27 results on '"Markus, Wiedmann"'
Search Results
2. Early Career Bypass surgery for intracranial aneurysms in the endovascular era: A case series
- Author
-
Markus Wiedmann
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2023
- Full Text
- View/download PDF
Catalog
3. Metabolic Factors, Life-style and Risk for Meningioma in Women: Results from the Cohort of Norway (CONOR)
- Author
-
Ana Gheorghiu, Cathrine Brunborg, Tom Børge Johannesen, John Anker Zwart, Eirik Helseth, and Markus Wiedmann
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2023
- Full Text
- View/download PDF
4. Real time intraoperative indocyanine green (ICG) for endoscopic transsphenoidal resection of ACTH-secreting pituitary adenomas: A case series
- Author
-
Markus Wiedmann, Ida Olesrud, Ansgar Heck, and Daniel Dahlberg
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2023
- Full Text
- View/download PDF
5. Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series
- Author
-
Markus Wiedmann, Thor Skattør, Arne Stray-Pedersen, Luis Romundstad, Ellen-Ann Antal, Pål Bache Marthinsen, Ingvild Hausberg Sørvoll, Siw Leiknes Ernstsen, Christian G. Lund, Pål Andre Holme, Tonje Okkenhaug Johansen, Cathrine Brunborg, Anne Hege Aamodt, Nina Haagenrud Schultz, Karolina Skagen, and Mona Skjelland more...
- Subjects
COVID-19 ,SARS-CoV-2 virus ,sinus vein thrombosis ,thrombocytopenia ,cerebral venous thrombosis ,complication ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1–2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate. more...
- Published
- 2021
- Full Text
- View/download PDF
6. Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination
- Author
-
Adrian Scutelnic, Katarzyna Krzywicka, Joshua Mbroh, Anita van de Munckhof, Mayte Sánchez van Kammen, Diana Aguiar de Sousa, Erik Lindgren, Katarina Jood, Albrecht Günther, Sini Hiltunen, Jukka Putaala, Andreas Tiede, Frank Maier, Rolf Kern, Thorsten Bartsch, Katharina Althaus, Alfonso Ciccone, Markus Wiedmann, Mona Skjelland, Antonio Medina, Elisa Cuadrado‐Godia, Thomas Cox, Avinash Aujayeb, Nicolas Raposo, Katia Garambois, Jean‐Francois Payen, Fabrice Vuillier, Guillaume Franchineau, Serge Timsit, David Bougon, Marie‐Cécile Dubois, Audrey Tawa, Clement Tracol, Emmanuel De Maistre, Fabrice Bonneville, Caroline Vayne, Annerose Mengel, Dominik Michalski, Johann Pelz, Matthias Wittstock, Felix Bode, Julian Zimmermann, Judith Schouten, Alina Buture, Sean Murphy, Vincenzo Palma, Alberto Negro, Alexander Gutschalk, Simon Nagel, Silvia Schoenenberger, Giovanni Frisullo, Carla Zanferrari, Francesco Grillo, Fabrizio Giammello, Mar Morin Martin, Alvaro Cervera, Jim Burrow, Carlos Garcia Esperon, Beng Lim Alvin Chew, Timothy J. Kleinig, Cristina Soriano, Domenico S. Zimatore, Marco Petruzzellis, Ahmed Elkady, Miguel S. Miranda, João Fernandes, Åslög Hellström Vogel, Elias Johansson, Anemon Puthuppallil Philip, Shelagh B. Coutts, Simerpreet Bal, Brian Buck, Catherine Legault, Dylan Blacquiere, Hans D. Katzberg, Thalia S. Field, Vanessa Dizonno, Thomas Gattringer, Christian Jacobi, Annemie Devroye, Robin Lemmens, Espen Saxhaug Kristoffersen, Monica Bandettini di Poggio, Masoud Ghiasian, Theodoros Karapanayiotides, Sophie Chatterton, Miriam Wronski, Karl Ng, Robert Kahnis, Thomas Geeraerts, Peggy Reiner, Charlotte Cordonnier, Saskia Middeldorp, Marcel Levi, Eric C. M. van Gorp, Diederik van de Beek, Justine Brodard, Johanna A. Kremer Hovinga, Marieke J. H. A. Kruip, Turgut Tatlisumak, José M. Ferro, Jonathan M. Coutinho, Marcel Arnold, Sven Poli, Mirjam R. Heldner, Virology, Hematology, HUS Neurocenter, Department of Neurosciences, University of Helsinki, Neurologian yksikkö, Clinicum, Neurology, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ANS - Neuroinfection & -inflammation, AII - Infectious diseases, and Repositório da Universidade de Lisboa more...
- Subjects
SINUS THROMBOSIS ,Venous Thrombosis ,COVID-19 Vaccines ,SARS-CoV-2 ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Vaccination ,3112 Neurosciences ,Embòlia i trombosi cerebral ,Anticoagulants ,COVID-19 ,Immunoglobulins, Intravenous ,610 Medicine & health ,Hematology ,Vacunes ,COVID-19 (Malaltia) ,3124 Neurology and psychiatry ,Adenoviridae ,Neurology ,SDG 3 - Good Health and Well-being ,Humans ,Hematologi ,Neurology (clinical) ,Intracranial Thrombosis - Abstract
© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation. more...
- Published
- 2022
- Full Text
- View/download PDF
7. Re-evaluation of MRI in the follow-up of acromegaly - a path towards long-term remission?
- Author
-
Shahriar Atai, Martin Knudtzon Andersen, Jens Bollerslev, Daniel Dahlberg, Markus Wiedmann, Geir Andre Ringstad, and Ansgar Heck
- Subjects
General Medicine - Published
- 2023
- Full Text
- View/download PDF
8. Brain monitoring in hospitals needs to be strengthened
- Author
-
Anne Hege, Aamodt, Erik, Taubøll, Tom, Eichele, Luis, Romundstad, Angelika, Sorteberg, Sean, Wallace, Annette, Fromm, Marie Furuholmen, Raastad, Trond, Sand, Karolina, Skagen, Agnethe, Eltoft, Christina, Kefaloykos, Shirin K, Frisvold, Kristian Bernhard, Nilsen, Maria, Carlsson, Geir, Bråthen, Ida, Bakke, Morten Andreas, Horn, Markus, Wiedmann, Bjørn, Tennøe, Jon André, Totland, Ole Morten, Rønning, Martin, Kurz, and Anette, Storstein more...
- Subjects
Norway ,Brain ,Humans ,Hospitals - Abstract
Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.
- Published
- 2021
9. Application of the GastroDuo as an in Vitro Dissolution Tool To Simulate the Gastric Emptying of the Postprandial Stomach
- Author
-
Markus Wiedmann, Philipp Schick, Franziska Wegner, Elisabeth Schapperer, Maximilian Sager, Mirko Koziolek, and Werner Weitschies
- Subjects
Adult ,Male ,Adolescent ,Administration, Oral ,Biological Availability ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Bioequivalence ,030226 pharmacology & pharmacy ,Sildenafil Citrate ,Young Adult ,03 medical and health sciences ,Febuxostat ,0302 clinical medicine ,Pharmacokinetics ,Drug Discovery ,medicine ,Humans ,Dissolution testing ,Aged ,Peristalsis ,Gastric emptying ,Chemistry ,Stomach ,Middle Aged ,Postprandial Period ,021001 nanoscience & nanotechnology ,Drug Liberation ,Kinetics ,medicine.anatomical_structure ,Postprandial ,Gastric Emptying ,Solubility ,Molecular Medicine ,0210 nano-technology ,Digestion - Abstract
In the postprandial stomach, processes such as secretion, digestion, and gastric emptying all occur simultaneously. Therefore, the system is highly heterogeneous and dynamically changing, for instance, in terms of various physicochemical parameters such as pH value or viscosity. Thus, the administration of a drug together with food can result in highly variable drug plasma concentrations, which may affect the efficacy and safety of the pharmacotherapy. In this work, the pharmacokinetic (PK) data obtained from two fed-state bioequivalence studies with the immediate release (IR) drug products Viagra (sildenafil) and Adenuric (febuxostat) have been analyzed. This evaluation revealed that basically three characteristic types of onset behaviors of drug plasma concentration can be distinguished. It was hypothesized that the different types of onset behaviors were mainly caused by the interplay between gastric drug dissolution and gastric emptying. To study this interplay in vitro, a biopredictive dissolution tool-GastroDuo-was developed and used for both drug products. Therefore, three different test programs have been applied to simulate certain aspects of the postprandial human stomach, which included dynamic pH changes, gastric peristalsis, and the kinetics of gastric emptying. Specifically, the behavior of noncaloric fluids by the so-called "Magenstrasse" was taken into deeper consideration. The experiments revealed that the dissolution and emptying behavior of the two drug products were affected in different ways by the three test programs. The in vitro data nicely explained the tendencies of the drug products for certain types of onset behaviors observed in the PK data. While Viagra was strongly affected by simulated peristalsis, Adenuric was more sensitive to the simulated emptying kinetics. This work clearly demonstrated the important role of gastric fluid emptying for the onset of drug plasma concentration after oral administration of IR formulations in the fed state. Moreover, this was the first study in which GastroDuo was applied as a biopredictive in vitro model which is able to simulate crucial parameters of the human stomach (e.g., pH profiles and gastric emptying) in a realistic manner. more...
- Published
- 2019
- Full Text
- View/download PDF
10. Hjerneovervåking i sykehusene må styrkes
- Author
-
Maria Carlsson, Kristian Bernhard Nilsen, Shirin K. Frisvold, Anette Storstein, Agnethe Eltoft, Ole Morten Rønning, Trond Sand, Marie Furuholmen Raastad, Erik Taubøll, Bjørn Tennøe, Jon André Totland, Geir Bråthen, Martin W. Kurz, Christina Kefaloykos, Sean Wallace, Markus Wiedmann, Anne Hege Aamodt, Luis Romundstad, Karolina Skagen, Angelika Sorteberg, Annette Fromm, Tom Eichele, Ida Bakke, and Morten Andreas Horn more...
- Subjects
business.industry ,Medicine ,General Medicine ,Medical emergency ,Brain monitoring ,business ,medicine.disease - Abstract
Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.
- Published
- 2021
- Full Text
- View/download PDF
11. Thrombosis and thrombocytopenia after CHADOX1 NCoV-19 vaccination
- Author
-
Nina Haagenrud Schultz, Pål Andre Holme, Fridtjof Lund-Johansen, Maria T. Ahlen, Geir E. Tjønnfjord, Thor Håkon Skattør, Markus Wiedmann, Anne Hege Aamodt, Annika E. Michelsen, Ingvild H. Sørvoll, and Ludvig A. Munthe more...
- Subjects
education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,General Medicine ,Heparin ,030204 cardiovascular system & hematology ,medicine.disease ,Thrombosis ,Vaccination ,03 medical and health sciences ,Venous thrombosis ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Medicine ,Platelet ,030212 general & internal medicine ,education ,business ,Platelet factor 4 ,medicine.drug - Abstract
We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia. more...
- Published
- 2021
12. How I do it: endoscopic endonasal resection of tuberculum sellae meningioma
- Author
-
Jon Berg-Johnsen, Aslan Lashkarivand, Markus Wiedmann, and Daniel Dahlberg
- Subjects
medicine.medical_specialty ,Skull Base Neoplasms ,030218 nuclear medicine & medical imaging ,Resection ,Meningioma ,Tuberculum Sellae Meningioma ,03 medical and health sciences ,0302 clinical medicine ,Visual evoked potentials ,medicine ,Meningeal Neoplasms ,Humans ,Endoscopic endonasal approach ,Sella Turcica ,Neuroradiology ,medicine.diagnostic_test ,business.industry ,Microsurgical technique ,Interventional radiology ,medicine.disease ,Neurovascular bundle ,medicine.anatomical_structure ,Treatment Outcome ,Neuroendoscopy ,Tuberculum sellae ,Skull base surgery ,Surgery ,Neurology (clinical) ,Radiology ,Neurosurgery ,business ,How I Do it - Tumor - Meningioma ,030217 neurology & neurosurgery - Abstract
Background Tuberculum sellae meningiomas (TSMs) adherent to neurovascular structures are particularly challenging lesions requiring delicate and precise microneurosurgery. There is an ongoing debate about the optimal surgical approach. Method We describe technical nuances and challenges in TSM resection using the endoscopic endonasal approach (EEA) in two cases of fibrous tumors with adherence to neurovascular structures. The cases are illustrated with a video (case 1) and figures (cases 1 and 2). Conclusion A dedicated team approach and precise microsurgical technique facilitate safe resection of complex TSMs through the EEA. more...
- Published
- 2020
13. Treatment of ruptured aneurysms of the choroidal collateral system in moyamoya disease: a systematic review and data analysis
- Author
-
Chris Davidoff, Wei Ni, Anna Lo Presti, Mary Simons, Jong Kook Rhim, Markus Wiedmann, and Marcus A. Stoodley
- Subjects
Data Analysis ,medicine.medical_specialty ,Nausea ,business.industry ,medicine.medical_treatment ,MEDLINE ,Intracranial Aneurysm ,General Medicine ,Aneurysm, Ruptured ,Revascularization ,medicine.disease ,Surgery ,Aneurysm ,medicine.anatomical_structure ,Treatment Outcome ,medicine ,Vomiting ,Etiology ,Humans ,Moyamoya disease ,medicine.symptom ,Moyamoya Disease ,business ,Carotid Artery, Internal ,Artery - Abstract
OBJECTIVE Moyamoya disease (MMD) is a chronic, progressive steno-occlusive condition of the distal internal carotid arteries of unknown etiology. Collateral arterial networks typically develop in MMD, bypassing the steno-occlusion. Aneurysms arising on the collateral networks are a known source of hemorrhage. The choroidal collateral system is the most common location for collateral pathway aneurysms in MMD and associated hemorrhage. The authors performed data collection and analysis to further elucidate the best treatment approaches for ruptured aneurysms of the choroidal collateral system in MMD, which as yet remain unclear. METHODS A comprehensive data collection and analysis of case reports and case series with ruptured choroidal collateral artery aneurysms (CCAAs) was performed. PRISMA guidelines for systematic reviews were followed and the Medline, Embase, and Scopus databases were searched for relevant studies. A database was created including patients with ruptured CCAA in MMD. Original data from case series were included whenever possible. A previously unreported case of a ruptured choroidal artery aneurysm in MMD treated by the authors was also included. RESULTS The database comprised 72 patients with ruptured CCAA in MMD. The most common clinical symptoms were headache, nausea, and vomiting (39%). Initially, a conservative treatment approach was chosen in 29% of cases but led to rehemorrhage in 40% of cases; 63% of these rehemorrhages occurred during the first 35 days. Endovascular treatment seemed a safe option for aneurysm exclusion, mainly through parent vessel sacrifice, but had a treatment failure rate of 21%, due to inadequate access. Aneurysm treatment with revascularization as the initial treatment strategy led to aneurysm regression in 82% with no reported rehemorrhage. Aneurysm exclusion through open surgery was effective but was associated with a relatively high complication rate (25%). Outcome after rupture of CCAA was poor, with 41% of patients deceased or permanently disabled. Overall, patient outcomes were better in the endovascular and revascularization treatment group than in the conservative treatment group. CONCLUSIONS Rupture of CCAA in MMD is associated with high morbidity and rerupture rate requiring urgent treatment. more...
- Published
- 2020
14. Deliberate employment of postoperative hypotension for brain arteriovenous malformation surgery and the incidence of delayed postoperative hemorrhage: a prospective cohort study
- Author
-
Gillian Z. Heller, Nazih Assaad, Michael Parr, Michael K. Morgan, and Markus Wiedmann
- Subjects
Adult ,Intracranial Arteriovenous Malformations ,Male ,Microsurgery ,medicine.medical_specialty ,animal structures ,Postoperative Hemorrhage ,Neurosurgical Procedures ,030218 nuclear medicine & medical imaging ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Modified Rankin Scale ,law ,Intensive care ,medicine ,Humans ,Cerebral perfusion pressure ,Prospective cohort study ,Postoperative Care ,business.industry ,Incidence ,fungi ,General Medicine ,Odds ratio ,Middle Aged ,Intensive care unit ,Surgery ,Treatment Outcome ,Blood pressure ,Anesthesia ,Female ,Hypotension ,business ,030217 neurology & neurosurgery ,Postoperative Hypertension - Abstract
OBJECTIVEThe aim of this study was to examine the impact of deliberate employment of postoperative hypotension on delayed postoperative hemorrhage (DPH) for all Spetzler-Ponce Class (SPC) C brain arteriovenous malformations (bAVMs) and SPC B bAVMs ≥ 3.5 cm in diameter (SPC B 3.5+).METHODSA protocol of deliberate employment of postoperative hypotension was introduced in June 1997 for all SPC C and SPC B 3.5+ bAVMs. The aim was to achieve a maximum mean arterial blood pressure (BP) ≤ 70 mm Hg (with cerebral perfusion pressure > 50 mm Hg) for a minimum of 7 days after resection of bAVMs (BP protocol). The authors compared patients who experienced DPH (defined as brain hemorrhage into the resection bed that resulted in a new neurological deficit or that resulted in reoperation during the hospitalization for microsurgical bAVM resection) between 2 periods (prior to adopting the BP protocol and after introduction of the BP protocol) and 4 bAVM categories (SPC A, SPC B 3.5− [that is, SPC B < 3.5 cm maximum diameter], SPC B 3.5+, and SPC C). Patients excluded from treatment by the BP protocol were managed in the intensive care unit to avoid moderate hypertensive episodes. The pooled cases of all bAVM treated by surgery were analyzed to identify characteristics associated with the risk of DPH. These identified characteristics were then examined by multiple logistic regression analysis in both SPC B 3.5+ and SPC C cases.RESULTSFrom a cohort of 641 bAVMs treated by microsurgery, 32 patients with DPH were identified. Of those, 66% (95% CI 48–80) had a permanent new neurological deficit with a modified Rankin Scale score of 2–6. This included a mortality rate of 13% (95% CI 4.4–29). The BP protocol was used to treat 162 patients with either SPC B 3.5+ or SPC C. For SPC B 3.5+, there was no significant reduction in DPH with the introduction of the BP protocol (p = 0.77). For SPC C, there was a significant (p = 0.035) reduction of DPH from 29% (95% CI 13%–53%) to 8.2% (95% CI 3.2%–18%) associated with the introduction of the BP protocol. Multiple logistic regression analysis found that the absence of the BP protocol (p = 0.011, odds ratio 7.5, 95% CI 1.6–36) remained significant for the development of DPH in patients with SPC C bAVMs.CONCLUSIONSTreating patients with SPC C bAVMs with a protocol that lowers BP immediately after resection seems to reduce the risk of DPH. For SPC A and SPC B 3.5− bAVMs, there is unlikely to be a need to do more than avoid postoperative hypertension. For SPC B 3.5+ bAVMs, a larger number of patients would be required to test the absence of benefit of the BP protocol. more...
- Published
- 2017
- Full Text
- View/download PDF
15. Radiation-Stimulated Translocation of CD166 and CRYAB to the Endothelial Surface Provides Potential Vascular Targets on Irradiated Brain Arteriovenous Malformations
- Author
-
Sinduja Subramanian, Mark P. Molloy, Zhenjun Zhao, Marcus A. Stoodley, Vivienne S. Lee, Lucinda S. McRobb, Markus Wiedmann, Andrew J. Gauden, Santhosh George Thomas, Matthew J. McKay, Vaughan Moutrie, and Michael Grace more...
- Subjects
Cell ,Cell junction ,vascular targeting ,lcsh:Chemistry ,Rats, Sprague-Dawley ,Mice ,0302 clinical medicine ,lcsh:QH301-705.5 ,Spectroscopy ,Cells, Cultured ,0303 health sciences ,Chemistry ,Activated-Leukocyte Cell Adhesion Molecule ,General Medicine ,3. Good health ,Computer Science Applications ,Cell biology ,Protein Transport ,medicine.anatomical_structure ,Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ,ionizing radiation ,Microtubule-Associated Proteins ,Intracellular ,Intracranial Arteriovenous Malformations ,stereotactic radiosurgery ,Radiosurgery ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,proteomics ,In vivo ,Heat shock protein ,medicine ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,030304 developmental biology ,brain arteriovenous malformation ,Organic Chemistry ,Cell Membrane ,Endothelial Cells ,Crystallins ,Rats ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gamma Rays ,030217 neurology & neurosurgery ,Immunostaining ,Ex vivo - Abstract
Vascular targeting with pro-thrombotic antibody-conjugates is a promising biological treatment for brain arteriovenous malformations (bAVMs). However, targeted drug delivery relies on the identification of unique or overexpressed markers on the surface of a target cell. In the absence of inherent biological markers, stereotactic radiosurgery may be used to prime induction of site-specific and targetable molecular changes on the endothelial surface. To investigate lumen-accessible, endothelial targets induced by radiation, we combined Gamma knife surgery in an AVM animal model with in vivo biotin-labeling and comparative proteomics. Two proteins, &alpha, B-crystallin (CRYAB)&mdash, a small heat shock protein that normally acts as an intracellular chaperone to misfolded proteins&mdash, and activated leukocyte cell adhesion molecule CD166, were further validated for endothelial surface expression after irradiation. Immunostaining of endothelial cells in vitro and rat AVM tissue ex vivo confirmed de novo induction of CRYAB following irradiation (20 Gy). Western analysis demonstrated that CRYAB accumulated intracellularly as a 20 kDa monomer, but, at the cell surface, a novel 65 kDa protein was observed, suggesting radiation stimulates translocation of an atypical CRYAB isoform. In contrast, CD166 had relatively high expression in non-irradiated cells, localized predominantly to the lateral surfaces. Radiation increased CD166 surface exposure by inducing translocation from intercellular junctions to the apical surface without significantly altering total protein levels. These findings reinforce the dynamic molecular changes induced by radiation exposure, particularly at the cell surface, and support further investigation of radiation as a priming mechanism and these molecules as putative targets for focused drug delivery in irradiated tissue. more...
- Published
- 2019
16. Complication-Effectiveness Analysis for Brain Arteriovenous Malformation Surgery
- Author
-
Michael K. Morgan, Markus Wiedmann, Nazih Assaad, and Gillian Z. Heller
- Subjects
Adult ,Intracranial Arteriovenous Malformations ,Male ,Microsurgery ,medicine.medical_specialty ,Databases, Factual ,medicine.medical_treatment ,Context (language use) ,Kaplan-Meier Estimate ,Risk Assessment ,Cohort Studies ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Recurrence ,Modified Rankin Scale ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,business.industry ,Brain ,Arteriovenous malformation ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Neurology (clinical) ,Tomography, X-Ray Computed ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background Intervention for brain arteriovenous malformations (bAVMs) should aim at treatment that is safe and effective. Objective To analyze a prospective database to derive the probability of neurological deficit and adjust this risk for effectively treated bAVMs (complication-effectiveness analysis [CEA]). Methods First, we calculated the percentage of surgical complications leading to a modified Rankin Scale >1 at 12 months after surgery for each Spetzler-Ponce class (SPC). Second, we performed a sensitivity analysis of these results by including bAVMs not undergoing surgery, to correct for bias. Third, we established the long-term cumulative incidence of freedom from recurrence from Kaplan-Meier analysis. Finally, we combined the results to calculate the risk of surgery per effective treatment in a complication-effectiveness analysis. Results Seven hundred seventy-nine patients underwent 641 microsurgical resections. Complications of surgery leading to a modified Rankin Scale >1 at 12 months occurred in 1.4% (95% confidence interval [CI]: 0.5-3.3), 20% (95% CI: 15-26), and 41% (95% CI: 30-52) of SPC A, SPC B, and SPC C, respectively. The cumulative 9-year freedom from recurrence was 97% for SPC A and 92% for other bAVMs. The 9-year CEA risk was 1.4% (credible range: 0.5%-3.4%) for SPC A, 22% to 24% (credible range: 16%-31%) for SPC B, and 45% to 63% (credible range: 33%-73%) for SPC C bAVM. Conclusion CEA presents the treatment outcome in the context of efficacy and provides a basis for comparing outcomes from techniques with different times to elimination of the bAVM. Abbreviations bAVM, brain arteriovenous malformationCEA, complication-effectiveness analysisCI, confidence intervalCTA, computerized tomographic angiographyDSA, digital subtraction angiographyMRA, magnetic resonance angiographymRS, modified Rankin ScaleSMG, Spetzler-Martin gradeSPC, Spetzler-Ponce class. more...
- Published
- 2016
- Full Text
- View/download PDF
17. Complication-Effectiveness Analysis for Unruptured Intracranial Aneurysm Surgery
- Author
-
Markus Wiedmann, Michael K. Morgan, Gillian Z. Heller, and Nazih Assaad
- Subjects
Male ,Reoperation ,medicine.medical_specialty ,Databases, Factual ,Kaplan-Meier Estimate ,Aneurysm, Ruptured ,Logistic regression ,Risk Assessment ,Neurosurgical Procedures ,030218 nuclear medicine & medical imaging ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Modified Rankin Scale ,Humans ,Medicine ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Aged ,Posterior Cerebral Artery ,business.industry ,Intracranial Aneurysm ,Odds ratio ,Middle Aged ,Confidence interval ,Surgery ,Treatment Outcome ,Cerebrovascular Circulation ,Female ,Neurology (clinical) ,Risk assessment ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background The aim of intervention for unruptured intracranial aneurysms (UIAs) is safe, effective treatment. Objective To analyze a prospective database for variables influencing the risk of surgery to produce a risk model adjusting this risk for effectively treated aneurysms. Methods First, we identified variables to create a model from multiple logistic regression for complications of surgery leading to a 12-month modified Rankin Scale score >1. Second, we established the long-term cumulative incidence of freedom from retreatment or rupture (treated aneurysm) from Kaplan-Meier analysis. Third, we combined these analyses to establish a model of risk of surgery per effective treatment. Results One thousand twelve patients with 1440 UIA underwent 1080 craniotomies. We found that 10.1% (95% confidence interval [CI], 8.4-12.0) of craniotomies resulted in a complication leading to a modified Rankin Scale score >1 at 12 months. Logistic regression found age (odds ratio, 1.04; 95% CI, 1.02-1.06), size (odds ratio, 1.12; 95% CI, 1.09-1.15), and posterior circulation location (odds ratio, 2.95; 95% CI, 1.82-4.78) to be significant. Cumulative 10-year risk of retreatment or rupture was 3.0% (95% CI, 1.3-7.0). The complication-effectiveness model was derived by dividing the complication risk by the 10-year cumulative freedom from retreatment or rupture proportion. Risk per effective treatment ranged from 1% for a 5-mm anterior circulation UIA in a 20-year-old patient to 70% for a giant posterior circulation UIA in a 70-year-old patient. Conclusion Complication-effectiveness analyses increase the information available with regard to outcome for the management of UIAs. more...
- Published
- 2016
- Full Text
- View/download PDF
18. Foster Kennedys syndrom
- Author
-
Øystein Kalsnes Jørstad, Markus Wiedmann, Donata Biernat, Daniel Dahlberg, and Jon Roger Eidet
- Subjects
General Medicine - Published
- 2019
- Full Text
- View/download PDF
19. Smoking, obesity and the risk of pituitary adenoma: a large prospective cohort study (The HUNT Study)
- Author
-
Cathrine Brunborg, John-Anker Zwart, Kristina Lindemann, Eirik Helseth, Tom Børge Johannesen, Lars J. Vatten, and Markus Wiedmann
- Subjects
Adenoma ,Adult ,Male ,Risk ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Epidemiology ,Overweight ,Body Mass Index ,03 medical and health sciences ,Age Distribution ,0302 clinical medicine ,medicine ,Humans ,Pituitary Neoplasms ,Obesity ,Prospective Studies ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Norway ,business.industry ,Smoking ,Retrospective cohort study ,Middle Aged ,medicine.disease ,030104 developmental biology ,Population Surveillance ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Risk assessment ,business ,Body mass index ,Follow-Up Studies ,Cohort study - Published
- 2015
- Full Text
- View/download PDF
20. Effect of Coadministered Water on the In Vivo Performance of Oral Formulations Containing N-Acetylcysteine: An In Vitro Approach Using the Dynamic Open Flow-Through Test Apparatus
- Author
-
Werner Weitschies, Felix Schneider, Ellen Schremmer, Philipp Jedamzik, Maximilian Sager, Mirko Koziolek, and Markus Wiedmann
- Subjects
Drug ,Adult ,Male ,media_common.quotation_subject ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Administration, Oral ,02 engineering and technology ,Pharmacology ,In Vitro Techniques ,030226 pharmacology & pharmacy ,Dosage form ,Biopharmaceutics ,Acetylcysteine ,03 medical and health sciences ,Food-Drug Interactions ,Young Adult ,0302 clinical medicine ,Drug Delivery Systems ,Oral administration ,In vivo ,Drug Discovery ,medicine ,Humans ,Dissolution testing ,media_common ,Cross-Over Studies ,Gastric emptying ,Chemistry ,Water ,Middle Aged ,021001 nanoscience & nanotechnology ,In vitro ,Healthy Volunteers ,Absorption, Physiological ,Drug Liberation ,Gastric Emptying ,Solubility ,Molecular Medicine ,Female ,0210 nano-technology ,medicine.drug ,Tablets - Abstract
The drug plasma profile after oral administration of immediate release dosage forms can be affected by the human gastrointestinal physiology, the formulation, and the drug itself. In this work, we investigated the in vivo and in vitro performance of two formulations (granules vs. tablet) containing the highly soluble drug N-Acetylcysteine (BCS class I). Thereby, special attention was paid to the effect of the dosage form and the coadministration of water on drug release. Interestingly, the in vivo results from a pharmacokinetic study with 11 healthy volunteers indicated that the drug plasma concentrations were comparable for the tablet given with water as well as for the granules given with and without water. In order to mechanistically understand this outcome, we used a biorelevant dissolution test device, the dynamic open flow-through test apparatus. With the aid of this test apparatus, we were able to simulate biorelevant parameters, such as gastric emptying, hydrodynamic flow as well as physical stress. By this, it was possible to mimic the intake conditions of the clinical trial (i.e., drug intake with and without water). Whereas the experiments in the USP paddle apparatus revealed differences between the two formulations, we could not observe significant differences in the release profiles of the two formulations by using the dynamic open flow-through test apparatus. Even by considering the different intake conditions, drug release was slow and amounted to around 30% until simulated gastric emptying. These results suggest that dissolution was irrespective of coadministered water and the formulation. Despite the high aqueous solubility of N-Acetylcysteine, the limiting factor for drug release was the slow dissolution rate in relation to the gastric emptying rate under simulated gastric conditions. Thus, in case of administration together with water, large amounts of the drug are still present in the stomach even after complete gastric emptying of the water. Consequently, the absorption of the drug is largely controlled by the nature of gastric emptying of the remaining drug. The data of this study indicated that the water emptying kinetics are only determining drug absorption if drug release is rapid enough. If this is not the case, physiological mechanisms, such as the migrating motor complex, play an important role for oral drug delivery. more...
- Published
- 2017
21. Overweight, obesity and height as risk factors for meningioma, glioma, pituitary adenoma and nerve sheath tumor: a large population-based prospective cohort study
- Author
-
Kristina Lindemann, J.A. Zwart, Eirik Helseth, Antonio Di Ieva, Lars J. Vatten, Markus Wiedmann, Tom Børge Johannesen, and Cathrine Brunborg
- Subjects
Oncology ,Adenoma ,medicine.medical_specialty ,Overweight ,Nerve Sheath Neoplasms ,Meningioma ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Glioma ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Pituitary Neoplasms ,Obesity ,Prospective Studies ,Prospective cohort study ,business.industry ,Cancer ,Hematology ,General Medicine ,medicine.disease ,Body Height ,Cancer registry ,Surgery ,Nerve sheath tumor ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background: In 2016, the International Agency for Research on Cancer (IARC) has announced that avoiding body fatness (i.e. overweight and obesity) contributes to prevent meningioma occurrence, but considered the available evidence for glioma inadequate. The association of body fatness with other CNS tumor subgroups is largely unknown. Objectives: To assess whether body fatness or body height are associated with risk for meningioma, glioma, pituitary adenoma (PA) or nerve sheath tumor (NST) in a large population-based Norwegian cohort. Methods: In this prospective cohort study of 1.8 million Norwegian residents, weight and height were measured at baseline and incident intracranial tumors were subsequently identified by linkage to the Cancer Registry of Norway. Cox regression analyses were performed to estimate risk for each tumor subgroup in relation to anthropometric measures, stratified by sex and in different age groups. Results: During 54 million person-years of follow-up 3335 meningiomas, 4382 gliomas, 1071 PAs and 759 NSTs were diagnosed. Obesity (BMI ≥30 kg/m2) was not associated with risk for meningioma or glioma, but was significantly associated with risk for PA (HR 1.43; 95% CI 1.09–1.88) compared with the reference group (BMI 20–24.9 kg/m2). For intracranial NSTs, obesity was associated with reduced tumor risk (HR 0.68; 95% CI 0.46–0.99). Body height was associated with increased risk for all four tumor subgroups. Conclusions: This study does not confirm overweight or obesity as risk factors for meningioma. Additionally, overweight and obesity can be quite confidently excluded as risk factors for glioma. However, this study indicates that body fatness increases the risk for PA, while it reduces the risk for NST. more...
- Published
- 2017
22. Body mass index and the risk of meningioma, glioma and schwannoma in a large prospective cohort study (The HUNT Study)
- Author
-
Lars J. Vatten, Markus Wiedmann, Kristina Lindemann, Cathrine Brunborg, John-Anker Zwart, Eirik Helseth, and Tom Børge Johannesen
- Subjects
Central Nervous System ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,genetic structures ,Epidemiology ,body mass index ,Schwannoma ,meningioma ,Cohort Studies ,Meningioma ,Sex Factors ,Risk Factors ,Sex factors ,Glioma ,Hunt study ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Obesity ,Prospective Studies ,Prospective cohort study ,schwannoma ,neoplasms ,business.industry ,medicine.disease ,Body Height ,nervous system diseases ,Surgery ,Female ,business ,Body mass index ,Neurilemmoma ,CNS tumour risk ,Cohort study - Abstract
Background: Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS). Methods: In a large population study (The Nord–Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma. Results: A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0–25) of follow-up. In obese women (BMI ⩾30 kg m−2), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97–2.92, P-trend=0.05) than in the reference group (BMI 20–24.9 kg m−2), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ⩾25 kg m−2) with the risk of schwannoma (HR=0.48, 95% CI: 0.23–0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup. Conclusion: These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk. more...
- Published
- 2013
- Full Text
- View/download PDF
23. Microsurgery for Spetzler-Ponce Class A and B arteriovenous malformations utilizing an outcome score adopted from Gamma Knife radiosurgery: a prospective cohort study
- Author
-
Markus Wiedmann, Marcus A. Stoodley, Michael K. Morgan, and Gillian Z. Heller
- Subjects
Intracranial Arteriovenous Malformations ,medicine.medical_specialty ,Microsurgery ,medicine.medical_treatment ,Radiosurgery ,03 medical and health sciences ,0302 clinical medicine ,Modified Rankin Scale ,medicine ,Humans ,030212 general & internal medicine ,Embolization ,Prospective Studies ,Prospective cohort study ,business.industry ,Arteriovenous malformation ,General Medicine ,medicine.disease ,Surgery ,Treatment Outcome ,Cohort ,Radiology ,Complication ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
OBJECTIVEThe purpose of this study was to adapt and apply the extended definition of favorable outcome established for Gamma Knife radiosurgery (GKRS) to surgery for brain arteriovenous malformations (bAVMs). The aim was to derive both an error around the point estimate and a model incorporating angioarchitectural features in order to facilitate comparison among different treatments.METHODSA prospective microsurgical cohort was analyzed. This cohort included patients undergoing embolization who did not proceed to microsurgery and patients denied surgery because of perceived risk of treatment. Data on bAVM residual and recurrence during long-term follow-up as well as complications of surgery and preoperative embolization were analyzed. Patients with Spetzler-Ponce Class C bAVMs were excluded because of extreme selection bias. First, patients with a favorable outcome were identified for both Class A and Class B lesions. Patients were considered to have a favorable outcome if they were free of bAVM recurrence or residual at last follow-up, with no complication of surgery or preoperative embolization, and a modified Rankin Scale score of more than 1 at 12 months after treatment. Patients who were denied surgery because of perceived risk, but would otherwise have been candidates for surgery, were included as not having a favorable outcome. Second, the authors analyzed favorable outcome from microsurgery by means of regression analysis, using as predictors characteristics previously identified to be associated with complications. Third, they created a prediction model of favorable outcome for microsurgery dependent upon angioarchitectural variables derived from the regression analysis.RESULTSFrom a cohort of 675 patients who were either treated or denied surgery because of perceived risk of surgery, 562 had Spetzler-Ponce Class A or B bAVMs and were included in the analysis. Logistic regression for favorable outcome found decreasing maximum diameter (continuous, OR 0.62, 95% CI 0.51–0.76), the absence of eloquent location (OR 0.23, 95% CI 0.12–0.43), and the absence of deep venous drainage (OR 0.19, 95% CI 0.10–0.36) to be significant predictors of favorable outcome. These variables are in agreement with previous analyses of microsurgery leading to complications, and the findings support the use of favorable outcome for microsurgery. The model developed for angioarchitectural features predicts a range of favorable outcome at 8 years following microsurgery for Class A bAVMs to be 88%–99%. The same model for Class B bAVMs predicts a range of favorable outcome of 62%–90%.CONCLUSIONSFavorable outcome, derived from GKRS, can be successfully used for microsurgical cohort series to assist in treatment recommendations. A favorable outcome can be achieved by microsurgery in at least 90% of cases at 8 years following microsurgery for patients with bAVMs smaller than 2.5 cm in maximum diameter and, in the absence of either deep venous drainage or eloquent location, patients with Spetzler-Ponce Class A bAVMs of all diameters. For patients with Class B bAVMs, this rate of favorable outcome can only be approached for lesions with a maximum diameter just above 6 cm or smaller and without deep venous drainage or eloquent location. more...
- Published
- 2016
24. Abstract WMP120: Radiosurgery Induces Novel Protein Changes on the Endothelium of Arteriovenous Malformations: Potential for Therapeutic Targets
- Author
-
Lucinda S McRobb, Vivienne S Lee, Santosh G Thomas, Markus Wiedmann, Jude V Amal Raj, Zhenjun Zhao, Michael Grace, Vaughan Moutrie, Matthew McKay, Mark Molloy, and Marcus A Stoodley
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Brain arteriovenous malformations (AVMs) are a significant cause of hemorrhagic stroke. Almost one third are untreatable using current methods. We aim to use stereotactic radiosurgery as a priming tool to elicit novel protein expression on irradiated AVM vessels and targeting with thrombotic antibody-conjugates to induce rapid thrombosis and vessel closure. Hypothesis: Radiosurgery induces novel protein changes on the AVM endothelium that are potential therapeutic targets. Methods: A model arteriovenous fistula (AVF) formed in rats was irradiated by GammaKnife (20Gy) or sham-irradiated. After 24h, animals were perfused with EZ-link Sulfo-NHS-LC Biotin to label surface-accessible proteins. Biotinylated AVFs were dissected, pooled (n=4/group) and protein extracted. Biotin-labelled proteins were enriched on streptavidin-agarose beads before LC-MS/MS using SWATH acquisition label-free mass spectrometry. Results: At 24h post-irradiation, 280 surface-associated proteins were identified in sham and irradiated extracts. Of these, 56 were up-regulated in irradiated AVMs (greater than 1.5-fold change vs sham). Radiation increased fibrinogen α/β (1.5-fold), platelet factor 4 (16-fold) and plasminogen (2-fold), suggesting enhanced adhesion of blood-borne molecules to the vessel wall. Twenty-eight mitochondrial proteins increased, including manganese superoxide dismutase (2-fold), which may reflect radiation-induced changes in subcellular localization or cell lysis causing intracellular molecule release and entrapment. Troponin I (cardiac) and tropomyosin 1α, actin-associated proteins externalized under stress, increased 14- and 4-fold. Secreted and membrane proteins were also identified (e.g. clusterin, 1.5-fold; CD93, 5-fold; Ras-related Rab18, 1.8-fold). Conclusions: Using in vivo biotin labelling, we have identified a series of novel surface-accessible proteins induced by radiosurgery that are potential therapeutic targets. Externalization of intracellular proteins may provide unique radiation-stimulated candidates for vascular targeting in AVMs. more...
- Published
- 2016
- Full Text
- View/download PDF
25. Factors Associated With Proximal Intracranial Aneurysms to Brain Arteriovenous Malformations: A Prospective Cohort Study
- Author
-
Khalid Alsahli, Gillian Z. Heller, Markus Wiedmann, Michael K. Morgan, and Nazih Assaad
- Subjects
Adult ,Intracranial Arteriovenous Malformations ,Male ,medicine.medical_specialty ,Adolescent ,Hemodynamics ,Logistic regression ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Aneurysm ,Internal medicine ,medicine ,Odds Ratio ,Humans ,Prospective Studies ,Prospective cohort study ,business.industry ,Arteriovenous malformation ,Intracranial Aneurysm ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Logistic Models ,Cohort ,Multivariate Analysis ,Cardiology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background The risk of hemorrhage from a brain arteriovenous malformation (bAVM) is increased when an associated proximal intracranial aneurysm (APIA) is present. Identifying factors that are associated with APIA may influence the prediction of hemorrhage in patients with bAVM. Objective To identify patient- and bAVM-specific factors associated with APIA. Methods We analyzed a prospective database of bAVMs for factors associated with the presence of APIA. Factors analyzed included age, sex, bAVM size, aneurysm size, circulation contributing to the bAVM, location of the aneurysm, deep venous drainage, and Spetzler-Ponce categories. Multiple logistic regression was performed to identify an association with APIA. Results Of 753 cases of bAVM with complete angiographic surveillance, 67 (9%) were found to have APIA. Older age (continuous variable; odds ratio, 1.04; 95% confidence interval, 1.02-1.05) and posterior circulation supply to the bAVM (odds ratio, 2.29; 95% confidence interval, 1.32-3.99) were factors associated with increased detection of APIA. The association of posterior circulation-supplied bAVM was not due to infratentorial bAVM location because 72% of posterior circulation APIAs were supplying supratentorial bAVM. Conclusion APIAs appear to develop with time, as evident from the increased age for those with APIAs. Furthermore, they were more likely present in bAVMs supplied by the posterior circulation. This may be due to a difference in hemodynamic stress. Abbreviations APIA, associated proximal intracranial aneurysmbAVM, brain arteriovenous malformationDSA, digital subtraction angiographySMG, Spetzler-Martin gradeSPC, Spetzler-Ponce category. more...
- Published
- 2015
26. Radiosurgery Alters the Endothelial Surface Proteome: Externalized Intracellular Molecules as Potential Vascular Targets in Irradiated Brain Arteriovenous Malformations
- Author
-
Vivienne S. Lee, Margaret Simonian, Zhenjun Zhao, Marcus A. Stoodley, Markus Wiedmann, Jude V. Amal Raj, Matthew J. McKay, Vaughan Moutrie, Lucinda S. McRobb, Michael Grace, Santhosh George Thomas, and Mark P. Molloy more...
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Proteome ,Endothelium ,Protein subunit ,Intracellular Space ,Biophysics ,Inflammation ,Biology ,Radiosurgery ,Proteomics ,Cell Line ,Arteriovenous Malformations ,Rats, Sprague-Dawley ,03 medical and health sciences ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Radiation ,Brain ,Endothelial Cells ,Rats ,Transport protein ,Protein Transport ,030104 developmental biology ,medicine.anatomical_structure ,medicine.symptom ,Immunostaining ,Blood vessel - Abstract
Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs) that drives blood vessel closure through cellular proliferation, thrombosis and fibrosis, but is limited by a delay to occlusion of 2-3 years and a maximum treatable size of 3 cm. In this current study we used SRS as a priming tool to elicit novel protein expression on the endothelium of irradiated AVM vessels, and these proteins were then targeted with prothrombotic conjugates to induce rapid thrombosis and vessel closure. SRS-induced protein changes on the endothelium in an animal model of AVM were examined using in vivo biotin labeling of surface-accessible proteins and comparative proteomics. LC-MS/MS using SWATH acquisition label-free mass spectrometry identified 280 proteins in biotin-enriched fractions. The abundance of 56 proteins increased after irradiation of the rat arteriovenous fistula (20 Gy, ≥1.5-fold). A large proportion of intracellular proteins were present in this subset: 29 mitochondrial and 9 cytoskeletal. Three of these proteins were chosen for further validation based on previously published evidence for surface localization and a role in autoimmune stimulation: cardiac troponin I (TNNI3); manganese superoxide dismutase (SOD2); and the E2 subunit of the pyruvate dehydrogenase complex (PDCE2). Immunostaining of AVM vessels confirmed an increase in abundance of PDCE2 across the vessel wall, but not a measurable increase in TNNI3 or SOD2. All three proteins co-localized with the endothelium after irradiation, however, more detailed subcellular distribution could not be accurately established. In vitro, radiation-stimulated surface translocation of all three proteins was confirmed in nonpermeabilized brain endothelial cells using immunocytochemistry. Total protein abundance increased modestly after irradiation for PDCE2 and SOD2 but decreased for TNNI3, suggesting that radiation primarily affects subcellular distribution rather than protein levels. The novel identification of these proteins as surface exposed in response to radiation raises important questions about their potential role in radiation-induced inflammation, fibrosis and autoimmunity, but may also provide unique candidates for vascular targeting in brain AVMs and other vascular tissues. more...
- Published
- 2017
- Full Text
- View/download PDF
27. The impact of body mass index and height on the risk for glioblastoma and other glioma subgroups: a large prospective cohort study
- Author
-
Antonio Di Ieva, Kristina Lindemann, Cathrine Brunborg, J.A. Zwart, Eirik Helseth, Tom Børge Johannesen, Lars J. Vatten, and Markus Wiedmann
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Oligoastrocytoma ,Clinical Investigations ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Glioma ,medicine ,Prospective cohort study ,neoplasms ,business.industry ,Hazard ratio ,Not Otherwise Specified ,medicine.disease ,nervous system diseases ,030220 oncology & carcinogenesis ,Neurology (clinical) ,Oligodendroglioma ,business ,Body mass index ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background Glioma comprises a heterogeneous group of mostly malignant brain tumors, whereof glioblastoma (GBM) represents the largest and most lethal subgroup. Body height and body mass index (BMI) are risk factors for other cancers, but no previous study has examined anthropometric data in relation to different glioma subgroups. Methods This prospective cohort study includes 1.8 million Norwegian women and men between ages 14 and 80 years at baseline. Body weight and height were measured, and incident cases of glioma were identified by linkage to the National Cancer Registry. Cox regression analyses were performed to evaluate risk for different glioma subgroups in relation to anthropometric measures. Results During 54 million person-years of follow-up, 4,382 gliomas were identified. Overweight and obesity were not associated with risk for any glioma subgroup. Height was positively associated with risk for GBM and all other gliomas (hazard ratio [HR] per 10 cm increase: 1.24; 95% confidence interval [CI], 1.17-1.31 and 1.18; 95% CI, 1.09-1.29) but not with the proxy for isocitrate dehydrogenase (IDH)-mutant glioma (HR, 1.09; 95% CI, 0.98-1.21). In further subgroup analyses, the effect of height on glioma risk varied significantly with positive associations for oligoastrocytoma (HR, 1.74; 95% CI, 1.20-2.53) and malignant glioma not otherwise specified (NOS) (HR, 1.42; 95% CI, 1.16-1.76, but not with diffuse astrocytoma (WHO grades II and III) or oligodendroglioma. Conclusion This epidemiologic study consolidates height as a risk factor for GBM and other gliomas. It further indicates that this association is not universal for gliomas but may differ between different glioma subgroups. more...
- Published
- 2016
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.