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Article: Outcomes of Surgical Treatment for Extradural Benign Primary Spinal Tumors in Patients Younger than 25 Years: An Ambispective International Multicenter Study.

Disch, Alexander C / Boriani, Stefano / Lazary, Aron / Rhines, Laurence D / Luzzati, Alessandro / Gokaslan, Ziya L / Fisher, Charles G / Fehlings, Michael G / Clarke, Michelle J / Chou, Dean / Germscheid, Nicole M / Schaser, Klaus-Dieter / Reynolds, Jeremy J / The Ao Spine Knowledge Forum Tumor

Cancers

2023 Volume 15, Issue 3

Abstract: Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were ... ...

Abstract	Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were identified. Patient- and case-related characteristics were collected and statistically analyzed. Results: 161 patients (66f;95m; age 17.0 ± 4.7 years at time of diagnosis) were identified. The most common tumors were osteoblastomas
Language	English
Publishing date	2023-01-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030650
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Article: Extradural Primary Malignant Spinal Tumors in a Population Younger than 25 Years: An Ambispective International Multicenter Study on Onco-Surgical Outcomes.

Disch, Alexander C / Boriani, Stefano / Luzzati, Alessandro / Rhines, Laurence D / Fisher, Charles G / Lazary, Aron / Gokaslan, Ziya L / Chou, Dean / Clarke, Michelle J / Fehlings, Michael G / Schaser, Klaus-Dieter / Germscheid, Nicole M / Reynolds, Jeremy J / The Ao Spine Knowledge Forum Tumor

Cancers

2023 Volume 15, Issue 3

Abstract: Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ... ...

Abstract	Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ClinicalTrials.gov Identifier NCT01643174) by the AO Spine Knowledge Forum Tumor, patients surgically treated for primary tumors of the spine between 1992 and 2012, were retrospectively analyzed from a prospective database of their medical history. Medical history, tumor characteristics, diagnostics, treatments, cross-sectional survival, and local recurrences were analyzed. Sixty-eight cases (32 f; 36 m), at an average age of 18.6 ± 4.7 years at the time of diagnosis, were identified (median follow-up 2.9 years). The most common entities were Ewing's sarcoma (42.6%). Of the patients, 28% had undergone previous spine tumor surgery in another center (84% with intralesional margins). Resection was considered "Enneking appropriate" (EA) in 47.8% of the cases. Of the patients, 77.9% underwent chemotherapy and 50% radiotherapy. A local recurrence occurred in 36.4%. Over a third of patients died within a 10-year follow-up period. Kaplan-Meier-analysis demonstrated statistically significant overall survival (
Language	English
Publishing date	2023-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030845
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Article ; Online: Using the singular value decomposition to extract 2D correlation functions from scattering patterns.

Bender, Philipp / Zákutná, Dominika / Disch, Sabrina / Marcano, Lourdes / Alba Venero, Diego / Honecker, Dirk

Acta crystallographica. Section A, Foundations and advances

2019 Volume 75, Issue Pt 5, Page(s) 766–771

Abstract: The truncated singular value decomposition (TSVD) is applied to extract the underlying 2D correlation functions from small-angle scattering patterns. The approach is tested by transforming the simulated data of ellipsoidal particles and it is shown that ... ...

Abstract	The truncated singular value decomposition (TSVD) is applied to extract the underlying 2D correlation functions from small-angle scattering patterns. The approach is tested by transforming the simulated data of ellipsoidal particles and it is shown that also in the case of anisotropic patterns (i.e. aligned ellipsoids) the derived correlation functions correspond to the theoretically predicted profiles. Furthermore, the TSVD is used to analyze the small-angle X-ray scattering patterns of colloidal dispersions of hematite spindles and magnetotactic bacteria in the presence of magnetic fields, to verify that this approach can be applied to extract model-free the scattering profiles of anisotropic scatterers from noisy data.
MeSH term(s)	Anisotropy ; Colloids ; Ferric Compounds/chemistry ; Magnetic Fields ; Magnetospirillum/chemistry ; Scattering, Small Angle ; X-Ray Diffraction/statistics & numerical data
Chemical Substances	Colloids ; Ferric Compounds ; ferric oxide (1K09F3G675)
Language	English
Publishing date	2019-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2020844-3
ISSN	2053-2733 ; 1600-5724 ; 0108-7673
ISSN (online)	2053-2733 ; 1600-5724
ISSN	0108-7673
DOI	10.1107/S205327331900891X
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Article ; Online: Perception of frailty in spinal metastatic disease: international survey of the AO Spine community.

Journal of neurosurgery. Spine

2023 , Page(s) 1–11

Abstract: Objective: Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess ... ...

Abstract	Objective: Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess frailty in SMD. Methods: The AO Spine Knowledge Forum Tumor conducted an international cross-sectional survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to capture preoperative surrogate markers of frailty and relevant postoperative clinical outcomes in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. Results: Results were analyzed for 359 respondents, with an 87% completion rate. Study participants represented 71 countries. In the clinical setting, most respondents informally assess frailty and cognition in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained among respondents regarding the association between 14 preoperative clinical variables and frailty. Severe comorbidities, extensive systemic disease burden, and poor performance status were most associated with frailty. Severe comorbidities associated with frailty included high-risk cardiopulmonary disease, renal failure, liver failure, and malnutrition. The most clinically relevant outcomes were major complications, neurological recovery, and change in performance status. Conclusions: The respondents recognized that frailty is important, but they most commonly evaluate it based on general clinical impressions rather than using existing frailty tools. The authors identified numerous preoperative surrogate markers of frailty and postoperative clinical outcomes that spine surgeons perceived as most relevant in this population.
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2158643-3
ISSN	1547-5646 ; 1547-5654
ISSN (online)	1547-5646
ISSN	1547-5654
DOI	10.3171/2023.1.SPINE221433
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Article: Evaluation of an Injectable Biphasic Calcium Sulfate/Hydroxyapatite Cement for the Augmentation of Fenestrated Pedicle Screws in Osteoporotic Vertebrae: A Biomechanical Cadaver Study.

Tian, Xinggui / Raina, Deepak B / Vater, Corina / Kilian, David / Ahlfeld, Tilman / Platzek, Ivan / Nimtschke, Ute / Tägil, Magnus / Lidgren, Lars / Thomas, Alexander / Platz, Uwe / Schaser, Klaus-Dieter / Disch, Alexander C / Zwingenberger, Stefan

Journal of functional biomaterials

2022 Volume 13, Issue 4

Abstract: Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate ... ...

Abstract	Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an injectable, bioactive, and degradable calcium sulfate/hydroxyapatite (CaS/HA) cement could increase the maximum pull-out force of pedicle screws in osteoporotic vertebrae. Herein, 17 osteoporotic thoracic and lumbar vertebrae were obtained from a single fresh-frozen human cadaver and instrumented with fenestrated pedicle screws. The right screw in each vertebra was augmented with CaS/HA cement and the un-augmented left side served as a paired control. The cement distribution, interdigitation ability, and cement leakage were evaluated using radiographs. Furthermore, pull-out testing was used to evaluate the immediate mechanical effect of CaS/HA augmentation on the pedicle screws. The CaS/HA cement presented good distribution and interdigitation ability without leakage into the spinal canal. Augmentation significantly enhanced the maximum pull-out force of the pedicle screw in which the augmented side was 39.0% higher than the pedicle-screw-alone side. Therefore, the novel biodegradable biphasic CaS/HA cement could be a promising material for pedicle screw augmentation in the osteoporotic spine.
Language	English
Publishing date	2022-12-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2648525-4
ISSN	2079-4983
ISSN	2079-4983
DOI	10.3390/jfb13040269
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Article ; Online: Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.

Ramos, Ashley L / Goedken, Eric R / Frank, Kristine E / Argiriadi, Maria A / Bazzaz, Sana / Bian, Zhiguo / Brown, Jesse T C / Centrella, Paolo A / Chen, Hui-Ju / Disch, Jeremy S / Donner, Pamela L / Duignan, David B / Gikunju, Diana / Greszler, Stephen N / Guié, Marie-Aude / Habeshian, Sevan / Hartl, Hajnalka E / Hein, Christopher D / Hutchins, Charles W /

Journal of medicinal chemistry

2024 Volume 67, Issue 8, Page(s) 6456–6494

Abstract: Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule ...

Abstract	Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.
MeSH term(s)	Interleukin-17/metabolism ; Interleukin-17/antagonists & inhibitors ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; DNA/metabolism ; DNA/chemistry ; Humans ; Drug Discovery ; Animals ; Structure-Activity Relationship ; Protein Binding ; Mice
Chemical Substances	Interleukin-17 ; Small Molecule Libraries ; DNA (9007-49-2) ; IL17A protein, human
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c02397
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Conference proceedings: Calcium sulfate/hydroxyapatite mediated controlled co-delivery of BMP-2 and zoledronic acid enhances spinal fusion in a rat posterolateral spinal fusion model

Tian, Xinggui / Vater, Corina / Raina, Deepak / Findeisen, Lisa / Matuszewski, Lucas-Maximilian / Tägil, Magnus / Lidgren, Lars / Schaser, Klaus-Dieter / Disch, Alexander C. / Zwingenberger, Stefan

2023 , Page(s) AB54–2784

Event/congress	Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2023); Berlin; ; Berufsverband für Orthopädie und Unfallchirurgie; 2023
Keywords	Medizin, Gesundheit ; BMP-2 ; zoledronic acid ; posterolateral lumbar fusion ; spine
Publishing date	2023-10-23
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/23dkou263
Database	German Medical Science

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Article ; Online: Discovery of Nanomolar DCAF1 Small Molecule Ligands.

Li, Alice Shi Ming / Kimani, Serah / Wilson, Brian / Noureldin, Mahmoud / González-Álvarez, Héctor / Mamai, Ahmed / Hoffer, Laurent / Guilinger, John P / Zhang, Ying / von Rechenberg, Moritz / Disch, Jeremy S / Mulhern, Christopher J / Slakman, Belinda L / Cuozzo, John W / Dong, Aiping / Poda, Gennady / Mohammed, Mohammed / Saraon, Punit / Mittal, Manish /

Modh, Pratik / Rathod, Vaibhavi / Patel, Bhashant / Ackloo, Suzanne / Santhakumar, Vijayaratnam / Szewczyk, Magdalena M / Barsyte-Lovejoy, Dalia / Arrowsmith, Cheryl H / Marcellus, Richard / Guié, Marie-Aude / Keefe, Anthony D / Brown, Peter J / Halabelian, Levon / Al-Awar, Rima / Vedadi, Masoud

Journal of medicinal chemistry

2023 Volume 66, Issue 7, Page(s) 5041–5060

Abstract: DCAF1 is a substrate receptor of two distinct E3 ligases ( ... ...

Abstract	DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4
MeSH term(s)	Humans ; Ligands ; Ubiquitin-Protein Ligases/metabolism ; Carrier Proteins/chemistry ; Neoplasms
Chemical Substances	Ligands ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Carrier Proteins
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c02132
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Conference proceedings: A novel selective prostaglandin-receptor EP4-agonist promotes posterolateral spinal fusion in a rat model

Zwingenberger, Stefan / Tian, Xinggui / Findeisen, Lisa / Raina, Deepak / Kern, Hannes / Bolte, Julia / Modler, Niels / Winkler, Anja / Gottwald, Robert / Schaser, Klaus-Dieter / Disch, Alexander C. / Vater, Corina

2023 , Page(s) AB71–2780

Event/congress	Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2023); Berlin; ; Berufsverband für Orthopädie und Unfallchirurgie; 2023
Keywords	Medizin, Gesundheit ; spinal fusion ; bone regeneration ; prostaglandin agonist ; EP4 receptor
Publishing date	2023-10-23
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/23dkou362
Database	German Medical Science

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Article ; Online: Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient.

Nature communications

2023 Volume 14, Issue 1, Page(s) 1999

Abstract: Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb ... ...

Abstract	Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patient with hypogammaglobulinemia. Following mAb treatment, the patient did not clear the infection. During viral persistence, SARS-CoV-2 acquired three novel spike mutations. Neutralization and mouse protection analyses demonstrate a complete viral escape from REGN-COV at the expense of ACE-2 binding. Final clearance of the virus occurred upon reduction of the immunosuppressive regimen and total IgG substitution. Serology suggests that the development of highly neutralizing IgM rather than IgG substitution aids clearance. Our findings emphasise that selection pressure by mAbs on SARS-CoV-2 can lead to development of escape variants in immunocompromised patients. Thus, modification of immunosuppressive therapy, if possible, might be preferable to control and clearance of the viral infection.
MeSH term(s)	Animals ; Mice ; SARS-CoV-2 ; Antibodies, Viral ; Neutralization Tests ; COVID-19 ; Antibodies, Neutralizing ; Immunocompromised Host ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-04-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37591-w
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