martinez-Perez, A, Coppola, A, Spolini, A, Giordano, A, Kyriakidis, A, Mohamedahmed, A, Vasilopoulou, A, Zakaria, A, Balla, A, Fette, A, Litvin, A, Guariniello, A, Isik, A, Kechagias, A, Mitul, A, De Simone, B, Zampogna, B, Sensi, B, Gazia, C, Seretis, C, Brooke, C, Luppi, D, Coletta, D, Sasia, D, Corallino, D, Chatzipetris, D, Schizas, D, Lostoridis, E, Hsabo, E, Kaouras, E, Schneck, E, Pinotti, E, Dimitrov, E, D'Acapito, F, Saraceno, F, Abu-Zidan, F, Silvestri, F, Favi, F, Fleres, F, Mulita, F, Nita, G, Martines, G, Mazzarella, G, Perrone, G, Giraudo, G, Bacchiocchi, G, Argenio, G, Brisinda, G, Curro, G, Palomba, G, Fraga, G, Hamid, H, Katsaros, I, Negoi, I, Tochie, J, Davies, J, Kok, K, Apostolou, K, Lasithiotakis, K, Tsekouras, K, Sydorchuk, L, Siragusa, L, Solaini, L, Ferrario, L, Buonomo, L, Waledziak, M, Gachabayov, M, Bulanauca, M, Agrawal, M, Ceresoli, M, Ranucci, M, Petridou, M, D'Oria, M, Veroux, M, Frountzas, M, Teuben, M, Bala, M, Minger, M, Goncalves, M, Sharma, N, Tamini, N, Medappil, N, Ioannidis, O, Bisagni, P, Rahim, R, Gonsaga, R, Ragozzino, R, Bini, R, Cammarata, R, Sydorchuk, R, Di Saverio, S, Awad, S, Atici, S, Meric, S, Chowdhury, S, Xenaki, S, Pintar, T, Perra, T, Hardcastle, T, Voglino, V, Lohsiriwat, V, Kong, V, Christos, V, Zuidema, W, Reichert M., Sartelli M., Askevold I. H., Braun J., Weigand M. A., Hecker M., Agnoletti V., Coccolini F., Catena F., Padberg W., Riedel J. G., Hecker A., Dogjani A., Kuriyama A., Porcu A., Martinez-Perez A., Coppola A., Spolini A., Giordano A., Kyriakidis A., Mohamedahmed A. Y. Y., Vasilopoulou A., Zakaria A. D., Balla A., Fette A., Litvin A., Guariniello A., Isik A., Kechagias A., Mitul A. R., De Simone B., Zampogna B., Sensi B., Gazia C., Seretis C., Brooke C., Luppi D., Coletta D., Sasia D., Corallino D., Chatzipetris D., Schizas D., Lostoridis E., Hsabo E. A., Kaouras E., Schneck E., Pinotti E., Dimitrov E., D'Acapito F., Saraceno F., Abu-Zidan F., Silvestri F. M., Favi F., Fleres F., Mulita F., Nita G., Martines G., Mazzarella G., Perrone G., Giraudo G., Bacchiocchi G., Argenio G., Brisinda G., Curro G., Palomba G., Fraga G. P., Hamid H. K. S., Katsaros I., Negoi I., Tochie J. N., Davies J., Kok K. Y. Y., Apostolou K. G., Lasithiotakis K., Tsekouras K., Sydorchuk L., Siragusa L., Solaini L., Ferrario L., Buonomo L., Waledziak M., Gachabayov M., Bulanauca M., Agrawal M. K., Ceresoli M., Ranucci M. C., Petridou M., D'Oria M., Veroux M., Frountzas M., Teuben M. P. J., Bala M., Minger M. A., Goncalves M., Sharma N., Tamini N., Medappil N., Ioannidis O., Bisagni P., Rahim R., Gonsaga R. A. T., Ragozzino R., Bini R., Cammarata R., Sydorchuk R., Di Saverio S., Awad S. S., Atici S. D., Meric S., Chowdhury S., Xenaki S., Pintar T., Perra T., Hardcastle T. C., Voglino V., Lohsiriwat V., Kong V., Christos V., and Zuidema W.

Abstract

Background: In contrast to adults, the situation for pediatric trauma care from an international point of view and the global management of severely injured children remain rather unclear. The current study investigates structural management of pediatric trauma in centers of different trauma levels as well as experiences with pediatric trauma management around the world. Methods: A web-survey had been distributed to the global mailing list of the World Society of Emergency Surgery from 10/2021–03/2022, investigating characteristics of respondents and affiliated hospitals, case-load of pediatric trauma patients, capacities and infrastructure for critical care in children, trauma team composition, clinical work-up and individual experiences with pediatric trauma management in response to patients ́ age. The collaboration group was subdivided regarding sizes of affiliated hospitals to allow comparisons concerning hospital volumes. Comparable results were conducted to statistical analysis. Results: A total of 133 participants from 34 countries, i.e. 5 continents responded to the survey. They were most commonly affiliated with larger hospitals (> 500 beds in 72.9%) and with level I or II trauma centers (82.0%), respectively. 74.4% of hospitals offer unrestricted pediatric medical care, but only 63.2% and 42.9% of the participants had sufficient experiences with trauma care in children ≤ 10 and ≤ 5 years of age (p = 0.0014). This situation is aggravated in participants from smaller hospitals (p < 0.01). With regard to hospital size (≤ 500 versus > 500 in-hospital beds), larger hospitals were more likely affiliated with advanced trauma centers, more elaborated pediatric intensive care infrastructure (p < 0.0001), treated children at all ages more frequently (p = 0.0938) and have higher case-loads of severely injured children < 12 years of age (p = 0.0009). Therefore, the majority of larger hospitals reserve either pediatric surgery departments or board-certi

Published
2023

36. Time for a paradigm shift in shared decision-making in trauma and emergency surgery? Results from an international survey

Author

Cobianchi, L, Dal Mas, F, Agnoletti, V, Ansaloni, L, Biffl, W, Butturini, G, Campostrini, S, Catena, F, Denicolai, S, Fugazzola, P, Martellucci, J, Massaro, M, Previtali, P, Ruta, F, Venturi, A, Woltz, S, Kaafarani, H, Loftus, T, Aapoaylu, R, Abbott, K, Abdelmalik, A, Abebe, N, Abu-Zidan, F, Adam, Y, Adamou, H, Adamovich, D, Agresta, F, Agrusa, A, Akin, E, Alessiani, M, Alexandrino, H, Bidoli, C, Ali, S, Mihai, V, Almeida, P, Al-Shehari, M, Altomare, M, Amico, F, Ammendola, M, Andreuccetti, J, Anestiadou, E, Annicchiarico, A, Antonelli, A, Aparicio-Sanchez, D, Ardito, A, Argenio, G, Arvieux, C, Askevold, I, Atanasov, B, Augustin, G, Awad, S, Bacchiocchi, G, Bagnoli, C, Bahouth, H, Baili, E, Bains, L, Baiocchi, G, Bala, M, Balaguacopyright, C, Balalis, D, Baldini, E, Baraket, O, Baral, S, Barone, M, Gonzalez Barranquero, A, Barreras, J, Bass, G, Bayhan, Z, Bellanova, G, Ben-Ishay, O, Bert, F, Bianchi, V, Biancuzzi, H, Radulescu, R, Bignell, M, Biloslavo, A, Bini, R, Bissacco, D, Boati, P, Boddaert, G, Bogdanic, B, Bombardini, C, Bonavina, L, Bonomo, L, Bottari, A, Bouliaris, K, Brachini, G, Brillantino, A, Brisinda, G, Bulanauca, M, Buonomo, L, Burcharth, J, Buscemi, S, Calabretto, F, Calini, G, Calu, V, Campanile, F, Campo Dall'Orto, R, Campos-Serra, A, Carvas, J, Cascella, M, Pattacini, G, Celentano, V, Centonze, D, Ceresoli, M, Chatzipetris, D, Chessa, A, Chiarello, M, Chirica, M, Chooklin, S, Chouliaras, C, Chowdhury, S, Cianci, P, Cillara, N, Cimbanassi, S, Cioffi, S, Colais-Ruiz, E, Colak, E, Conti, L, Coppola, A, de Sa, T, Costa, S, Cozza, V, Curro', G, Dabekaussen, K, D'Acapito, F, Damaskos, D, D'Ambrosio, G, Das, K, Davies, R, de Beaux, A, De Lebrusant Fernandez, S, De Luca, A, De Simone, B, De Stefano, F, Degrate, L, Demetrashvili, Z, Demetriades, A, Detanac, D, Dezi, A, Di Buono, G, Carlo, I, Di Lascio, P, Di Martino, M, Di Saverio, S, Diaconescu, B, Diaz, J, Dibra, R, Dimitrov, E, Dinuzzi, V, Dios-Barbeito, S, Diyani, J, Dogjani, A, Domanin, M, D'Oria, M, Munoz-Cruzado, V, East, B, Ekelund, M, Ekwen, G, Elbaih, A, Elhadi, M, Enninghorst, N, Ernisova, M, Escalera-Antezana, J, Esposito, S, Esposito, G, Estaire-Gamez, M, Fara, C, Farre, R, Favi, F, Ferrario, L, Ferrario di Tor Vajana, A, Filisetti, C, Fleres, F, Fonseca, V, Forero-Torres, A, Forfori, F, Fortuna, L, Fradelos, E, Fraga, G, Fransvea, P, Frassini, S, Frazzetta, G, Frigerio, I, Frountzas, M, Gachabayov, M, Galeiras, R, Garcaa, B, Garcia Vazquez, A, Gargarella, S, Garzali, I, Ghannam, W, Ghazi, F, Gillman, L, Gioco, R, Giordano, A, Giordano, L, Giove, C, Giraudo, G, Giuffrida, M, Capponi, M, Gois, E, Gomes, C, Gomes, F, Gonsaga, R, Gonullu, E, Goosen, J, Goranovic, T, Gracia-Roman, R, Graziano, G, Griffiths, E, Guagni, T, Hadzhiev, D, Haidar, M, Hamid, H, Hardcastle, T, Hayati, F, Healey, A, Hecker, A, Hecker, M, Garcia, E, Hodonou, A, Huaman, E, Huerta, M, Ibrahim, A, Ibrahim, B, Ietto, G, Inama, M, Ioannidis, O, Isik, A, Ismail, N, Ismail, A, Jailani, R, Jang, J, Kalfountzos, C, Kalipershad, S, Kaouras, E, Kaplan, L, Kara, Y, Karamagioli, E, Karamarkovia, A, Katsaros, I, Kavalakat, A, Kechagias, A, Kenig, J, Kessel, B, Khan, J, Khokha, V, Kim, J, Kirkpatrick, A, Klappenbach, R, Kobe, Y, Lymperis, E, Kok, K, Kong, V, Korkolis, D, Koukoulis, G, Kovacevic, B, Kruger, V, Kryvoruchko, I, Kurihara, H, Kuriyama, A, Landaluce-Olavarria, A, Lapolla, P, Licari, L, Lisi, G, Litvin, A, Lizarazu, A, Bayo, H, Lohsiriwat, V, Moreira, C, Lostoridis, E, Luna, A, Luppi, D, V, G, Maegele, M, Maggiore, D, Magnone, S, Maier, R, Major, P, Manangi, M, Manetti, A, Mantoglu, B, Marafante, C, Mariani, F, Marinis, A, Mariot, E, Marseglia, G, Martanez-Parez, A, Martines, G, Perez, A, Martino, C, Mascagni, P, Massalou, D, Mataas-Garcaa, B, Mazzarella, G, Mazzarolo, G, Melo, R, Mendoza-Moreno, F, Meric, S, Meyer, J, Miceli, L, Michalopoulos, N, Milana, F, Mingoli, A, Mishra, T, Mohamed, M, Mohamedahmed, A, Mohammed, M, Mohan, R, Moore, E, Morales-Garcia, D, Muhrbeck, M, Mulita, F, Mustafa, S, Muttillo, E, Naimzada, M, Navsaria, P, Negoi, I, Nespoli, L, Nguyen, C, Nidaw, M, Nigri, G, Nikolopoulos, I, O'Connor, D, Ogundipe, H, Oliveri, C, Olmi, S, Ong, E, Orecchia, L, Osipov, A, Othman, M, Pace, M, Pacilli, M, Pagani, L, Palomba, G, Pantalone, D, Panyko, A, Paolillo, C, Papa, M, Papaconstantinou, D, Papadoliopoulou, M, Papadopoulos, A, Papis, D, Pararas, N, Parreira, J, Parry, N, Pata, F, Patel, T, Paterson-Brown, S, Pavone, G, Pecchini, F, Pellino, G, Pelloni, M, Peloso, A, del Pozo, E, Pereira, R, Pereira, B, Perra, T, Perrone, G, Pesce, A, Petagna, L, Petracca, G, Phupong, V, Picardi, B, Picciariello, A, Piccoli, M, Piccolo, D, Picetti, E, Pikoulis Pikoulis, E, Pintar, T, Pirozzolo, G, Piscioneri, F, Podda, M, Porcu, A, Privitera, F, Punzo, C, Quaresima, S, Quiodettis, M, Qvist, N, Rahim, R, de Almeida, F, Ramely, R, Rasa, H, Reichert, M, Reinisch-Liese, A, Renne, A, Riccetti, C, Rodriguez-Luna, M, Roizblatt, D, Romanzi, A, Romeo, L, Roscio, F, Rosnelifaizur, R, Rossi, S, Rubiano, A, Ruiz-Ascar, E, Sakakushev, B, Salamea, J, Sall, I, Samarakoon, L, Sammartano, F, Arteaga, A, Sanchez-Cordero, S, Santoanastaso, D, Sasia, D, Sato, N, Savchuk, A, Sawyer, R, Scaioli, G, Schizas, D, Sebastiani, S, Seeliger, B, Lohse, H, Seretis, C, Sermonesi, G, Serradilla-Martin, M, Shelat, V, Shlyapnikov, S, Sidiropoulos, T, Simoes, R, Siragusa, L, Siribumrungwong, B, Slavchev, M, Solaini, L, Soldini, G, Sopuev, A, Soreide, K, Sovatzidis, A, Stahel, P, Strickland, M, Sultan, M, Sydorchuk, R, Sydorchuk, L, Syed, S, Syed, A, Tallon-Aguilar, L, Tamburini, A, Tamini, N, Tan, E, Tan, J, Tarasconi, A, Tartaglia, N, Tartaglia, G, Tartaglia, D, Taylor, J, Tebala, G, Teuben, M, Theodorou, A, Tolonen, M, Tomasicchio, G, Toro, A, Torre, B, Triantafyllou, T, Trigiante Trigiante, G, Tripepi, M, Trostchansky, J, Tsekouras, K, Turrado-Rodriguez, V, Tutino, R, Uccelli, M, Uchikov, P, Ugarte-Sierra, B, Ukkonen, M, Vailas, M, Vassiliu, P, Vazquez, A, Vazquez, R, Verde, J, Veroux, M, Vigano, J, Vilallonga, R, Visconti, D, Vittori, A, Waledziak, M, Wannatoop, T, Widmer, L, Wilson, M, Wong, T, Xenaki, S, Yu, B, Yule, S, Zachariah, S, Zacharis, G, Zaghi, C, Zakaria, A, Zambrano, D, Zampitis, N, Zampogna, B, Zangha, S, Zapsalis, K, Zattoni, F, Zese, M, Farre, S, Pegoraro, V, Zantedeschi, M, Reitano, E, Pizzocaro, E, Cobianchi L., Dal Mas F., Agnoletti V., Ansaloni L., Biffl W., Butturini G., Campostrini S., Catena F., Denicolai S., Fugazzola P., Martellucci J., Massaro M., Previtali P., Ruta F., Venturi A., Woltz S., Kaafarani H. M., Loftus T. J., Aapoaylu R., Abbott K. L., Abdelmalik A., Abebe N. S., Abu-Zidan F., Adam Y. A. Y., Adamou H., Adamovich D. M., Agresta F., Agrusa A., Akin E., Alessiani M., Alexandrino H., Bidoli C., Ali S. M., Mihai V. A., Almeida P. M., Al-Shehari M. M., Altomare M., Amico F., Ammendola M., Andreuccetti J., Anestiadou E., Annicchiarico A., Antonelli A., Aparicio-Sanchez D., Ardito A., Argenio G., Arvieux C. C., Arvieux C., Askevold I. H., Atanasov B. T., Augustin G., Awad S. S., Bacchiocchi G., Bagnoli C., Bahouth H., Baili E., Bains L., Baiocchi G. L., Bala M., BalaguaCopyright C., Balalis D., Baldini E., Baraket O., Baral S., Barone M., Gonzalez Barranquero A., Barreras J. A., Bass G. A., Bayhan Z., Bellanova G., Ben-Ishay O., Bert F., Bianchi V., Biancuzzi H., Radulescu R. B., Bignell M. B., Biloslavo A., Bini R., Bissacco D., Boati P., Boddaert G., Bogdanic B., Bombardini C., Bonavina L., Bonomo L., Bottari A., Bouliaris K., Brachini G., Brillantino A., Brisinda G., Bulanauca M. M., Buonomo L. A., Burcharth J., Buscemi S., Calabretto F., Calini G., Calu V., Campanile F. C., Campo Dall'Orto R., Campos-Serra A., Carvas J. M., Cascella M., Pattacini G. C., Celentano V., Centonze D. C., Ceresoli M., Chatzipetris D., Chessa A., Chiarello M. M., Chirica M., Chooklin S., Chouliaras C., Chowdhury S., Cianci P., Cillara N., Cimbanassi S., Cioffi S. P. B., Colais-Ruiz E., Colak E., Conti L., Coppola A., de Sa T. C., Costa S. D., Cozza V., Curro' G., Dabekaussen K. F. A. -S. A., D'acapito F., Damaskos D., D'Ambrosio G., Das K., Davies R. J., de Beaux A. C., De Lebrusant Fernandez S. P., De Luca A., De Simone B., De Stefano F., Degrate L., Demetrashvili Z., Demetriades A. K., Detanac D. S., Dezi A., Di Buono G., Carlo I. -D. I., Di Lascio P., Di Martino M., Di Saverio S., Diaconescu B., Diaz J. J., Dibra R., Dimitrov E. N., Dinuzzi V. P., Dios-Barbeito S., Diyani J. F. A., Dogjani A., Domanin M., D'Oria M., Munoz-Cruzado V. D., East B., Ekelund M., Ekwen G. T., Elbaih A. H., Elhadi M., Enninghorst N., Ernisova M., Escalera-Antezana J. P., Esposito S., Esposito G., Estaire-Gamez M., Fara C. N., Farre R., Favi F., Ferrario L., Ferrario di Tor Vajana A., Filisetti C., Fleres F., Fonseca V. C., Forero-Torres A., Forfori F., Fortuna L., Fradelos E., Fraga G. P., Fransvea P., Frassini S., Frazzetta G., Frigerio I., Frountzas M., Gachabayov M., Galeiras R., Garcaa B. M., Garcia Vazquez A., Gargarella S., Garzali I. U., Ghannam W. M., Ghazi F. N., Gillman L. M., Gioco R., Giordano A., Giordano L., Giove C., Giraudo G., Giuffrida M., Capponi M. G., Gois E., Gomes C. A., Gomes F. C., Gonsaga R. A. T., Gonullu E., Goosen J., Goranovic T., Gracia-Roman R., Graziano G. M. P., Griffiths E. A., Guagni T., Hadzhiev D. B., Haidar M. G., Hamid H. K. S., Hardcastle T. C., Hayati F., Healey A. J., Hecker A., Hecker M., Garcia E. F. H., hodonou A. M., huaman E., Huerta M., Ibrahim A. F., Ibrahim B. M. S., Ietto G., Inama M., Ioannidis O., Isik A., Ismail N., Ismail A. M. H., Jailani R. F., Jang J. Y., Kalfountzos C., Kalipershad S. N. R., Kaouras E., Kaplan L. J., Kara Y., Karamagioli E., Karamarkovia A., Katsaros I., Kavalakat A. J., Kechagias A., Kenig J., Kessel B. J., Khan J. S., Khokha V., Kim J. I., Kirkpatrick A. W., Klappenbach R., Kobe Y., Lymperis E. K., Kok K. Y. Y., Kong V., Korkolis D. P., Koukoulis G., Kovacevic B., Kruger V. F., Kryvoruchko I. A., Kurihara H., Kuriyama A., Landaluce-Olavarria A., Lapolla P., Licari L., Lisi G., Litvin A., Lizarazu A., Bayo H. L., Lohsiriwat V., Moreira C. C. L., Lostoridis E., Luna A. T., Luppi D., V G. M. M., Maegele M., Maggiore D., Magnone S., Maier R. V., Major P., Manangi M., manetti A., Mantoglu B., Marafante C., Mariani F., Marinis A., Mariot E. A. S., Marseglia G. R., Martanez-Parez A., Martines G., Perez A. M., Martino C., Mascagni P., Massalou D., Mataas-Garcaa B., Mazzarella G., Mazzarolo G., Melo R. B., Mendoza-Moreno F., Meric S., Meyer J., Miceli L., Michalopoulos N. V., Milana F., Mingoli A., Mishra T. S., Mohamed M., Mohamed M. I. E. A., Mohamedahmed A. Y., Mohammed M. J. S., Mohan R., Moore E. E., Morales-Garcia D., Muhrbeck M., Mulita F., Mustafa S. M. S., Muttillo E. M., Naimzada M. D., Navsaria P. H., Negoi I., Nespoli L., Nguyen C., Nidaw M. K., Nigri G., Nikolopoulos I., O'Connor D. B., Ogundipe H. D., Oliveri C., Olmi S., Ong E. C. W., Orecchia L., Osipov A. V., Othman M. F., Pace M., Pacilli M., Pagani L., Palomba G., Pantalone D., Panyko A., Paolillo C., Papa M. V., Papaconstantinou D., Papadoliopoulou M., Papadopoulos A., Papis D., Pararas N., Parreira J. G., Parry N. G., Pata F., Patel T., Paterson-Brown S., Pavone G., Pecchini F., Pellino G., Pelloni M., Peloso A., del Pozo E. P., Pereira R. G., Pereira B. M., perez A. L., Perra T., Perrone G., Pesce A., Petagna L., Petracca G., Phupong V., Picardi B., Picciariello A., Piccoli M., Piccolo D., Picetti E., Pikoulis Pikoulis E., Pintar T., Pirozzolo G., Piscioneri F., Podda M., Porcu A., Privitera F., Punzo C., Quaresima S., Quiodettis M. A., Qvist N., Rahim R., de Almeida F. R., Ramely R. B., Rasa H. K., Reichert M., Reinisch-Liese A., Renne A., Riccetti C., Rodriguez-Luna M. R., Roizblatt D., Romanzi A., Romeo L., Roscio F. P. M., Rosnelifaizur R. B., Rossi S., Rubiano A. M., Ruiz-Ascar E., Sakakushev B. E., Salamea J. C., Sall I., Samarakoon L. B., Sammartano F., Arteaga A. S., Sanchez-Cordero S., Santoanastaso D. P. M., Sasia D., Sato N., Savchuk A., Sawyer R. G., Scaioli G., Schizas D., Sebastiani S., Seeliger B., Lohse H. A. S., Seretis C., Sermonesi G., Serradilla-Martin M., Shelat V. G., Shlyapnikov S., Sidiropoulos T., Simoes R. L., Siragusa L., Siribumrungwong B., Slavchev M., Solaini L., soldini G., Sopuev A., Soreide K., Sovatzidis A., Stahel P. F., Strickland M., Sultan M. A. H., Sydorchuk R., Sydorchuk L., Syed S. M. A. M., Syed A. M., Tallon-Aguilar L., Tamburini A. M., Tamini N., Tan E. C. T. H., Tan J. H., Tarasconi A., Tartaglia N., Tartaglia G., Tartaglia D., Taylor J. V., Tebala G. D., Teuben M., Theodorou A., Tolonen M., Tomasicchio G., Toro A., Torre B., Triantafyllou T., Trigiante Trigiante G., Tripepi M., Trostchansky J., Tsekouras K., Turrado-Rodriguez V., Tutino R., Uccelli M., Uchikov P. A., Ugarte-Sierra B., Ukkonen M. T., Vailas M., Vassiliu P. G., Vazquez A. G., Vazquez R. G., Verde J. E., Verde J. M., Veroux M., Vigano J., Vilallonga R., Visconti D., Vittori A., Waledziak M., Wannatoop T., Widmer L. W., Wilson M. S. J., Wong T. H., Xenaki S., Yu B., Yule S., Zachariah S. K., Zacharis G., Zaghi C., Zakaria A. D., Zambrano D. A., Zampitis N., Zampogna B., Zangha S., Zapsalis K., Zattoni F., Zese M., Farre S. P., Pegoraro V., Zantedeschi M., Reitano E., Pizzocaro E., Cobianchi, L, Dal Mas, F, Agnoletti, V, Ansaloni, L, Biffl, W, Butturini, G, Campostrini, S, Catena, F, Denicolai, S, Fugazzola, P, Martellucci, J, Massaro, M, Previtali, P, Ruta, F, Venturi, A, Woltz, S, Kaafarani, H, Loftus, T, Aapoaylu, R, Abbott, K, Abdelmalik, A, Abebe, N, Abu-Zidan, F, Adam, Y, Adamou, H, Adamovich, D, Agresta, F, Agrusa, A, Akin, E, Alessiani, M, Alexandrino, H, Bidoli, C, Ali, S, Mihai, V, Almeida, P, Al-Shehari, M, Altomare, M, Amico, F, Ammendola, M, Andreuccetti, J, Anestiadou, E, Annicchiarico, A, Antonelli, A, Aparicio-Sanchez, D, Ardito, A, Argenio, G, Arvieux, C, Askevold, I, Atanasov, B, Augustin, G, Awad, S, Bacchiocchi, G, Bagnoli, C, Bahouth, H, Baili, E, Bains, L, Baiocchi, G, Bala, M, Balaguacopyright, C, Balalis, D, Baldini, E, Baraket, O, Baral, S, Barone, M, Gonzalez Barranquero, A, Barreras, J, Bass, G, Bayhan, Z, Bellanova, G, Ben-Ishay, O, Bert, F, Bianchi, V, Biancuzzi, H, Radulescu, R, Bignell, M, Biloslavo, A, Bini, R, Bissacco, D, Boati, P, Boddaert, G, Bogdanic, B, Bombardini, C, Bonavina, L, Bonomo, L, Bottari, A, Bouliaris, K, Brachini, G, Brillantino, A, Brisinda, G, Bulanauca, M, Buonomo, L, Burcharth, J, Buscemi, S, Calabretto, F, Calini, G, Calu, V, Campanile, F, Campo Dall'Orto, R, Campos-Serra, A, Carvas, J, Cascella, M, Pattacini, G, Celentano, V, Centonze, D, Ceresoli, M, Chatzipetris, D, Chessa, A, Chiarello, M, Chirica, M, Chooklin, S, Chouliaras, C, Chowdhury, S, Cianci, P, Cillara, N, Cimbanassi, S, Cioffi, S, Colais-Ruiz, E, Colak, E, Conti, L, Coppola, A, de Sa, T, Costa, S, Cozza, V, Curro', G, Dabekaussen, K, D'Acapito, F, Damaskos, D, D'Ambrosio, G, Das, K, Davies, R, de Beaux, A, De Lebrusant Fernandez, S, De Luca, A, De Simone, B, De Stefano, F, Degrate, L, Demetrashvili, Z, Demetriades, A, Detanac, D, Dezi, A, Di Buono, G, Carlo, I, Di Lascio, P, Di Martino, M, Di Saverio, S, Diaconescu, B, Diaz, J, Dibra, R, Dimitrov, E, Dinuzzi, V, Dios-Barbeito, S, Diyani, J, Dogjani, A, Domanin, M, D'Oria, M, Munoz-Cruzado, V, East, B, Ekelund, M, Ekwen, G, Elbaih, A, Elhadi, M, Enninghorst, N, Ernisova, M, Escalera-Antezana, J, Esposito, S, Esposito, G, Estaire-Gamez, M, Fara, C, Farre, R, Favi, F, Ferrario, L, Ferrario di Tor Vajana, A, Filisetti, C, Fleres, F, Fonseca, V, Forero-Torres, A, Forfori, F, Fortuna, L, Fradelos, E, Fraga, G, Fransvea, P, Frassini, S, Frazzetta, G, Frigerio, I, Frountzas, M, Gachabayov, M, Galeiras, R, Garcaa, B, Garcia Vazquez, A, Gargarella, S, Garzali, I, Ghannam, W, Ghazi, F, Gillman, L, Gioco, R, Giordano, A, Giordano, L, Giove, C, Giraudo, G, Giuffrida, M, Capponi, M, Gois, E, Gomes, C, Gomes, F, Gonsaga, R, Gonullu, E, Goosen, J, Goranovic, T, Gracia-Roman, R, Graziano, G, Griffiths, E, Guagni, T, Hadzhiev, D, Haidar, M, Hamid, H, Hardcastle, T, Hayati, F, Healey, A, Hecker, A, Hecker, M, Garcia, E, Hodonou, A, Huaman, E, Huerta, M, Ibrahim, A, Ibrahim, B, Ietto, G, Inama, M, Ioannidis, O, Isik, A, Ismail, N, Ismail, A, Jailani, R, Jang, J, Kalfountzos, C, Kalipershad, S, Kaouras, E, Kaplan, L, Kara, Y, Karamagioli, E, Karamarkovia, A, Katsaros, I, Kavalakat, A, Kechagias, A, Kenig, J, Kessel, B, Khan, J, Khokha, V, Kim, J, Kirkpatrick, A, Klappenbach, R, Kobe, Y, Lymperis, E, Kok, K, Kong, V, Korkolis, D, Koukoulis, G, Kovacevic, B, Kruger, V, Kryvoruchko, I, Kurihara, H, Kuriyama, A, Landaluce-Olavarria, A, Lapolla, P, Licari, L, Lisi, G, Litvin, A, Lizarazu, A, Bayo, H, Lohsiriwat, V, Moreira, C, Lostoridis, E, Luna, A, Luppi, D, V, G, Maegele, M, Maggiore, D, Magnone, S, Maier, R, Major, P, Manangi, M, Manetti, A, Mantoglu, B, Marafante, C, Mariani, F, Marinis, A, Mariot, E, Marseglia, G, Martanez-Parez, A, Martines, G, Perez, A, Martino, C, Mascagni, P, Massalou, D, Mataas-Garcaa, B, Mazzarella, G, Mazzarolo, G, Melo, R, Mendoza-Moreno, F, Meric, S, Meyer, J, Miceli, L, Michalopoulos, N, Milana, F, Mingoli, A, Mishra, T, Mohamed, M, Mohamedahmed, A, Mohammed, M, 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M., Loftus T. J., Aapoaylu R., Abbott K. L., Abdelmalik A., Abebe N. S., Abu-Zidan F., Adam Y. A. Y., Adamou H., Adamovich D. M., Agresta F., Agrusa A., Akin E., Alessiani M., Alexandrino H., Bidoli C., Ali S. M., Mihai V. A., Almeida P. M., Al-Shehari M. M., Altomare M., Amico F., Ammendola M., Andreuccetti J., Anestiadou E., Annicchiarico A., Antonelli A., Aparicio-Sanchez D., Ardito A., Argenio G., Arvieux C. C., Arvieux C., Askevold I. H., Atanasov B. T., Augustin G., Awad S. S., Bacchiocchi G., Bagnoli C., Bahouth H., Baili E., Bains L., Baiocchi G. L., Bala M., BalaguaCopyright C., Balalis D., Baldini E., Baraket O., Baral S., Barone M., Gonzalez Barranquero A., Barreras J. A., Bass G. A., Bayhan Z., Bellanova G., Ben-Ishay O., Bert F., Bianchi V., Biancuzzi H., Radulescu R. B., Bignell M. B., Biloslavo A., Bini R., Bissacco D., Boati P., Boddaert G., Bogdanic B., Bombardini C., Bonavina L., Bonomo L., Bottari A., Bouliaris K., Brachini G., Brillantino A., Brisinda G., Bulanauca M. M., Buonomo L. A., Burcharth J., Buscemi S., Calabretto F., Calini G., Calu V., Campanile F. C., Campo Dall'Orto R., Campos-Serra A., Carvas J. M., Cascella M., Pattacini G. C., Celentano V., Centonze D. C., Ceresoli M., Chatzipetris D., Chessa A., Chiarello M. M., Chirica M., Chooklin S., Chouliaras C., Chowdhury S., Cianci P., Cillara N., Cimbanassi S., Cioffi S. P. B., Colais-Ruiz E., Colak E., Conti L., Coppola A., de Sa T. C., Costa S. D., Cozza V., Curro' G., Dabekaussen K. F. A. -S. A., D'acapito F., Damaskos D., D'Ambrosio G., Das K., Davies R. J., de Beaux A. C., De Lebrusant Fernandez S. P., De Luca A., De Simone B., De Stefano F., Degrate L., Demetrashvili Z., Demetriades A. K., Detanac D. S., Dezi A., Di Buono G., Carlo I. -D. I., Di Lascio P., Di Martino M., Di Saverio S., Diaconescu B., Diaz J. J., Dibra R., Dimitrov E. N., Dinuzzi V. P., Dios-Barbeito S., Diyani J. F. A., Dogjani A., Domanin M., D'Oria M., Munoz-Cruzado V. D., East B., Ekelund M., Ekwen G. T., Elbaih A. H., Elhadi M., Enninghorst N., Ernisova M., Escalera-Antezana J. P., Esposito S., Esposito G., Estaire-Gamez M., Fara C. N., Farre R., Favi F., Ferrario L., Ferrario di Tor Vajana A., Filisetti C., Fleres F., Fonseca V. C., Forero-Torres A., Forfori F., Fortuna L., Fradelos E., Fraga G. P., Fransvea P., Frassini S., Frazzetta G., Frigerio I., Frountzas M., Gachabayov M., Galeiras R., Garcaa B. M., Garcia Vazquez A., Gargarella S., Garzali I. U., Ghannam W. M., Ghazi F. N., Gillman L. M., Gioco R., Giordano A., Giordano L., Giove C., Giraudo G., Giuffrida M., Capponi M. G., Gois E., Gomes C. A., Gomes F. C., Gonsaga R. A. T., Gonullu E., Goosen J., Goranovic T., Gracia-Roman R., Graziano G. M. P., Griffiths E. A., Guagni T., Hadzhiev D. B., Haidar M. G., Hamid H. K. S., Hardcastle T. C., Hayati F., Healey A. J., Hecker A., Hecker M., Garcia E. F. H., hodonou A. M., huaman E., Huerta M., Ibrahim A. F., Ibrahim B. M. S., Ietto G., Inama M., Ioannidis O., Isik A., Ismail N., Ismail A. M. H., Jailani R. F., Jang J. Y., Kalfountzos C., Kalipershad S. N. R., Kaouras E., Kaplan L. J., Kara Y., Karamagioli E., Karamarkovia A., Katsaros I., Kavalakat A. J., Kechagias A., Kenig J., Kessel B. J., Khan J. S., Khokha V., Kim J. I., Kirkpatrick A. W., Klappenbach R., Kobe Y., Lymperis E. K., Kok K. Y. Y., Kong V., Korkolis D. P., Koukoulis G., Kovacevic B., Kruger V. F., Kryvoruchko I. A., Kurihara H., Kuriyama A., Landaluce-Olavarria A., Lapolla P., Licari L., Lisi G., Litvin A., Lizarazu A., Bayo H. L., Lohsiriwat V., Moreira C. C. L., Lostoridis E., Luna A. T., Luppi D., V G. M. M., Maegele M., Maggiore D., Magnone S., Maier R. V., Major P., Manangi M., manetti A., Mantoglu B., Marafante C., Mariani F., Marinis A., Mariot E. A. S., Marseglia G. R., Martanez-Parez A., Martines G., Perez A. M., Martino C., Mascagni P., Massalou D., Mataas-Garcaa B., Mazzarella G., Mazzarolo G., Melo R. B., Mendoza-Moreno F., Meric S., Meyer J., Miceli L., Michalopoulos N. V., Milana F., Mingoli A., Mishra T. S., Mohamed M., Mohamed M. I. E. A., Mohamedahmed A. Y., Mohammed M. J. S., Mohan R., Moore E. E., Morales-Garcia D., Muhrbeck M., Mulita F., Mustafa S. M. S., Muttillo E. M., Naimzada M. D., Navsaria P. H., Negoi I., Nespoli L., Nguyen C., Nidaw M. K., Nigri G., Nikolopoulos I., O'Connor D. B., Ogundipe H. D., Oliveri C., Olmi S., Ong E. C. W., Orecchia L., Osipov A. V., Othman M. F., Pace M., Pacilli M., Pagani L., Palomba G., Pantalone D., Panyko A., Paolillo C., Papa M. V., Papaconstantinou D., Papadoliopoulou M., Papadopoulos A., Papis D., Pararas N., Parreira J. G., Parry N. G., Pata F., Patel T., Paterson-Brown S., Pavone G., Pecchini F., Pellino G., Pelloni M., Peloso A., del Pozo E. P., Pereira R. G., Pereira B. M., perez A. L., Perra T., Perrone G., Pesce A., Petagna L., Petracca G., Phupong V., Picardi B., Picciariello A., Piccoli M., Piccolo D., Picetti E., Pikoulis Pikoulis E., Pintar T., Pirozzolo G., Piscioneri F., Podda M., Porcu A., Privitera F., Punzo C., Quaresima S., Quiodettis M. A., Qvist N., Rahim R., de Almeida F. R., Ramely R. B., Rasa H. K., Reichert M., Reinisch-Liese A., Renne A., Riccetti C., Rodriguez-Luna M. R., Roizblatt D., Romanzi A., Romeo L., Roscio F. P. M., Rosnelifaizur R. B., Rossi S., Rubiano A. M., Ruiz-Ascar E., Sakakushev B. E., Salamea J. C., Sall I., Samarakoon L. B., Sammartano F., Arteaga A. S., Sanchez-Cordero S., Santoanastaso D. P. M., Sasia D., Sato N., Savchuk A., Sawyer R. G., Scaioli G., Schizas D., Sebastiani S., Seeliger B., Lohse H. A. S., Seretis C., Sermonesi G., Serradilla-Martin M., Shelat V. G., Shlyapnikov S., Sidiropoulos T., Simoes R. L., Siragusa L., Siribumrungwong B., Slavchev M., Solaini L., soldini G., Sopuev A., Soreide K., Sovatzidis A., Stahel P. F., Strickland M., Sultan M. A. H., Sydorchuk R., Sydorchuk L., Syed S. M. A. M., Syed A. M., Tallon-Aguilar L., Tamburini A. M., Tamini N., Tan E. C. T. H., Tan J. H., Tarasconi A., Tartaglia N., Tartaglia G., Tartaglia D., Taylor J. V., Tebala G. D., Teuben M., Theodorou A., Tolonen M., Tomasicchio G., Toro A., Torre B., Triantafyllou T., Trigiante Trigiante G., Tripepi M., Trostchansky J., Tsekouras K., Turrado-Rodriguez V., Tutino R., Uccelli M., Uchikov P. A., Ugarte-Sierra B., Ukkonen M. T., Vailas M., Vassiliu P. G., Vazquez A. G., Vazquez R. G., Verde J. E., Verde J. M., Veroux M., Vigano J., Vilallonga R., Visconti D., Vittori A., Waledziak M., Wannatoop T., Widmer L. W., Wilson M. S. J., Wong T. H., Xenaki S., Yu B., Yule S., Zachariah S. K., Zacharis G., Zaghi C., Zakaria A. D., Zambrano D. A., Zampitis N., Zampogna B., Zangha S., Zapsalis K., Zattoni F., Zese M., Farre S. P., Pegoraro V., Zantedeschi M., Reitano E., and Pizzocaro E.

Abstract

Background: Shared decision-making (SDM) between clinicians and patients is one of the pillars of the modern patient-centric philosophy of care. This study aims to explore SDM in the discipline of trauma and emergency surgery, investigating its interpretation as well as the barriers and facilitators for its implementation among surgeons. Methods: Grounding on the literature on the topics of the understanding, barriers, and facilitators of SDM in trauma and emergency surgery, a survey was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was sent to all 917 WSES members, advertised through the society’s website, and shared on the society’s Twitter profile. Results: A total of 650 trauma and emergency surgeons from 71 countries in five continents participated in the initiative. Less than half of the surgeons understood SDM, and 30% still saw the value in exclusively engaging multidisciplinary provider teams without involving the patient. Several barriers to effectively partnering with the patient in the decision-making process were identified, such as the lack of time and the need to concentrate on making medical teams work smoothly. Discussion: Our investigation underlines how only a minority of trauma and emergency surgeons understand SDM, and perhaps, the value of SDM is not fully accepted in trauma and emergency situations. The inclusion of SDM practices in clinical guidelines may represent the most feasible and advocated solutions.

Published
2023

37. High-Risk Neuroblastoma Challenges and Opportunities for Antibody-Based Cellular Immunotherapy.

Author

Persaud, Natasha V., Park, Jeong A., and Cheung, Nai Kong V.

Subjects
SYMPATHETIC nervous system, BISPECIFIC antibodies, CELL surface antigens, NEURAL crest, TUMOR antigens, NEUROBLASTOMA
Abstract

Immunotherapy has emerged as an attractive option for patients with relapsed or refractory high-risk neuroblastoma (HRNB). Neuroblastoma (NB), a sympathetic nervous system cancer arising from an embryonic neural crest cell, is heterogeneous clinically, with outcomes ranging from an isolated abdominal mass that spontaneously regresses to a widely metastatic disease with cure rates of about 50% despite intensive multimodal treatment. Risk group stratification and stage-adapted therapy to achieve cure with minimal toxicities have accomplished major milestones. Targeted immunotherapeutic approaches including monoclonal antibodies, vaccines, adoptive cellular therapies, their combinations, and their integration into standard of care are attractive therapeutic options, although curative challenges and toxicity concerns remain. In this review, we provide an overview of immune approaches to NB and the tumor microenvironment (TME) within the clinical translational framework. We propose a novel T cell-based therapeutic approach that leverages the unique properties of tumor surface antigens such as ganglioside GD2, incorporating specific monoclonal antibodies and recent advancements in adoptive cell therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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41. T cell engaging bispecific antibodies targeting CD33 IgV and IgC domains for the treatment of acute myeloid leukemia

Author

Madelyn Espinosa-Cotton, Sayed Shahabuddin Hoseini, Hong-fen Guo, Nai-Kong V Cheung, Yi Feng, Mallika Vadlamudi, Hoa Tran, and Irene Cheung

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

Background Acute myeloid leukemia (AML) remains one of the most challenging hematological malignancies. Despite progress in therapeutics, majority of patients succumb to this neoplasm. CD33 is a proven therapeutic target, given its expression on most AML cells. Almost all anti-CD33 antibodies target the membrane distal immunoglobulin V (IgV) domain of the CD33 extracellular domain.Methods In this manuscript, we present data on three bispecific antibodies (BsAbs) against the CD33 IgV and membrane proximal immunoglobulin C (IgC) domains. We use in vitro binding and cytotoxicity assays to show the effect of these BsAbs on AML cell lines. We also use immunodeficient mice-bearing leukemias from cell lines and patient-derived xenografts to show the effect of these BsAbs in vivo.Results In vitro, the IgV-targeting BsAb had higher binding to AML cell lines using flow cytometry and delivered more potent cytotoxicity in T-cell-dependent cytotoxicity assays; importantly, the IgC domain-targeting outperformed the IgV domain-targeting BsAb in medullary and extramedullary leukemia animal models.Conclusions These data support further clinical development of this BsAb for first-in-human phase I clinical trial.

Published
2021
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45. A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy

Author

Hong Xu, Ilia N. Buhtoiarov, Hongfen Guo, and Nai-Kong V. Cheung

Subjects
il15, il15rα, hu3f8, bispecific antibody, immunotherapy, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The role of T cells in controlling human cancers is well known. Their success requires continued persistence in vivo and efficient trafficking to tumor sites, requirements shared by other effectors such as Natural Killer (NK) cells. To date, cytokine IL2 remains the only clinically approved cytokine therapy available to expand, maintain, and activate these effector lymphoid cells, but toxicities can be severe. Cytokine IL15 offers similar T cell proliferation and activation properties, but without the unwanted side-effects seen with IL2. Several IL15-cytokine fusion proteins have been developed to improve their in vivo function, typically exploiting the IL15Rα to complex with IL15, to extend serum half-life and increase affinity for IL15β receptor on immune cells. Here we describe a novel IL15 complex incorporating the full-length IL15Rα to complex with wild type IL15 to form spontaneous trimers of dimers (6 IL15 + 6 IL15Rα) during co-expression, resulting in a substantial increase in serum half-life and enhancement of in vivo cytokine effect on IgG or T cell engaging antibody-dependent cell-mediated cytotoxicities, when compared to alternative strategies.

Published
2021
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47. Overcoming leukemia heterogeneity by combining T cell engaging bispecific antibodies

Author

Madelyn Espinosa-Cotton, Sayed Shahabuddin Hoseini, Hong-fen Guo, and Nai-Kong V Cheung

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

Background Leukemia represents about 5% of all human cancers. Despite advances in therapeutics, a substantial number of patients succumb to the disease. Several subtypes of leukemia are inherently more resistant to treatment despite intensive chemotherapy or targeted therapy.Methods Here we describe the generation of T cell engaging (CD3) bispecific antibodies (BsAbs) built on humanized IgG frameworks using the IgG(L)-scFv format against two targets expressed on acute lymphoblastic leukemia (ALL) and on acute myeloid leukemia (AML).Results Each BsAb mediated potent anti-leukemia effect against ALL (CD19) and AML (CD33) in vitro and in xenograft models. Importantly, the CD19-specific BsAb (BC250) was effective against hematogenous spread preventing metastases to liver and kidney in mice bearing ALL and Burkitt’s lymphoma xenografts. BC250 was more potent than the The Food and Drug Administration (FDA)-approved BsAb blinatumomab against ALL xenografts in vivo as measured by tumor bioluminescence and mouse survival. Furthermore, the combination of the CD19 and CD33 BsAbs in two xenograft models of mixed phenotype acute leukemia (biphenotypic and bilineal leukemia) was far superior than monotherapy with either of the BsAbs alone.Conclusions Selective combinations of these leukemia-specific BsAb offer the potential to overcome tumor heterogeneity or clonal escape in the modern era of antibody-based T cell-driven immunotherapy.

Published
2020
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