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3. Routine ICU admission after brain tumor surgery: retrospective validation and critical appraisal of two prediction scores

Author

Jan-Oliver Neumann, Stephanie Schmidt, Amin Nohman, Martin Jakobs, and Andreas Unterberg

Subjects
Surgery, Neurology (clinical)
Abstract

Background Routine admission to an intensive care unit (ICU) following brain tumor surgery has been a common practice for many years. Although this practice has been challenged by many authors, it has still not changed widely, mainly due to the lack of reliable data for preoperative risk assessment. Motivated by this dilemma, risk prediction scores for postoperative complications following brain tumor surgery have been developed recently. In order to improve the ICU admission policy at our institution, we assessed the applicability, performance, and safety of the two most appropriate risk prediction scores. Methods One thousand consecutive adult patients undergoing elective brain tumor resection within 19 months were included. Patients with craniotomy for other causes, i.e., cerebral aneurysms and microvascular decompression, were excluded. The decision for postoperative ICU-surveillance was made by joint judgment of the operating surgeon and the anesthesiologist. All data and features relevant to the scores were extracted from clinical records and subsequent ICU or neurosurgical floor documentation was inspected for any postoperative adverse events requiring ICU admission. The CranioScore derived by Cinotti et al. (Anesthesiology 129(6):1111–20, 5) and the risk assessment score of Munari et al. (Acta Neurochir (Wien) 164(3):635–641, 15) were calculated and prognostic performance was evaluated by ROC analysis. Results In our cohort, both scores showed only a weak prognostic performance: the CranioScore reached a ROC-AUC of 0.65, while Munari et al.’s score achieved a ROC-AUC of 0.67. When applying the recommended decision thresholds for ICU admission, 64% resp. 68% of patients would be classified as in need of ICU surveillance, and the negative predictive value (NPV) would be 91% for both scores. Lowering the thresholds in order to increase patient safety, i.e., 95% NPV, would lead to ICU admission rates of over 85%. Conclusion Performance of both scores was limited in our cohort. In practice, neither would achieve a significant reduction in ICU admission rates, whereas the number of patients suffering complications at the neurosurgical ward would increase. In future, better risk assessment measures are needed.

Published
2023
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4. Perioperative morbidity and mortality in octogenarians sustaining traumatic osteoporotic type 4 and 5 thoracolumbar and lumbar fractures: a retrospective study with 3 years follow-up

Author

Pavlina Lenga, Gelo Gülec, Karl Kiening, Andreas W. Unterberg, and Basem Ishak

Subjects
Surgery, Neurology (clinical)
Abstract

Purpose This study aimed to guide the more efficient management of type 4 and 5 thoracolumbar or lumbar osteoporotic fractures (OF) in patients aged 80 years and older with an acute onset of neurological decline. This aim was achieved by assessing the clinical course and morbidity and mortality rates and identifying potential risk factors for patient mortality Methods Electronic medical records were retrieved from a single institution pertaining to the period between September 2005 and December 2020. Data on patient demographics, neurological conditions, surgical characteristics, complications, hospital course, and 90-day mortality were also collected. Results Over a 16-year period, 35 patients aged ≥80 years diagnosed with thoracolumbar and lumbar OF were enrolled in the study. The mean Charlson comorbidity index (CCI) was >6, indicating a poor baseline reserve (9.4 ± 1.9), while cardiovascular diseases were the most prevalent among comorbidities. The mean surgical duration was 231.6 ± 89.3 min, with a mean blood loss of 694.4± 200.3 mL. The in-hospital was 8.6% and 90-day mortality rates at 11.4%. Two patients underwent revision surgery for deep wound infection. Intraoperative and postoperative radiography and computed tomography (CT) imaging revealed correct screw placement. Proper alignment of the thoracolumbar spine was achieved in all the patients. Unique risk factors for mortality included the presence of comorbidities and the occurrence of postoperative complications. Conclusions Emergent instrumentation in patients with acute onset of neurological decline and potentially unstable spines due to thoracolumbar and lumbar OF improved functional outcomes at discharge. Age should not be a determinant of whether to perform surgery.

Published
2023
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5. Anterior cervical discectomy and fusion with plate versus posterior screw fixation after traumatic subaxial fractures in octogenarians: complications and outcomes with a 2-year follow-up

Author

Pavlina Lenga, Gelo Gülec, Karl Kiening, Andreas W. Unterberg, and Basem Ishak

Subjects
Surgery, Neurology (clinical)
Abstract

Introduction Surgical intervention for management of spinal instability after traumatic subaxial fractures in octogenarians requires a clear consensus on optimal treatments. This study aimed to provide a guide for more efficient management through comparison and assessment of clinical outcomes and complications of anterior cervical discectomy and fusion with plate (pACDF) and posterior decompression fusion (PDF) instrumentation alone in patients aged 80 years. Methods A single institution retrospective review of electronic medical records was undertaken between September 2005 and December 2021. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). Logistic regression was used to identify potential risk factors for ACDF complications. Results The rate of comorbidities were similarly high between the pACDF (n=13) and PDF (n=15) groups (pACDF: 8.7 ± 2.4 points vs. 8.5 ± 2.3 points; p=0.555). Patients in the PDF group had significantly longer surgical duration (235 ± 58.4 min vs. 182.5 ± 32.1 min; ppp>0.05). Motor scores (MS) improved significantly after surgery in both groups (pACDF: preOP MS: 75.3 ± 11.1 vs. postOP MS: 82.4 ± 10.1; ppp=0.005) and larger volume of blood loss (odds ratio 1.5, 95% confidence interval 1.2–2.2; p=0.003). Conclusions Both pACDF and PDF can be considered safe treatment strategies for octogenarians with a poor baseline profile and subaxial fractures as they lead to patients substantial neurological improvements, and they are accompanied with low morbidity and mortality rates. Operation duration and intraoperative blood loss should be minimized to increase the degree of neurological recovery in octogenarian patients.

Published
2023
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7. Tensor- and high-resolution fiber tractography for the delineation of the optic radiation and corticospinal tract in the proximity of intracerebral lesions: a reproducibility and repeatability study

Author

Pavlina Lenga, Moritz Scherer, Peter Neher, Jessica Jesser, Irada Pflüger, Klaus Maier-Hein, Andreas W. Unterberg, and Daniela Becker

Subjects
Surgery, Neurology (clinical)
Abstract

Purpose Fiber tracking (FT) is used in neurosurgical planning for the resection of lesions in proximity to fiber pathways, as it contributes to a substantial amelioration of postoperative neurological impairments. Currently, diffusion-tensor imaging (DTI)-based FT is the most frequently used technique; however, sophisticated techniques such as Q-ball (QBI) for high-resolution FT (HRFT) have suggested favorable results. Little is known about the reproducibility of both techniques in the clinical setting. Therefore, this study aimed to examine the intra- and interrater agreement for the depiction of white matter pathways such as the corticospinal tract (CST) and the optic radiation (OR). Methods Nineteen patients with eloquent lesions in the proximity of the OR or CST were prospectively enrolled. Two different raters independently reconstructed the fiber bundles by applying probabilistic DTI- and QBI-FT. Interrater agreement was evaluated from the comparison between results obtained by the two raters on the same data set acquired in two independent iterations at different timepoints using the Dice Similarity Coefficient (DSC) and the Jaccard Coefficient (JC). Likewise, intrarater agreement was determined for each rater comparing individual results. Results DSC values showed substantial intrarater agreement based on DTI-FT (rater 1: mean 0.77 (0.68–0.85); rater 2: mean 0.75 (0.64–0.81); p = 0.673); while an excellent agreement was observed after the deployment of QBI-based FT (rater 1: mean 0.86 (0.78–0.98); rater 2: mean 0.80 (0.72–0.91); p = 0.693). In contrast, fair agreement was observed between both measures for the repeatability of the OR of each rater based on DTI-FT (rater 1: mean 0.36 (0.26–0.77); rater 2: mean 0.40 (0.27–0.79), p = 0.546). A substantial agreement between the measures was noted by applying QBI-FT (rater 1: mean 0.67 (0.44–0.78); rater 2: mean 0.62 (0.32–0.70), 0.665). The interrater agreement was moderate for the reproducibility of the CST and OR for both DSC and JC based on DTI-FT (DSC and JC ≥ 0.40); while a substantial interrater agreement was noted for DSC after applying QBI-based FT for the delineation of both fiber tracts (DSC > 0.6). Conclusions Our findings suggest that QBI-based FT might be a more robust tool for the visualization of the OR and CST adjacent to intracerebral lesions compared with the common standard DTI-FT. For neurosurgical planning during the daily workflow, QBI appears to be feasible and less operator-dependent.

Published
2023
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10. Recharge PSYCH: A Study on Rechargeable Implantable Pulse Generators in Deep Brain Stimulation for Psychiatric Disorders

Author

Martin Jakobs, Mohammad Mehdi Hajiabadi, David Hernán Aguirre-Padilla, Peter Giaccobe, Andreas W. Unterberg, and Andres M. Lozano

Subjects
Surgery, Neurology (clinical)
Abstract

Rechargeable implantable pulse generators (r-IPGs) for deep brain stimulation (DBS) promise longer battery life and fewer replacement surgeries versus non-rechargeable systems. Long-term data on the effects of recharging in patients who received DBS for psychiatric indications is limited. The Recharge PSYCH trial is the first study that included DBS patients with psychiatric disorders treated with different r-IPG models.Standardized questionnaires were sent to all psychiatric DBS patients with an r-IPG implanted at the time of the study. The primary endpoint was convenience of recharging. Secondary endpoints were rate of user confidence and rate of usage-related complications, as well as charge burden (defined as minutes per week needed to recharge).Data sets of n = 21 patients were eligible for data analysis. At the time of the survey patients were implanted with the r-IPG for a mean 31.8 ± 22.4 months. Prior to being implanted with an r-IPG, patients had undergone a median of 3 IPG replacements. The overall convenience of the charging process was rated as "easy" with a median of 8.0 out of 10.0 points. 33.3% of patients experienced situations in which the device could not be successfully recharged. In 38.1% of patients, therapy with the r-IPG was interrupted unintentionally. The average charge burden was 286 ± 22.4 minutes per week.Patients with psychiatric disorders rated the recharging process as "easy", but with a significantly higher charge burden and usage-related complication rates compared to published data on movement disorder DBS patients.

Published
2023
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11. Clinical outcome following surgical resection and radiotherapy in adult patients with pleomorphic xanthoastrocytoma as defined by DNA methylation profiling

Author

Maximilian Deng, Felix Hinz, Semi Harrabi, Dominik Sturm, Martin Sill, Andrey Korshunov, Tanja Eichkorn, Juliane Hörner-Rieber, Klaus Herfarth, Christine Jungk, Andreas Unterberg, Stefan Pfister, Wolfgang Wick, Andreas von Deimling, David Jones, Jürgen Debus, Felix Sahm, and Laila König

Subjects
Medicine (miscellaneous)
Abstract

Background Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs—in light of the diverse selected treatment regimes. Methods A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed. Results Divergent initial histological diagnoses were encountered in 40.7%. There was no significant difference in local progression-free (PFS) and overall survival (OS) following gross total or subtotal resection. Postoperative radiotherapy was completed in 81% (22/27) following surgical intervention. Local PFS was 54.4% (95% CI: 35.3–84.0%) and OS was 81.3% (95% CI: 63.8–100%) after 3 years following postoperative radiotherapy. Initial relapses post-radiotherapy were primarily located in the previous tumor location and/or the planning target volume (PTV) (12/13). All patients in our cohort demonstrated the prognostically favorable pTERT-wildtype mcPXA. Conclusion Our study demonstrated that adult patients with mcPXAs display a worse progression-free survival compared to the reported WHO grade 2 PXAs. Future matched-pair analyses are required with a non-irradiated cohort to elucidate the benefit of postoperative radiotherapy in adult patients with mcPXAs.

Published
2023
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12. Isocitrate-dehydrogenase-mutant lower grade glioma in elderly patients: treatment and outcome in a molecularly characterized contemporary cohort

Author

P. Dao Trong, M. Gluszak, D. Reuss, A. von Deimling, A. Wick, L. König, J. Debus, C. Herold-Mende, A. Unterberg, and C. Jungk

Subjects
Cancer Research, Neurology, Oncology, Neurology (clinical)
Abstract

Purpose Lower-grade glioma (LGG) is rare among patients above the age of 60 (“elderly”). Previous studies reported poor outcome, likely due to the inclusion of isocitrate dehydrogenase (IDH) wildtype astrocytomas and advocated defensive surgical and adjuvant treatment. This study set out to question this paradigm analyzing a contemporary cohort of patients with IDH mutant astrocytoma and oligodendroglioma WHO grade 2 and 3. Methods Elderly patients treated in our department for a supratentorial, hemispheric LGG between 2009 and 2019 were retrospectively analyzed for patient-, tumor- and treatment-related factors and progression-free survival (PFS) and compared to patients aged under 60. Inclusion required the availability of subtype-defining molecular data and pre- and post-operative tumor volumes. Results 207 patients were included, among those 21 elderlies (10%). PFS was comparable between elderly and younger patients (46 vs. 54 months; p = 0.634). Oligodendroglioma was more common in the elderly (76% vs. 46%; p = 0.011). Most patients underwent tumor resection (elderly: 81% vs. younger: 91%; p = 0.246) yielding comparable residual tumor volumes (elderly: 7.8 cm3; younger: 4.1 cm3; p = 0.137). Adjuvant treatment was administered in 76% of elderly and 61% of younger patients (p = 0.163). Uni- and multi-variate survival analyses identified a tumor crossing the midline, surgical strategy, and pre- and post-operative tumor volumes as prognostic factors. Conclusion Elderly patients constitute a small fraction of molecularly characterized LGGs. In contrast to previous reports, favorable surgical and survival outcomes were achieved in our series comparable to those of younger patients. Thus, intensified treatment including maximal safe resection should be advocated in elderly patients whenever feasible.

Published
2023
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13. ACDF versus corpectomy in octogenarians with cervical epidural abscess: early complications and outcomes with 2 years of follow-up

Author

Pavlina Lenga, Gelo Gülec, Awais Akbar Bajwa, Mohammed Issa, Karl Kiening, Andreas W. Unterberg, and Basem Ishak

Subjects
Surgery, Neurology (clinical)
Abstract

Purpose Cervical spinal epidural abscess (CSEA) is a rare condition, manifesting as rapid neurological deterioration and leading to early neurological deficits. Its management remains challenging, especially in patients older than 80 years. Therefore, we aimed to compare the clinical course and determine morbidity and mortality rates after anterior cervical discectomy and fusion (ACDF) versus corpectomy in octogenarians with ventrally located CSEA at two levels. Methods In this single-center retrospective review, we obtained the following from electronic medical records between September 2005 and December 2021: patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality rate. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). Results Over 16 years, 15 patients underwent ACDF, and 16 patients underwent corpectomy with plate fixation. Between the two groups, patients who underwent corpectomy had a significantly poorer baseline reserve (9.0 ± 2.6 vs. 10.8 ± 2.7; p = 0.004) and had a longer hospitalization period (16.4 ± 13.1 vs. 10.0 ± 5.3 days; p = 0.004) since corpectomy lasted significantly longer (229.6 ± 74.9 min vs. 123.9 ± 47.5 min; p Conclusions We showed that both ACDF and corpectomy for ventrally located CSEA can be considered as safe treatment strategies for patients aged 80 years and above. However, the surgical approach should be carefully weighed and discussed with the patients and their relatives.

Published
2023
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14. Adverse events in neurosurgery: a comprehensive single-center analysis of a prospectively compiled database

Author

Philip Dao Trong, Arturo Olivares, Ahmed El Damaty, and Andreas Unterberg

Subjects
Surgery, Neurology (clinical)
Abstract

Purpose To prospectively identify and quantify neurosurgical adverse events (AEs) in a tertiary care hospital. Methods From January 2021 to December 2021, all patients treated in our department received a peer-reviewed AE-evaluation form at discharge. An AE was defined as any event after surgery that resulted in an undesirable clinical outcome, which is not caused by the underlying disease, that prolonged patient stay, resulted in readmission, caused a new neurological deficit, required revision surgery or life-saving intervention, or contributed to death. We considered AEs occurring within 30 days after discharge. AEs were categorized in wound event, cerebrospinal fluid (CSF) event, CSF shunt malfunction, post-operative infection, malpositioning of implanted material, new neurological deficit, rebleeding, and surgical goal not achieved and non-neurosurgical AEs. Results 2874 patients were included. Most procedures were cranial (45.1%), followed by spinal (33.9%), subdural (7.7%), CSF (7.0%), neuromodulation (4.0%), and other (2.3%). In total, there were 621 AEs shared by 532 patients (18.5%). 80 (2.8%) patients had multiple AEs. Most AEs were non-neurosurgical (222; 8.1%). There were 172 (6%) revision surgeries. Patients receiving cranial interventions had the most AEs (19.1%) although revision surgery was only necessary in 3.1% of patients. Subdural interventions had the highest revision rate (12.6%). The majority of fatalities was admitted as an emergency (81/91 patients, 89%). Ten elective patients had lethal complications, six of them related to surgery (0.2%). Conclusion This study presents the one-year results of a prospectively compiled AE database. Neurosurgical AEs arose in one in five patients. Although the need for revision surgery was low, the rate of AEs highlights the importance of a systematic AE database to deliver continued high-quality in a high-volume center.

Published
2023
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15. Analysis of intracranial pressure pulse waveform in traumatic brain injury patients: a CENTER-TBI study

Author

Agnieszka Uryga, Arkadiusz Ziółkowski, Agnieszka Kazimierska, Agata Pudełko, Cyprian Mataczyński, Erhard W. Lang, Marek Czosnyka, Magdalena Kasprowicz, Audny Anke, Ronny Beer, Bo-Michael Bellander, Erta Beqiri, Andras Buki, Manuel Cabeleira, Marco Carbonara, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Endre Czeiter, Bart Depreitere, Ari Ercole, Shirin Frisvold, Raimund Helbok, Stefan Jankowski, Danile Kondziella, Lars-Owe Koskinen, Ana Kowark, David K. Menon, Geert Meyfroidt, Kirsten Moeller, David Nelson, Anna Piippo-Karjalainen, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Saulius Rocka, Rolf Rossaint, Juan Sahuquillo, Oliver Sakowitz, Peter Smielewski, Nino Stocchetti, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Olli Tenovuo, Andreas Unterberg, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, Stefan Wolf, Alexander Younsi, Frederick A. Zeiler, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, American asssociation of neurological ssurgeons, Uryga, A, Ziółkowski, A, Kazimierska, A, Pudełko, A, Mataczyński, C, Lang, E, Czosnyka, M, Kasprowicz, M, Citerio, G, Ročka, Saulius, and Tamošuitis, Tomas

Subjects
intracranial pressure, pulse amplitude, pulse shape index, clinical outcome, spectral analysis, morphological analysis, traumatic brain injury, spectral analysi, morphological analysi, General Medicine
Abstract

OBJECTIVE Intracranial pressure (ICP) pulse waveform analysis may provide valuable information about cerebrospinal pressure-volume compensation in patients with traumatic brain injury (TBI). The authors applied spectral methods to analyze ICP waveforms in terms of the pulse amplitude of ICP (AMP), high frequency centroid (HFC), and higher harmonics centroid (HHC) and also used a morphological classification approach to assess changes in the shape of ICP pulse waveforms using the pulse shape index (PSI). METHODS The authors included 184 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Sub-Study in the analysis. HFC was calculated as the average power-weighted frequency within the 4- to 15-Hz frequency range of the ICP power density spectrum. HHC was defined as the center of mass of the ICP pulse waveform harmonics from the 2nd to the 10th. PSI was defined as the weighted sum of artificial intelligence–based ICP pulse class numbers from 1 (normal pulse waveform) to 4 (pathological waveform). RESULTS AMP and PSI increased linearly with mean ICP. HFC increased proportionally to ICP until the upper breakpoint (average ICP of 31 mm Hg), whereas HHC slightly increased with ICP and then decreased significantly when ICP exceeded 25 mm Hg. AMP (p < 0.001), HFC (p = 0.003), and PSI (p < 0.001) were significantly greater in patients who died than in patients who survived. Among those patients with low ICP (< 15 mm Hg), AMP, PSI, and HFC were greater in those with poor outcome than in those with good outcome (all p < 0.001). CONCLUSIONS Whereas HFC, AMP, and PSI could be used as predictors of mortality, HHC may potentially serve as an early warning sign of intracranial hypertension. Elevated HFC, AMP, and PSI were associated with poor outcome in TBI patients with low ICP.

Published
2022
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16. Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury

Author

Bockhop, Fabian, Zeldovich, Marina, Cunitz, Katrin, Van Praag, Dominique, van der Vlegel, Marjolein, Beissbarth, Tim, Hagmayer, York, von Steinbuechel, Nicole, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, L. Gruen, Russell, Gupta, Deepak, A. Haagsma, Juanita, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, G. Kolias, Angelos, Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, I.R. Maas, Andrew, Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Røe, Cecilie, Røise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, RueckertMartin Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Steven Taylor, Mark, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Maria Tudora, Cristina, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, Naalt, Joukje van der, T.J.M. van Dijck, Jeroen, van Erp, Inge A. M., van Essen, Thomas A., Hecke, Wim Van, van Heugten, Caroline, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, K.W. Wang, Kevin, Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Apollo - University of Cambridge Repository, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, „Springer Nature' grupė, Ročka, Saulius, Tamošuitis, Tomas, CTR-TBI Participants Investigators, Molecular Neuroscience and Ageing Research (MOLAR), Public Health, Amrein, Krisztina, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Andelic, Nada, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Andreassen, Lasse, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Anke, Audny, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Antoni, Anna, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Audibert, Gérard, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Azouvi, Philippe, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Azzolini, Maria Luisa, Ripatti, Samuli, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Bartels, Ronald, Rueckert, Martin, Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Barzó, Pál, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Beauvais, Romuald, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Beer, Ronny, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Bellander, Bo-Michael, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. 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W., Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Berardino, Maurizio, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Åkerlund, Cecilia, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Bockhop, F, Zeldovich, M, Cunitz, K, Van Praag, D, van der Vlegel, M, Beissbarth, T, Hagmayer, Y, von Steinbuechel, N, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini Maria, L, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi Maria, R, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper Jamie, D, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin Valery, L, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Guoyi Gao, N, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, A., G, Gratz, J, Gravesteijn, B, Grossi, F, L., G, Gupta, D, A., H, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, J., H, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, G., K, Kompanje, E, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, I. 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J. M., V, van Erp Inge, A, van Essen Thomas, A, Hecke Wim, V, van Heugten, C, van Veen, E, Vande Vyvere, T, van Wijk Roel, P, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa Paul, M, Vik, A, Vilcinis, R, Volovici, V, von Steinbüchel, N, Voormolen, D, Vulekovic, P, K. W., W, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler Frederick, A, Zelinkova, V, Ziverte, A, Zoerle, T, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Statistical and population genetics, Clinicum, Helsinki University Hospital Area, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics

Subjects
Post-Traumatic/psychology, Multidisciplinary, Traumatic/complications, Brain Injuries, Traumatic/complications, 3124 Neurology and psychiatry, Diagnostic and Statistical Manual of Mental Disorder, Stress Disorders, Post-Traumatic/psychology, Checklist, Diagnostic and Statistical Manual of Mental Disorders, Stress Disorders, Post-Traumatic, Brain Injuries, Brain Injuries, Traumatic, Humans, Human medicine, Human, Stress Disorders, Language
Abstract

Scientific reports 12, 16571 (2022). doi:10.1038/s41598-022-20170-2, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Published
2022
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17. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI)

Author

Eveline Janine Anna Wiegers, Hester Floor Lingsma, Jilske Antonia Huijben, David James Cooper, Giuseppe Citerio, Shirin Frisvold, Raimund Helbok, Andrew Ian Ramsay Maas, David Krishna Menon, Elizabeth Madeleine Moore, Nino Stocchetti, Diederik Willem Dippel, Ewout Willem Steyerberg, Mathieu van der Jagt, Joanne Brooker, Peter Bragge, Jeffrey Rosenfeld, Jamie D. Cooper, Ronny Beer, Herbert Schoechl, Martin Rusnák, Elisabeth Schwendenwein, Anna Antoni, Véronique De Keyser, Tomas Menovsky, Dominique Van Praag, Andrew I.R. Maas, Gregory Van der Steen, Paul M. Parizel, Thijs Vande Vyvere, Bart Depreitere, Wim Van Hecke, Jan Verheyden, Benoit Misset, Didier Ledoux, Steven Laureys, Alexandre Ghuysen, Hugues Maréchal, Guy-Loup Dulière, Guoyi Gao, Ji-yao Jiang, Daniel Kondziella, Martin Fabricius, Rico Frederik Schou, Morten Blaabjerg, Christina Rosenlund, Anna Piippo-Karjalainen, Rahul Raj, Matti Pirinen, Samuli Ripatti, Aarno Palotie, Peter Ylén, Jussi P. Posti, Olli Tenovuo, Riikka Takala, Jean-François Payen, Emmanuel Vega, Aurelie Lejeune, Gérard Audibert, Vincent Degos, Habib Benali, Damien Galanaud, Vincent Perlbarg, Louis Puybasset, Philippe Azouvi, Valerie Legrand, Claire Dahyot-Fizelier, Rolf Rossaint, Mark Steven Coburn, Ana Kowark, Hans Clusmann, Jens Dreier, Stefan Wolf, Peter Vajkoczy, Marc Maegele, Johannes Gratz, Nadine Schäfer, Rolf Lefering, Amra Covic, Nicole von Steinbüchel, Silke Schmidt, Monika Bullinger, Alexander Younsi, Andreas Unterberg, Julia Mattern, Oliver Sakowitz, Renan Sanchez-Porras, Natascha Perera, Romuald Beauvais, Janos Sandor, Endre Czeiter, Andras Buki, Erzsébet Ezer, Zoltán Vámos, Béla Melegh, Viktória Tamás, Abayomi Sorinola, Noémi Kovács, József Nyirádi, Krisztina Amrein, Pál Barzó, Deepak Gupta, Leon Levi, Guy Rosenthal, Alex Furmanov, Costanza Martino, Luigi Beretta, Maria Rosa Calvi, Maria Luisa Azzolini, Emiliana Calappi, Tommaso Zoerle, Fabrizio Ortolano, Marco Carbonara, Alessio Caccioppola, Alessia Vargiolu, Arturo Chieregato, Giorgio Chevallard, Francesco Della Corte, Francesca Grossi, Sandra Rossi, Paolo Persona, Maurizio Berardino, Simona Cavallo, Malinka Rambadagalla, Agate Ziverte, Lelde Giga, Egils Valeinis, Rimantas Vilcinis, Tomas Tamosuitis, Saulius Rocka, Arminas Ragauskas, Joukje van der Naalt, Bram Jacobs, Ewout W. Steyerberg, Ronald Bartels, Hugo den Boogert, Erwin Kompanje, Marjolijn Timmers, Kelly Foks, Iain Haitsma, Victor Volovici, Juanita A. Haagsma, Ana Mikolic, Hester Lingsma, Kimberley Velt, Jilske Huijben, Daphne Voormolen, Daan Nieboer, Eveline Wiegers, Charlie Sewalt, Benjamin Gravesteijn, Suzanne Polinder, Dick Tibboel, Roel van Wijk, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wilco Peul, Guus Schoonman, Kelly Jones, Valery L. Feigin, Braden Te Ao, Alice Theadom, Eirik Helseth, Cecilie Roe, Olav Roise, Nada Andelic, Lasse Andreassen, Audny Anke, Anne Vik, Toril Skandsen, Horia Ples, Cristina Maria Tudora, Ancuta Negru, Peter Vulekovic, Đula Đilvesi, Mladen Karan, Jagoš Golubovic, Veronika Rehorcíková, Mark Steven Taylor, Alexandra Brazinova, Marek Majdan, Juan Sahuquillo, Andreea Radoi, Guillermo Carbayo Lozano, Inigo Pomposo, Alfonso Lagares, Pedro A. Gomez, Ana M. Castaño-León, Pablo Gagliardo, Matej Oresic, Bo-Michael Bellander, Linda Lanyon, Pradeep George, Visakh Muraleedharan, David Nelson, Cecilia Ackerlund, Lars-Owe Koskinen, Nina Sundström, Camilla Brorsson, Antonio Belli, Alex Manara, Matt Thomas, Marek Czosnyka, Peter Smielewski, Manuel Cabeleira, Jonathan Coles, Sylvia Richardson, Frederick A. Zeiler, Emmanuel Stamatakis, Guy Williams, David Menon, Ari Ercole, Abhishek Dixit, Virginia Newcombe, Sophie Richter, Charles McFadyen, Peter J. Hutchinson, Angelos G. Kolias, Hadie Adams, Marta Correia, Jonathan Rhodes, William Stewart, Catherine McMahon, Daniel Rueckert, Ben Glocker, Christos Tolias, Helen Dawes, Patrick Esser, Caroline van Heugten, Nicola Curry, Simon Stanworth, Fiona Lecky, Olubukola Otesile, Faye Johnson, Paul Dark, Stefan Jankowski, Roger Lightfoot, Lindsay Wilson, Lindsay Horton, Robert Stevens, Jonathan Rosand, Geoffrey Manley, Mike Jarrett, Vibeke Brinck, Kevin K.W. Wang, Zhihui Yang, Paul M. Vespa, Russell L. Gruen, Peter Cameron, Emma Donoghue, Dashiell Gantner, Russel Gruen, Lynette Murray, Jeffrey V. Rosenfeld, Dinesh Varma, Tony Trapani, Shirley Vallance, Cristopher MacIsaac, Andrea Jordan, Wiegers, E. J. A., Lingsma, H. F., Huijben, J. A., Cooper, D. J., Citerio, G., Frisvold, S., Helbok, R., Maas, A. I. R., Menon, D. K., Moore, E. M., Stocchetti, N., Dippel, D. W., Steyerberg, E. W., van der Jagt, M., Brooker, J., Bragge, P., Rosenfeld, J., Cooper, J. D., Beer, R., Schoechl, H., Rusnak, M., Schwendenwein, E., Antoni, A., De Keyser, V., Menovsky, T., Van Praag, D., Van der Steen, G., Parizel, P. M., Vande Vyvere, T., Depreitere, B., Van Hecke, W., Verheyden, J., Misset, B., Ledoux, D., Laureys, S., Ghuysen, A., Marechal, H., Duliere, G. -L., Gao, G., Jiang, J. -Y., Kondziella, D., Fabricius, M., Schou, R. F., Blaabjerg, M., Rosenlund, C., Piippo-Karjalainen, A., Raj, R., Pirinen, M., Ripatti, S., Palotie, A., Ylen, P., Posti, J. P., Tenovuo, O., Takala, R., Payen, J. -F., Vega, E., Lejeune, A., Audibert, G., Degos, V., Benali, H., Galanaud, D., Perlbarg, V., Puybasset, L., Azouvi, P., Legrand, V., Dahyot-Fizelier, C., Rossaint, R., Coburn, M. S., Kowark, A., Clusmann, H., Dreier, J., Wolf, S., Vajkoczy, P., Maegele, M., Gratz, J., Schafer, N., Lefering, R., Covic, A., von Steinbuchel, N., Schmidt, S., Bullinger, M., Younsi, A., Unterberg, A., Mattern, J., Sakowitz, O., Sanchez-Porras, R., Perera, N., Beauvais, R., Sandor, J., Czeiter, E., Buki, A., Ezer, E., Vamos, Z., Melegh, B., Tamas, V., Sorinola, A., Kovacs, N., Nyiradi, J., Amrein, K., Barzo, P., Gupta, D., Levi, L., Rosenthal, G., Furmanov, A., Martino, C., Beretta, L., Calvi, M. R., Azzolini, M. L., Calappi, E., Zoerle, T., Ortolano, F., Carbonara, M., Caccioppola, A., Vargiolu, A., Chieregato, A., Chevallard, G., Della Corte, F., Grossi, F., Rossi, S., Persona, P., Berardino, M., Cavallo, S., Rambadagalla, M., Ziverte, A., Giga, L., Valeinis, E., Vilcinis, R., Tamosuitis, T., Rocka, S., Ragauskas, A., van der Naalt, J., Jacobs, B., Bartels, R., den Boogert, H., Kompanje, E., Timmers, M., Foks, K., Haitsma, I., Volovici, V., Haagsma, J. A., Mikolic, A., Lingsma, H., Velt, K., Huijben, J., Voormolen, D., Nieboer, D., Wiegers, E., Sewalt, C., Gravesteijn, B., Polinder, S., Tibboel, D., van Wijk, R., van Dijck, J. T. J. M., van Essen, T. A., Peul, W., Schoonman, G., Jones, K., Feigin, V. L., Te Ao, B., Theadom, A., Helseth, E., Roe, C., Roise, O., Andelic, N., Andreassen, L., Anke, A., Vik, A., Skandsen, T., Ples, H., Tudora, C. M., Negru, A., Vulekovic, P., Dilvesi, D., Karan, M., Golubovic, J., Rehorcikova, V., Taylor, M. S., Brazinova, A., Majdan, M., Sahuquillo, J., Radoi, A., Carbayo Lozano, G., Pomposo, I., Lagares, A., Gomez, P. A., Castano-Leon, A. M., Gagliardo, P., Oresic, M., Bellander, B. -M., Lanyon, L., George, P., Muraleedharan, V., Nelson, D., Ackerlund, C., Koskinen, L. -O., Sundstrom, N., Brorsson, C., Belli, A., Manara, A., Thomas, M., Czosnyka, M., Smielewski, P., Cabeleira, M., Coles, J., Richardson, S., Zeiler, F. A., Stamatakis, E., Williams, G., Menon, D., Ercole, A., Dixit, A., Newcombe, V., Richter, S., Mcfadyen, C., Hutchinson, P. J., Kolias, A. G., Adams, H., Correia, M., Rhodes, J., Stewart, W., Mcmahon, C., Rueckert, D., Glocker, B., Tolias, C., Dawes, H., Esser, P., van Heugten, C., Curry, N., Stanworth, S., Lecky, F., Otesile, O., Johnson, F., Dark, P., Jankowski, S., Lightfoot, R., Wilson, L., Horton, L., Stevens, R., Rosand, J., Manley, G., Jarrett, M., Brinck, V., Wang, K. K. W., Yang, Z., Vespa, P. M., Gruen, R. L., Cameron, P., Donoghue, E., Gantner, D., Gruen, R., Murray, L., Rosenfeld, J. V., Varma, D., Trapani, T., Vallance, S., Macisaac, C., Jordan, A., Public Health, Neurology, Intensive Care, Neurosurgery, Erasmus MC other, Pediatric Surgery, CENTER-TBI Collaboration Group, OzENTER-TBI Collaboration Group, Molecular Neuroscience and Ageing Research (MOLAR), Psychology 3, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Wiegers, E, Lingsma, H, Huijben, J, Cooper, D, Citerio, G, Frisvold, S, Helbok, R, Maas, A, Menon, D, Moore, E, Stocchetti, N, Dippel, D, Steyerberg, E, van der Jagt, M, Brooker, J, Bragge, P, Rosenfeld, J, Cooper, J, Beer, R, Schoechl, H, Rusnák, M, Schwendenwein, E, Antoni, A, De Keyser, V, Menovsky, T, Van Praag, D, Van der Steen, G, Parizel, P, Vande Vyvere, T, Depreitere, B, Van Hecke, W, Verheyden, J, Misset, B, Ledoux, D, Laureys, S, Ghuysen, A, Maréchal, H, Dulière, G, Gao, G, Jiang, J, Kondziella, D, Fabricius, M, Schou, R, Blaabjerg, M, Rosenlund, C, Piippo-Karjalainen, A, Raj, R, Pirinen, M, Ripatti, S, Palotie, A, Ylén, P, Posti, J, Tenovuo, O, Takala, R, Payen, J, Vega, E, Lejeune, A, Audibert, G, Degos, V, Benali, H, Galanaud, D, Perlbarg, V, Puybasset, L, Azouvi, P, Legrand, V, Dahyot-Fizelier, C, Rossaint, R, Coburn, M, Kowark, A, Clusmann, H, Dreier, J, Wolf, S, Vajkoczy, P, Maegele, M, Gratz, J, Schäfer, N, Lefering, R, Covic, A, von Steinbüchel, N, Schmidt, S, Bullinger, M, Younsi, A, Unterberg, A, Mattern, J, Sakowitz, O, Sanchez-Porras, R, Perera, N, Beauvais, R, Sandor, J, Czeiter, E, Buki, A, Ezer, E, Vámos, Z, Melegh, B, Tamás, V, Sorinola, A, Kovács, N, Nyirádi, J, Amrein, K, Barzó, P, Gupta, D, Levi, L, Rosenthal, G, Furmanov, A, Martino, C, Beretta, L, Calvi, M, Azzolini, M, Calappi, E, Zoerle, T, Ortolano, F, Carbonara, M, Caccioppola, A, Vargiolu, A, Chieregato, A, Chevallard, G, Della Corte, F, Grossi, F, Rossi, S, Persona, P, Berardino, M, Cavallo, S, Rambadagalla, M, Ziverte, A, Giga, L, Valeinis, E, Vilcinis, R, Tamosuitis, T, Rocka, S, Ragauskas, A, van der Naalt, J, Jacobs, B, Bartels, R, den Boogert, H, Kompanje, E, Timmers, M, Foks, K, Haitsma, I, Volovici, V, Haagsma, J, Mikolic, A, Velt, K, Voormolen, D, Nieboer, D, Sewalt, C, Gravesteijn, B, Polinder, S, Tibboel, D, van Wijk, R, van Dijck, J, van Essen, T, Peul, W, Schoonman, G, Jones, K, Feigin, V, Te Ao, B, Theadom, A, Helseth, E, Roe, C, Roise, O, Andelic, N, Andreassen, L, Anke, A, Vik, A, Skandsen, T, Ples, H, Tudora, C, Negru, A, Vulekovic, P, Đilvesi, Đ, Karan, M, Golubovic, J, Rehorcíková, V, Taylor, M, Brazinova, A, Majdan, M, Sahuquillo, J, Radoi, A, Carbayo Lozano, G, Pomposo, I, Lagares, A, Gomez, P, Castaño-León, A, Gagliardo, P, Oresic, M, Bellander, B, Lanyon, L, George, P, Muraleedharan, V, Nelson, D, Ackerlund, C, Koskinen, L, Sundström, N, Brorsson, C, Belli, A, Manara, A, Thomas, M, Czosnyka, M, Smielewski, P, Cabeleira, M, Coles, J, Richardson, S, Zeiler, F, Stamatakis, E, Williams, G, Ercole, A, Dixit, A, Newcombe, V, Richter, S, Mcfadyen, C, Hutchinson, P, Kolias, A, Adams, H, Correia, M, Rhodes, J, Stewart, W, Mcmahon, C, Rueckert, D, Glocker, B, Tolias, C, Dawes, H, Esser, P, van Heugten, C, Curry, N, Stanworth, S, Lecky, F, Otesile, O, Johnson, F, Dark, P, Jankowski, S, Lightfoot, R, Wilson, L, Horton, L, Stevens, R, Rosand, J, Manley, G, Jarrett, M, Brinck, V, Wang, K, Yang, Z, Vespa, P, Gruen, R, Cameron, P, Donoghue, E, Gantner, D, Murray, L, Varma, D, Trapani, T, Vallance, S, Macisaac, C, and Jordan, A

Subjects
medicine.medical_specialty, Fluid balance and outcome in critically ill patients traumatic brain injury, Icu mortality, Traumatic brain injury, Critically ill, business.industry, INTRACRANIAL-PRESSURE, Glasgow Outcome Scale, Odds ratio, medicine.disease, GUIDELINES, Intensive care unit, law.invention, law, Emergency medicine, medicine, MANAGEMENT, Observational study, Neurology (clinical), Human medicine, business, Balance (ability)
Abstract

Background Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.Methods We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.Findings 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1middot48 L (IQR 1middot12 to 2middot09) to 4middot23 L (3middot78 to 4middot94) across centres. The median of the mean daily fluid balance ranged from -0middot85 L (IQR -1middot51 to -0middot49) to 1middot13 L (0middot99 to 1middot37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1middot10 [95% CI 1middot07 to 1middot12] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot02 to 1middot05] per 0middot1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1middot05 [1middot03 to 1middot06] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot03 to 1middot04] per 1-point decrease of the GOSE per 0middot1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1middot17 [95% CI 1middot05 to 1middot29]) and worse functional outcome (1middot07 [1middot02 to 1middot13]), but higher fluid input was not associated with ICU mortality (OR 0middot95 [0middot90 to 1middot00]) or worse functional outcome (1middot01 [0middot98 to 1middot03]).Interpretation In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Published
2021
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19. Surgical Management of Spinal Epidural Abscess in Elderly Patients: A Comparative Analysis Between Patients 65–79 Years and ≥80 Years with 3-Year Follow-Up

Author

Pavlina Lenga, Gelo Gülec, Awais Akbar Bajwa, Mohammed Issa, Karl Kiening, Andreas W. Unterberg, and Basem Ishak

Subjects
Surgery, Neurology (clinical)
Abstract

Recently, the incidence of pyogenic vertebral osteomyelitis with spinal epidural abscess (SEA) has increased. However, the most appropriate surgical management remains debatable, especially for older patients. This study aimed to compare the clinical course in older patients aged between 65 and 79 years and those 80 years or older undergoing surgery for SEA.Data on patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality of patients diagnosed with pyogenic vertebral osteomyelitis and SEA between September 2005 and December 2021 were collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index.We enrolled 45 patients aged 65-79 years and 32 patients ≥80 years. Patients ≥80 years had significantly higher rates of Charlson comorbidity index (9.2 ± 2.4) than younger patients (6.5 ± 2.5; P0.001). Arterial hypertension, renal failure, and dementia were significantly more prevalent in octogenarians (P0.05). Patients aged ≥80 years had a significantly longer length of hospitalization, while the intensive care unit stay was similar between groups. In-hospital mortality was significantly greater in those ≥80 years (n = 3, 9.4% vs. n = 0, 0.0%; P = 0.029), whereas no differences in 90-day mortality or 30-day readmission were observed. In the second-stage analysis, significant improvements in blood infection parameters and neurologic status were detected in both groups. Of adverse events, pneumonia occurred significantly more frequently in patients aged ≥80 years.Surgical management leads to significant improvements in both laboratory and clinical parameters in older patients. Nevertheless, a personalized medical approach is mandatory in frail patients, especially octogenarians. A clear discussion regarding the potential risk is unambiguously recommended.

Published
2022
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20. Interleukin-4 Reduces Lesion Volume and Improves Neurological Function in the Acute Phase after Experimental Traumatic Brain Injury in Mice

Author

Johannes, Walter, Olga, Kovalenko, Alexander, Younsi, Martin, Grutza, Andreas, Unterberg, and Klaus, Zweckberger

Subjects
Mice, Inbred C57BL, Mice, Knockout, Disease Models, Animal, Mice, Contusions, Brain Injuries, Traumatic, Animals, Interleukin-4, Neurology (clinical)
Abstract

Little is known about the impact of interleukin-4 (IL-4) on secondary brain damage in the acute phase after experimental traumatic brain injury (TBI). Therefore, we evaluated the effect of IL-4-Knockout (IL-4-KO) on structural damage, as well as functional impairment, in the acute phase after experimental TBI in mice. A total of 28 C57Bl/6 wildtype and 20 C57BL/6

Published
2022
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21. Accuracy of Manual Intracranial Pressure Recording Compared to a Computerized High-Resolution System: A CENTER-TBI Analysis

Author

Zoerle T., Birg T., Carbonara M., Smielewski P., Placek M. M., Zanier E. R., Akerlund C. A. I., Ortolano F., Stocchetti N., Anke A., Beer R., Bellander B. -M., Beqiri E., Buki A., Cabeleira M., Chieregato A., Citerio G., Clusmann H., Czeiter E., Czosnyka M., Depreitere B., Ercole A., Frisvold S., Helbok R., Jankowski S., Kondziella D., Koskinen L. -O., Kowark A., Menon D. K., Meyfroidt G., Moeller K., Nelson D., Piippo-Karjalainen A., Radoi A., Ragauskas A., Raj R., Rhodes J., Rocka S., Rossaint R., Sahuquillo J., Sakowitz O., Sundstrom N., Takala R., Tamosuitis T., Tenovuo O., Unterberg A., Vajkoczy P., Vargiolu A., Vilcinis R., Wolf S., Younsi A., Zeiler F. A., Zoerle, T, Birg, T, Carbonara, M, Smielewski, P, Placek, M, Zanier, E, Akerlund, C, Ortolano, F, Stocchetti, N, Anke, A, Beer, R, Bellander, B, Beqiri, E, Buki, A, Cabeleira, M, Chieregato, A, Citerio, G, Clusmann, H, Czeiter, E, Czosnyka, M, Depreitere, B, Ercole, A, Frisvold, S, Helbok, R, Jankowski, S, Kondziella, D, Koskinen, L, Kowark, A, Menon, D, Meyfroidt, G, Moeller, K, Nelson, D, Piippo-Karjalainen, A, Radoi, A, Ragauskas, A, Raj, R, Rhodes, J, Rocka, S, Rossaint, R, Sahuquillo, J, Sakowitz, O, Sundstrom, N, Takala, R, Tamosuitis, T, Tenovuo, O, Unterberg, A, Vajkoczy, P, Vargiolu, A, Vilcinis, R, Wolf, S, Younsi, A, and Zeiler, F

Subjects
Cerebral perfusion pressure, Traumatic brain injury, Intracranial pressure, Data collection
Abstract

Background: Monitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually on bedside charts; these data have been used in large observational and interventional trials. However, ICP and CPP may change rapidly and frequently, so data recorded in medical charts might underestimate actual ICP and CPP shifts. The aim of this study was to evaluate the accuracy of manual data annotation for proper capturing of ICP and CPP. For this aim, we (1) compared end-hour ICP and CPP values manually recorded (MR) with values recorded continuously by computerized high-resolution (HR) systems and (2) analyzed whether MR ICP and MR CPP are reliable indicators of the burden of intracranial hypertension and low CPP. Methods: One hundred patients were included. First, we compared the MR data with the values stored in the computerized system during the first 7 days after admission. For this point-to-point analysis, we calculated the difference between end-hour MR and HR ICP and CPP. Then we analyzed the burden of high ICP (> 20 mm Hg) and low CPP (< 60 mm Hg) measured by the computerized system, in which continuous data were stored, compared with the pressure–time dose based on end-hour measurements. Results: The mean difference between MR and HR end-hour values was 0.02 mm Hg for ICP (SD 3.86 mm Hg) and 1.54 mm Hg for CPP (SD 8.81 mm Hg). ICP > 20 mm Hg and CPP < 60 mm Hg were not detected by MR in 1.6% and 5.8% of synchronized measurements, respectively. Analysis of the pathological ICP and CPP throughout the recording, however, indicated that calculations based on manual recording seriously underestimated the ICP and CPP burden (in 42% and 28% of patients, respectively). Conclusions: Manual entries fairly represent end-hour HR ICP and CPP. However, compared with a computerized system, they may prove inadequate, with a serious risk of underestimation of the ICP and CPP burden.

Published
2023

22. Towards autoregulation-oriented management after traumatic brain injury: increasing the reliability and stability of the CPPopt algorithm

Author

Beqiri E., Ercole A., Aries M. J. H., Placek M. M., Tas J., Czosnyka M., Stocchetti N., Smielewski P., Anke A., Beer R., Bellander B. -M., Buki A., Cabeleira M., Carbonara M., Chieregato A., Citerio G., Clusmann H., Czeiter E., Depreitere B., Frisvold S., Helbok R., Jankowski S., Kondziella D., Koskinen L. -O., Kowark A., Menon D. K., Meyfroidt G., Moeller K., Nelson D., Piippo-Karjalainen A., Radoi A., Ragauskas A., Raj R., Rhodes J., Rocka S., Rossaint R., Sahuquillo J., Sakowitz O., Sundstrom N., Takala R., Tamosuitis T., Tenovuo O., Unterberg A., Vajkoczy P., Vargiolu A., Vilcinis R., Wolf S., Younsi A., Zeiler F. A., Beqiri, E, Ercole, A, Aries, M, Placek, M, Tas, J, Czosnyka, M, Stocchetti, N, Smielewski, P, Anke, A, Beer, R, Bellander, B, Buki, A, Cabeleira, M, Carbonara, M, Chieregato, A, Citerio, G, Clusmann, H, Czeiter, E, Depreitere, B, Frisvold, S, Helbok, R, Jankowski, S, Kondziella, D, Koskinen, L, Kowark, A, Menon, D, Meyfroidt, G, Moeller, K, Nelson, D, Piippo-Karjalainen, A, Radoi, A, Ragauskas, A, Raj, R, Rhodes, J, Rocka, S, Rossaint, R, Sahuquillo, J, Sakowitz, O, Sundstrom, N, Takala, R, Tamosuitis, T, Tenovuo, O, Unterberg, A, Vajkoczy, P, Vargiolu, A, Vilcinis, R, Wolf, S, Younsi, A, and Zeiler, F

Subjects
Cerebral autoregulation, CPPopt, Traumatic brain injury, Multiwindow weighted approach, Reliability, Stability
Abstract

Purpose: CPPopt denotes a Cerebral Perfusion Pressure (CPP) value at which the Pressure-Reactivity index, reflecting the global state of Cerebral Autoregulation, is best preserved. CPPopt has been investigated as a potential dynamically individualised CPP target in traumatic brain injury patients admitted in intensive care unit. The prospective bedside use of the concept requires ensured safety and reliability of the CPP recommended targets based on the automatically-generated CPPopt. We aimed to: Increase stability and reliability of the CPPopt automated algorithm by fine-tuning; perform outcome validation of the adjusted algorithm in a multi-centre TBI cohort. Methods: ICM + software was used to derive CPPopt and fine-tune the algorithm. Parameters for improvement of the algorithm were selected based on qualitative and quantitative assessment of stability and reliability metrics. Patients enrolled in the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution cohort were included for retrospective validation. Yield and stability of the new algorithm were compared to the previous algorithm using Mann–U test. Area under the curves for mortality prediction at 6 months were compared with the DeLong Test. Results: CPPopt showed higher stability (p < 0.0001), but lower yield compared to the previous algorithm [80.5% (70—87.5) vs 85% (75.7—91.2), p < 0.001]. Deviation of CPPopt could predict mortality with an AUC of [AUC = 0.69 (95% CI 0.59–0.78), p < 0.001] and was comparable with the previous algorithm. Conclusion: The CPPopt calculation algorithm was fine-tuned and adapted for prospective use with acceptable lower yield, improved stability and maintained prognostic power.

Published
2023

23. Anterior Access to the Cervicothoracic Junction via Partial Sternotomy: A Clinical Series Reporting on Technical Feasibility, Postoperative Morbidity, and Early Surgical Outcome

Author

Scherer, Mohammed Issa, Jan-Oliver Neumann, Sameer Al-Maisary, Gerhard Dyckhoff, Moritz Kronlage, Karl L. Kiening, Basem Ishak, Andreas W. Unterberg, and Moritz

Subjects
cervicothoracic junction, anterior thoracic corpectomy, partial sternotomy
Abstract

Surgical access to the cervicothoracic junction (CTJ) is challenging. The aim of this study was to assess technical feasibility, early morbidity, and outcome in patients undergoing anterior access to the CTJ via partial sternotomy. Consecutive cases with CTJ pathology treated via anterior access and partial sternotomy at a single academic center from 2017 to 2022 were retrospectively reviewed. Clinical data, perioperative imaging, and outcome were assessed with regards to the aims of the study. A total of eight cases were analyzed: four (50%) bone metastases, one (12.5%) traumatic instable fracture (B3-AO-Fracture), one (12.5%) thoracic disc herniation with spinal cord compression, and two (25%) infectious pathologic fractures from tuberculosis and spondylodiscitis. The median age was 49.9 years (range: 22–74 y), with a 75% male preponderance. The median Spinal Instability Neoplastic Score (SINS) was 14.5 (IQR: 5; range: 9–16), indicating a high degree of instability in treated cases. Four cases (50%) underwent additional posterior instrumentation. All surgical procedures were performed uneventfully, with no intraoperative complications. The median length of hospital stay was 11.5 days (IQR: 9; range: 6–20), including a median of 1 day in an intensive care unit (ICU). Two cases developed postoperative dysphagia related to stretching and temporary dysfunction of the recurrent laryngeal nerve. Both cases completely recovered at 3 months follow-up. No in-hospital mortality was observed. The radiological outcome was unremarkable in all cases, with no case of implant failure. One case died due to the underlying disease during follow-up. The median follow-up was 2.6 months (IQR: 23.8; range: 1–45.7 months). Our series indicates that the anterior approach to the cervicothoracic junction and upper thoracic spine via partial sternotomy can be considered an effective option for treatment of anterior spinal pathologies, exhibiting a reasonable safety profile. Careful case selection is essential to adequately balance clinical benefits and surgical invasiveness for these procedures.

Published
2023
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24. Recommendations on the structure, personal, and organization of intensive care units

Author

Waydhas, Christian, Riessen, Reimer, Markewitz, Andreas, Hoffmann, Florian, Frey, Lorenz, Böttiger, Bernd W., Brenner, Sebastian, Brenner, Thorsten, Deffner, Teresa, Deininger, Matthias M., Janssens, Uwe, Kluge, Stefan, Marx, Gernot, Schwab, Stefan, Unterberg, Andreas W., Walcher, Felix, and van den Hooven, Thomas

Subjects
ddc:610
Abstract

Background: Intensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system. Objectives: To provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. Design and setting: Development of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force. Results: The recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied. Conclusion: This document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.

Published
2023

25. Computed Tomography Lesions and Their Association With Global Outcome in Young People With Mild Traumatic Brain Injury

Author

Lennart, Riemann, Ana, Mikolic, Andrew, Maas, Andreas W, Unterberg, Alexander, Younsi, Public Health, and Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI)

Subjects
Neurology (clinical), Human medicine
Abstract

Mild traumatic brain injury (mTBI) can be accompanied by structural damage to the brain. Here, we investigated how the presence of intracranial traumatic computed tomography (CT) pathologies relates to the global functional outcome in young patients one year after mTBI. All patients with mTBI (Glasgow Coma Scale: 13-15)

Published
2023

26. DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy

Author

M. E. Fenstermacher, J. Abbate, S. Abe, T. Abrams, M. Adams, B. Adamson, N. Aiba, T. Akiyama, P. Aleynikov, E. Allen, S. Allen, H. Anand, J. Anderson, Y. Andrew, T. Andrews, D. Appelt, R. Arbon, N. Ashikawa, A. Ashourvan, M. Aslin, Y. Asnis, M. Austin, D. Ayala, J. Bak, I. Bandyopadhyay, S. Banerjee, K. Barada, L. Bardoczi, J. Barr, E. Bass, D. Battaglia, A. Battey, W. Baumgartner, L. Baylor, J. Beckers, M. Beidler, E. Belli, J. Berkery, T. Bernard, N. Bertelli, M. Beurskens, R. Bielajew, S. Bilgili, B. Biswas, S. Blondel, J. Boedo, I. Bogatu, R. Boivin, T. Bolzonella, M. Bongard, X. Bonnin, P. Bonoli, M. Bonotto, A. Bortolon, S. Bose, N. Bosviel, S. Bouwmans, M. Boyer, W. Boyes, L. Bradley, R. Brambila, D. Brennan, S. Bringuier, L. Brodsky, M. Brookman, J. Brooks, D. Brower, G. Brown, W. Brown, M. Burke, K. Burrell, K. Butler, R. Buttery, I. Bykov, P. Byrne, A. Cacheris, K. Callahan, J. Callen, G. Campbell, J. Candy, J. Canik, P. Cano-Megias, N. Cao, L. Carayannopoulos, T. Carlstrom, W. Carrig, T. Carter, W. Cary, L. Casali, M. Cengher, G. Cespedes Paz, R. Chaban, V. Chan, B. Chapman, I. Char, A. Chattopadhyay, R. Chen, J. Chen, X. Chen, M. Chen, Z. Chen, M. Choi, W. Choi, G. Choi, L. Chousal, C. Chrobak, C. Chrystal, Y. Chung, R. Churchill, M. Cianciosa, J. Clark, M. Clement, S. Coda, A. Cole, C. Collins, W. Conlin, A. Cooper, J. Cordell, B. Coriton, T. Cote, J. Cothran, A. Creely, N. Crocker, C. Crowe, B. Crowley, T. Crowley, D. Cruz-Zabala, D. Cummings, M. Curie, D. Curreli, A. Dal Molin, B. Dannels, A. Dautt-Silva, K. Davda, G. De Tommasi, P. De Vries, G. Degrandchamp, J. Degrassie, D. Demers, S. Denk, S. Depasquale, E. Deshazer, A. Diallo, S. Diem, A. Dimits, R. Ding, S. Ding, W. Ding, T. Do, J. Doane, G. Dong, D. Donovan, J. Drake, W. Drews, J. Drobny, X. Du, H. Du, V. Duarte, D. Dudt, C. Dunn, J. Duran, A. Dvorak, F. Effenberg, N. Eidietis, D. Elder, D. Eldon, R. Ellis, W. Elwasif, D. Ennis, K. Erickson, D. Ernst, M. Fasciana, D. Fedorov, E. 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Verdoolaege, G., Vianello, N., Victor, B., Viezzer, E., Vincena, S., Wade, M., Waelbroeck, F., Wai, J., Wakatsuki, T., Walker, M., Wallace, G., Waltz, R., Wampler, W., Wang, L., Wang, H., Wang, Y., Wang, Z., Wang, G., Ward, S., Watkins, M., Watkins, J., Wehner, W., Wei, Y., Weiland, M., Weisberg, D., Welander, A., White, A., White, R., Wiesen, S., Wilcox, R., Wilks, T., Willensdorfer, M., Wilson, H., Wingen, A., Wolde, M., Wolff, M., Woller, K., Wolz, A., Wong, H., Woodruff, S., Wu, M., Wu, Y., Wukitch, S., Wurden, G., Xiao, W., Xie, R., Xing, Z., Xu, X., Xu, C., Xu, G., Yan, Z., Yang, X., Yang, S., Yokoyama, T., Yoneda, R., Yoshida, M., You, K., Younkin, T., Yu, J., Yu, M., Yu, G., Yuan, Q., Zaidenberg, L., Zakharov, L., Zamengo, A., Zamperini, S., Zarnstorff, M., Zeger, E., Zeller, K., Zeng, L., Zerbini, M., Zhang, L., Zhang, X., Zhang, R., Zhang, B., Zhang, J., Zhao, L., Zhao, B., Zheng, Y., Zheng, L., Zhu, B., Zhu, J., Zhu, Y., Zsutty, M., Zuin, M., Fenstermacher, M, Abbate, J, 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S, Kulchar, J, Kwon, K, La Haye, R, Laggner, F, Lan, H, Lantsov, R, Lao, L, Esquisabel, A, Lasnier, C, Lau, C, Leard, B, Lee, J, Lee, R, Lee, M, Lee, Y, Lee, C, Lee, S, Lehnen, M, Leonard, A, Leppink, E, Lesher, M, Lestz, J, Leuer, J, Leuthold, N, Li, X, Li, K, Li, E, Li, G, Li, L, Li, Z, Li, J, Li, Y, Lin, Z, Lin, D, Liu, X, Liu, J, Liu, Y, Liu, T, Liu, C, Liu, Z, Liu, D, Liu, A, Loarte-Prieto, A, Lodestro, L, Logan, N, Lohr, J, Lombardo, B, Lore, J, Luan, Q, Luce, T, Di Cortemiglia, T, Luhmann, N, Lunsford, R, Luo, Z, Lvovskiy, A, Lyons, B, Ma, X, Madruga, M, Madsen, B, Maggi, C, Maheshwari, K, Mail, A, Mailloux, J, Maingi, R, Major, M, Makowski, M, Manchanda, R, Marini, C, Marinoni, A, Maris, A, Markovic, T, Marrelli, L, Martin, E, Mateja, J, Matsunaga, G, Maurizio, R, Mauzey, P, Mauzey, D, Mcardle, G, Mcclenaghan, J, Mccollam, K, Mcdevitt, C, Mckay, K, Mckee, G, Mclean, A, Mehta, V, Meier, E, Menard, J, Meneghini, O, Merlo, G, Messer, S, Meyer, W, Michael, C, Michoski, C, Milne, P, Minet, G, Misleh, A, Mitrishkin, Y, Moeller, C, Montes, K, Morales, M, Mordijck, S, Moreau, D, Morosohk, S, Morris, P, Morton, L, Moser, A, Moyer, R, Moynihan, C, Mrazkova, T, Mueller, D, Munaretto, S, Burgos, J, Murphy, C, Murphy, K, Muscatello, C, Myers, C, Nagy, A, Nandipati, G, Navarro, M, Nave, F, Navratil, G, Nazikian, R, Neff, A, Neilson, G, Neiser, T, Neiswanger, W, Nelson, D, Nelson, A, Nespoli, F, Nguyen, R, Nguyen, L, Nguyen, X, Nichols, J, Nocente, M, Nogami, S, Noraky, S, Norausky, N, Nornberg, M, Nygren, R, Odstrcil, T, Ogas, D, Ogorman, T, Ohdachi, S, Ohtani, Y, Okabayashi, M, Okamoto, M, Olavson, L, Olofsson, E, Omullane, M, Oneill, R, Orlov, D, Orvis, W, Osborne, T, Pace, D, Canal, G, Martinez, A, Palacios, L, Pan, C, Pan, Q, Pandit, R, Pandya, M, Pankin, A, Park, Y, Park, J, Parker, S, Parks, P, Parsons, M, Patel, B, Pawley, C, Paz-Soldan, C, Peebles, W, Pelton, S, Perillo, R, Petty, C, Peysson, Y, Pierce, D, Pigarov, A, Pigatto, L, Piglowski, D, Pinches, S, Pinsker, R, Piovesan, P, Piper, N, Pironti, A, Pitts, R, Pizzo, J, Plank, U, Podesta, M, Poli, E, Poli, F, Ponce, D, Popovic, Z, Porkolab, M, Porter, G, Powers, C, Powers, S, Prater, R, Pratt, Q, Pusztai, I, Qian, J, Qin, X, Ra, O, Rafiq, T, Raines, T, Raman, R, Rauch, J, Raymond, A, Rea, C, Reich, M, Reiman, A, Reinhold, S, Reinke, M, Reksoatmodjo, R, Ren, Q, Ren, Y, Ren, J, Rensink, M, Renteria, J, Rhodes, T, Rice, J, Roberts, R, Robinson, J, Fernandez, P, Rognlien, T, Rosenthal, A, Rosiello, S, Rost, J, Roveto, J, Rowan, W, Rozenblat, R, Ruane, J, Rudakov, D, Ruiz, J, Rupani, R, Saarelma, S, Sabbagh, S, Sachdev, J, Saenz, J, Saib, S, Salewski, M, Salmi, A, Sammuli, B, Samuell, C, Sandorfi, A, Sang, C, Sarff, J, Sauter, O, Schaubel, K, Schmitz, L, Schmitz, O, Schneider, J, Schroeder, P, Schultz, K, Schuster, E, Schwartz, J, Sciortino, F, Scotti, F, Scoville, J, Seltzman, A, Seol, S, Sfiligoi, I, Shafer, M, Sharapov, S, Shen, H, Sheng, Z, Shepard, T, Shi, S, Shibata, Y, Shin, G, Shiraki, D, Shousha, R, Si, H, Simmerling, P, Sinclair, G, Sinha, J, Sinha, P, Sips, G, Sizyuk, T, Skinner, C, Sladkomedova, A, Slendebroek, T, Slief, J, Smirnov, R, Smith, J, Smith, S, Smith, D, Snipes, J, Snoep, G, Snyder, A, Snyder, P, Solano, E, Solomon, W, Song, J, Sontag, A, Soukhanovskii, V, Spendlove, J, Spong, D, Squire, J, Srinivasan, C, Stacey, W, Staebler, G, Stagner, L, Stange, T, Stangeby, P, Stefan, R, Stemprok, R, Stephan, D, Stillerman, J, Stoltzfus-Dueck, T, Stonecipher, W, Storment, S, Strait, E, Su, D, Sugiyama, L, Sun, Y, Sun, P, Sun, Z, Sun, A, Sundstrom, D, Sung, C, Sungcoco, J, Suttrop, W, Suzuki, Y, Suzuki, T, Svyatkovskiy, A, Swee, C, Sweeney, R, Sweetnam, C, Szepesi, G, Takechi, M, Tala, T, Tanaka, K, Tang, X, Tang, S, Tao, Y, Tao, R, Taussig, D, Taylor, T, Teixeira, K, Teo, K, Theodorsen, A, Thomas, D, Thome, K, Thorman, A, Thornton, A, Ti, A, Tillack, M, Timchenko, N, Tinguely, R, Tompkins, R, Tooker, J, De Sousa, A, Trevisan, G, Tripathi, S, Ochoa, A, Truong, D, Tsui, C, Turco, F, Turnbull, A, Umansky, M, Unterberg, E, Vaezi, P, Vail, P, Valdez, J, Valkis, W, Van Compernolle, B, Van Galen, J, Van Kampen, R, Van Zeeland, M, Verdoolaege, G, Vianello, N, Victor, B, Viezzer, E, Vincena, S, Wade, M, Waelbroeck, F, Wai, J, Wakatsuki, T, Walker, M, Wallace, G, Waltz, R, Wampler, W, Wang, L, Wang, H, Wang, Y, Wang, Z, Wang, G, Ward, S, Watkins, M, Watkins, J, Wehner, W, Wei, Y, Weiland, M, Weisberg, D, Welander, A, White, A, White, R, Wiesen, S, Wilcox, R, Wilks, T, Willensdorfer, M, Wilson, H, Wingen, A, Wolde, M, Wolff, M, Woller, K, Wolz, A, Wong, H, Woodruff, S, Wu, M, Wu, Y, Wukitch, S, Wurden, G, Xiao, W, Xie, R, Xing, Z, Xu, X, Xu, C, Xu, G, Yan, Z, Yang, X, Yang, S, Yokoyama, T, Yoneda, R, Yoshida, M, You, K, Younkin, T, Yu, J, Yu, M, Yu, G, Yuan, Q, Zaidenberg, L, Zakharov, L, Zamengo, A, Zamperini, S, Zarnstorff, M, Zeger, E, Zeller, K, Zeng, L, Zerbini, M, Zhang, L, Zhang, X, Zhang, R, Zhang, B, Zhang, J, Zhao, L, Zhao, B, Zheng, Y, Zheng, L, Zhu, B, Zhu, J, Zhu, Y, Zsutty, M, Zuin, M, Lawrence Livermore National Laboratory, Princeton Plasma Physics Laboratory, Princeton University, General Atomics, Max-Planck-Institut für Plasmaphysik, Imperial College London, National Institute for Fusion Science, Universidade de São Paulo, University of Texas at Austin, ITER, College of William and Mary, University of California Los Angeles, University of California San Diego, Columbia University, Massachusetts Institute of Technology, Oak Ridge National Laboratory, Eindhoven University of Technology, Oak Ridge Associated Universities, West Virginia University, University of Tennessee, Knoxville, National Research Council of Italy, Stony Brook University, Purdue University, University of Seville, University of Science and Technology of China, Carnegie Mellon University, Institute for Plasma Research, Peking University, University of California Davis, University of California Irvine, Commonwealth Fusion Systems, University of Liverpool, University of Illinois at Urbana-Champaign, University of Milan - Bicocca, Georgia Institute of Technology, Southwestern Institute of Physics, University of Toronto, Auburn University, Polytechnic University of Turin, Universidade Lisboa, Association CCFE, KTH Royal Institute of Technology, San Diego State University, Durham University, Lehigh University, Fusion and Plasma Physics, University of Washington, Department of Applied Physics, Sandia National Laboratories, Ghent University, Technical University of Denmark, CEA, University of Colorado Boulder, Harvard University, National Technical University of Athens, Coventry University, University of Stuttgart, Czech Academy of Sciences, Harvey Mudd College, Seoul National University, Donghua University, University of York, Dalian University of Technology, University of California Berkeley, Los Alamos National Laboratory, United States Department of Energy, University of British Columbia, Pacific Northwest National Laboratory, University of Wisconsin, Michigan State University, University of Strathclyde, Pennsylvania State University, Rensselaer Polytechnic Institute, University of Southern California, Chalmers University of Technology, University of Virginia, University of Naples Federico II, University of Oxford, VTT Technical Research Centre of Finland, National Institute of Technology, University of Connecticut, DIFFER, CIEMAT, Hanyang University, Brigham Young University, UiT The Arctic University of Norway, Australian National University, Russian Research Centre Kurchatov Institute, Forschungszentrum Jülich, Zhejiang University, The University of Tokyo, University of Michigan, Agenzia nazionale per le nuove tecnologie, l'energia e lo sviluppo economico sostenibile, Aalto-yliopisto, Aalto University, DIII-D Team, Complex Ionized Media, Elementary Processes in Gas Discharges, Applied Physics and Science Education, Science and Technology of Nuclear Fusion, and Control Systems Technology

Subjects
Nuclear and High Energy Physics, Tokamak, Technology and Engineering, DIII-D, Nuclear engineering, TOKAMAKS, MITIGATION, law.invention, Plasma physics, mitigation, law, plasma physic, tokamak, Physics, Core-edge integration, Basis (linear algebra), plasma physics, core-edge integration, scenarios, Fusion power, Condensed Matter Physics, SCENARIOS, fusion energy, Fusion energy
Abstract

Funding Information: This material is based upon work supported by the US Department of Energy, Office of Science, Office of Fusion Energy Sciences, using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-FC02-04ER54698 and DE-AC52-07NA27344. Publisher Copyright: © 2022 IAEA, Vienna. DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.

Published
2022
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27. The value of intraoperative MRI for resection of functional pituitary adenomas—a critical assessment of a consecutive single-center series of 114 cases

Author

Moritz Scherer, Paul Zerweck, Daniela Becker, Lars Kihm, Jessica Jesser, Christopher Beynon, and Andreas Unterberg

Subjects
Adenoma, Treatment Outcome, Acromegaly, Humans, Pituitary Neoplasms, Surgery, Neurology (clinical), General Medicine, Cushing Syndrome, Magnetic Resonance Imaging, Hormones, Retrospective Studies
Abstract

This series sought to evaluate the role of intraoperative MRI (iMRI) for resection of functional pituitary adenomas (FPAs). We retrospectively reviewed clinical data of 114 consecutive FPAs with excessive hormone secretion treated with transsphenoidal surgery and iMRI during 01/2010–12/2017. We focused on iMRI findings, extend of resection and postoperative hormonal remission. Variables of incomplete resections and persistent hormone excess were evaluated by binary regression. Patients with FPAs presented with hypercortisolism (n = 23, 20%), acromegaly (n = 56, 49%), and as prolactinomas (n = 35, 31%) resistant to medical treatment. Preoperative MRI showed 81 macroadenomas (71%) and optic system involvement in 41 cases (36%). IMRI was suggestive for residual tumor in 51 cases (45%). Re-inspection of the cavity cleared equivocal findings in 16 cases (14%). Additional tumor was removed in 22 cases (19%). Complete resection was achieved in 95 cases (83%). Postoperative morbidity was low (1.7% revision surgeries, 0.8% permanent diabetes insipidus). Overall hormonal remission-rate was 59% (hypercortisolism 78%, acromegaly 52%, prolactinoma 57%). Supra- and parasellar invasion and preoperative visual impairment were significant predictors for incomplete resections despite use of iMRI. Risk for persistent hormone excess was increased sevenfold after incomplete resections. IMRI enabled reliable identification of tumor remnants during surgery and triggered further resection in a considerable proportion of cases. Nevertheless, tumor size and invasiveness set persistent boundaries to the completeness of resections. The low rate of surgical complications could point at a less invasive iMRI-guided surgical approach while achieving a complete tumor resection was a crucial determinant for hormonal outcome.

Published
2022
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28. Rapid-CNS2: rapid comprehensive adaptive nanopore-sequencing of CNS tumors, a proof-of-concept study

Author

Areeba Patel, Helin Dogan, Alexander Payne, Elena Krause, Philipp Sievers, Natalie Schoebe, Daniel Schrimpf, Christina Blume, Damian Stichel, Nadine Holmes, Philipp Euskirchen, Jürgen Hench, Stephan Frank, Violaine Rosenstiel-Goidts, Miriam Ratliff, Nima Etminan, Andreas Unterberg, Christoph Dieterich, Christel Herold-Mende, Stefan M. Pfister, Wolfgang Wick, Matthew Loose, Andreas von Deimling, Martin Sill, David T. W. Jones, Matthias Schlesner, and Felix Sahm

Subjects
Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine
Published
2022
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29. Analysis of recurrence probability following radiotherapy in patients with CNS WHO grade 2 meningioma using integrated molecular-morphologic classification

Author

Maximilian Y Deng, Felix Hinz, Sybren L N Maas, Günes Anil, Philipp Sievers, Cristina Conde-Lopez, Jonathan Lischalk, Sophie Rauh, Tanja Eichkorn, Sebastian Regnery, Lukas Bauer, Thomas Held, Eva Meixner, Kristin Lang, Juliane Hörner-Rieber, Klaus Herfarth, David Jones, Stefan M Pfister, Christine Jungk, Andreas Unterberg, Wolfgang Wick, Andreas von Deimling, Jürgen Debus, Felix Sahm, and Laila König

Subjects
Oncology, Surgery, Neurology (clinical)
Abstract

Background The current CNS WHO classification of brain tumors distinguishes three malignancy grades in meningiomas, with increasing risk of recurrence from CNS WHO grade 1 to 3. Radiotherapy is recommended by current EANO guidelines for patients not safely amenable to surgery or after incomplete resection in higher grades. Despite adequately predicting recurrence probability for the majority of CNS WHO grade 2 meningioma patients, a considerable subset of patients demonstrates an unexpectedly early tumor recurrence following radiotherapy. Methods A retrospective cohort of 44 patients with CNS WHO grade 2 meningiomas was stratified into 3 risk groups (low, intermediate, high) using an integrated morphological, CNV- and methylation family-based classification. Local progression-free survival (lPFS) following radiotherapy (RT) was analyzed and total dose of radiation was correlated with survival outcome. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities were further assessed. Results Risk stratification of CNS WHO grade 2 meningioma into integrated risk groups demonstrated a significant difference in 3-year lPFS following radiotherapy between the molecular low- and high-risk group. Recurrence pattern analysis revealed that 87.5 % of initial relapses occurred within the RT planning target volume or resection cavity. Conclusion Integrated risk scoring can identify CNS WHO grade 2 meningioma patients at risk or relapse and dissemination following radiotherapy. Therapeutic management of CNS WHO grade 2 meningiomas and future clinical trials should be adjusted according to the molecular risk-groups, and not rely on conventional CNS WHO grading alone.

Published
2023
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30. Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model

Author

Guoli Zheng, Anna-Kathrin Harms, Mohamed Tail, Hao Zhang, Alan Nimmo, Thomas Skutella, Karl Kiening, Andreas Unterberg, Klaus Zweckberger, and Alexander Younsi

Subjects
Cellular and Molecular Neuroscience, Molecular Biology
Abstract

ObjectiveDisruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model.MethodsFemale Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet & dry weight and immunohistological analyses were conducted.ResultsSubstance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters.ConclusionIntrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery.

Published
2023
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31. Data-driven indirect punch wear monitoring in sheet-metal stamping processes

Author

Martin Unterberg, Marco Becker, Philipp Niemietz, and Thomas Bergs

Subjects
Artificial Intelligence, Industrial and Manufacturing Engineering, Software
Abstract

The wear state of the punch in sheet-metal stamping processes cannot be directly observed, necessitating the use of indirect methods to infer its condition. Past research approaches utilized a plethora of machine learning models to infer the punch wear state from suitable process signals, but have been limited by the lack of industrial-grade process setups and sample sizes as well as their insufficient interpretability. This work seeks to address these limitations by proposing the sheared surface of the scrap web as a proxy for the punch wear and modeling its quality from acoustic emission signals. The experimental work was carried out in an industrial-grade fine blanking process setting. Evaluation of the model performances suggests that the utilized regression models are capable of modeling the relationship between acoustic emission signal features and sheared surface quality of the scrap webs. Subsequent model inference suggests adhesive wear on the punch as a root cause for the sheared surface impairment of the scrap webs. This work represents the most extensive modeling effort on indirect punch wear monitoring in sheet-metal stamping both from a model prediction and model inference perspective known to the authors.

Published
2023
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32. HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma

Author

Marius Felix, Dennis Friedel, Ashok Kumar Jayavelu, Katharina Filipski, Annekathrin Reinhardt, Uwe Warnken, Damian Stichel, Daniel Schrimpf, Andrey Korshunov, Yueting Wang, Tobias Kessler, Nima Etminan, Andreas Unterberg, Christel Herold-Mende, Laura Heikaus, Felix Sahm, Wolfgang Wick, Patrick N Harter, Andreas von Deimling, and David E Reuss

Subjects
Proteomics, Cancer Research, Brain Neoplasms, Oligodendroglioma, Microfilament Proteins, Glioma, Astrocytoma, Immunohistochemistry, Isocitrate Dehydrogenase, Oncology, Chromosomes, Human, Pair 1, Mutation, Basic and Translational Investigations, Humans, Vimentin, Neurology (clinical), Chromosomes, Human, Pair 19, Adaptor Proteins, Signal Transducing
Abstract

Background IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression. Methods Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant). Results We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%. Conclusions We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.

Published
2023

34. DIVI-Empfehlung zur Struktur und Ausstattung von Intensivstationen 2022 (Erwachsene)

Author

Christian Waydhas, Reimer Riessen, Andreas Markewitz, Florian Hoffmann, Lorenz Frey, Bernd W. Böttiger, Sebastian Brenner, Thorsten Brenner, Teresa Deffner, Matthias Manfred Deininger, Uwe Janssens, Stefan Kluge, Gernot Marx, Stefan Schwab, Andreas Unterberg, Felix Walcher, and Thomas van den Hooven

Subjects
Emergency Medicine, Internal Medicine, Emergency Nursing, Critical Care and Intensive Care Medicine
Published
2023
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35. Mortality, complication risks, and clinical outcomes after surgical treatment of spinal epidural abscess: a comparative analysis of patients aged 18–64 years, 65–79 years, and ≥ 80 years, with a 3-year follow-up

Author

Pavlina Lenga, Gelo Gülec, Karl Kiening, Andreas W. Unterberg, and Basem Ishak

Subjects
Surgery, Neurology (clinical), General Medicine
Abstract

Spinal epidural abscess (SEA) with pyogenic vertebral osteomyelitis (PVO) is a rare illness with a steadily increasing incidence. However, comparative analyses of young and older patients with SEA are lacking. We aimed to compare the clinical course of patients aged 18–64 years, 65–79 years, and ≥ 80 years undergoing surgery for SEA. Clinical and imaging data were retrospectively collected from the institutional database between September 2005 and December 2021. Ninety-nine patients aged 18–64 years, 45 patients aged 65–79 years, and 32 patients ≥ 80 years were enrolled. Patients ≥ 80 years presented with a poorer baseline history (9.2 ± 2.4), as indicated by the CCI, than their younger counterparts (18–74 years: 4.8 ± 1.6;6.5 ± 2.5; p 65 years), presence of comorbidities, and poor preoperative neurological condition were significant predictors of mortality. Surgical management led to significant improvements in laboratory and clinical parameters in all age groups. However, older patients are prone to multiple risks, requiring meticulous evaluation before surgery. Nevertheless, the risk profile of younger patients should not be underestimated. The study has the limitations of a retrospective design and small sample size. Larger randomized studies are warranted to establish the guidelines for the optimal management of patients from every age group and to identify the patients who can benefit from solely conservative management.

Published
2023
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36. The effectiveness of D2 pellet injection in reducing intra-ELM and inter-ELM tungsten divertor erosion rates in DIII-D during the Metal Rings Campaign

Author

Alec Cacheris, Tyler Abrams, Larry R Baylor, Daisuke Shiraki, Ezekial Unterberg, and David Donovan

Subjects
Nuclear Energy and Engineering, Condensed Matter Physics
Abstract

Edge localized modes (ELMs) in H-mode plasmas erode plasma-facing components (PFCs) and lead to impurities in the core, reducing confinement. This study analyzes D2 pellet injection on the DIII-D fusion experiment used as an ELM mitigation technique applied during the 2016 tungsten Metal Rings Campaign (MRC) [1] to reduce W erosion during ELMs. WI filterscope channels and Langmuir probes were used to infer the gross erosion rate of tungsten-coated tiles installed in the divertor of DIII-D [2]. D2 mass injection rates ranging from 34-41 A.U. and no D2 injection resulted in a similar total W erosion rate during ELMs (intra-ELM). On average, results show a 29% increase in the total gross W erosion rate with intermediate mass injection rates (~13-23 A.U.) compared to the no pellets and the highest injection rate cases. On average, the fast D2 mass injection rate cases had 15% less erosion in the inter-ELM phase than the case with no pellets. Generally, higher D2 mass injection rates increased the ELM frequency, and the highest injection rates reduced the average erosion per ELM and fractional carbon impurities at the top of the pedestal by nearly 40% when compared to the no-pellet case. As expected, a higher D2 pellet injection rate led to a higher plasma density and lower plasma temperature in the divertor. Additionally, an increasing divertor inter-ELM plasma electron density directly correlated to more frequent pellet injection and a decrease in both the average gross intra-ELM W erosion and the total gross intra-ELM W erosion rate. Simulations of intra-ELM erosion using the ‘free-streaming plus recycling model’ (FSRM) [2] underestimate W erosion during pellet injection by about 30% on average. The discrepancies between the experimental measurements and the FSRM intra-ELM W erosion predictions are postulated to be due to C/W material mixing. A simple analytic mixed-material model is presented and results in better agreement with the experimental data. These results highlight the importance of incorporating the effects of a mixed-material layer in the analysis of PFC erosion.

Published
2023
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38. Data from Pharmacological Landscape of FDA-Approved Anticancer Drugs Reveals Sensitivities to Ixabepilone, Romidepsin, Omacetaxine, and Carfilzomib in Aggressive Meningiomas

Author

Christel Herold-Mende, Andreas Unterberg, Rolf Warta, Amir Abdollahi, Mahmoud Moustafa, Montadar Alaa Eddine, Junguo Cao, Fang Liu, Tao Yu, and Gerhard Jungwirth

Abstract

Purpose:To date, there are no systemic treatment options for patients with recurrent or refractory meningioma.Experimental Design:To identify effective drugs, we performed a large-scale drug screening using FDA-approved drugs on several meningioma cell lines. The impact of the top four compounds was assessed on cell viability, proliferation, colony formation, migration, and apoptosis. In addition, the antineoplastic effects of the selected drugs were validated in a heterotopic xenograft mouse model.Results:Analyses of the viability of meningioma cells treated with 119 antineoplastic FDA-approved drugs resulted in categorization into sensitive and resistant drug–response groups based on the mean IC50 values and peak serum concentrations (Cmax) in patients. Eighty drugs, including 15 alkylating agents, 14 antimetabolites, and 13 tyrosine kinase inhibitors, were classified as resistant (IC50 > Cmax). The sensitive drug–response group (n = 29, IC50 < Cmax) included RNA/protein synthesis inhibitors, proteasome inhibitors, topoisomerase, tyrosine-kinase, and partial histone deacetylase and microtubule inhibitors. The IC50 value of the four most effective compounds (carfilzomib, omacetaxine, ixabepilone, and romidepsin) ranged from 0.12 to 9.5 nmol/L. Most of them caused cell-cycle arrest in the G2–M-phase and induced apoptosis. Furthermore, all drugs except romidepsin significantly inhibited tumor growth in vivo. The strongest antineoplastic effect was observed for ixabepilone, which reduced tumor volume by 86%.Conclusions:In summary, a large-scale drug screening provides a comprehensive insight into the anti-meningioma activities of FDA-approved drugs, and identified carfilzomib, omacetaxine, ixabepilone, and romidepsin as novel potent antineoplastic agents for the treatment of aggressive meningiomas. The most pronounced effects were observed with ixabepilone mandating for further clinical investigation.

Published
2023
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42. Data from Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Thomas Korff, Rupert C. Ecker, Volker Eckstein, Nobuyoshi Hiraoka, Stefan Grau, Rezvan Ahmadi, Christine Dictus, Yingzi Ge, Andrea Huppertz, Thomas Ratliff, and Jennifer Lohr

Abstract

Purpose: In glioma—in contrast to various other cancers—the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma.Experimental Design: T-cell subpopulations from entire sections of 93 WHO°II–IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO°II–IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells.Results: Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (Teff, cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of Teff cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-β molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-β receptor signaling increased transmigration.Conclusions: This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-β1 and TGF-β2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches. Clin Cancer Res; 17(13); 4296–308. ©2011 AACR.

Published
2023
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43. Suppl. Figure 7 from Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Markus A. Weigand, Christoph Schramm, Niels Grabe, Volker Eckstein, Uwe Warnken, Christine Jungk, Saskia Roesch, Kolja Pocha, David Reuss, Anchana Rathinasamy, Carmen Rapp, Martina Schnölzer, Rolf Warta, Slava Stamova, and Steffen Dettling

Abstract

Representative multicolor stainings of CFL1, CRKII, NME2, and CNTN1 on acetone-fixed cryosections with markers for common cell types in IDHmut LGGs: anti-GFAP (tumor cells, #Z0334, DAKO), anti-CD68 (microglia/ macrophages, #M0718, DAKO), anti-CD31 (endothelial cells, #223609, BD Pharmingen). Detection was performed by using fluorochrom-conjugated secondary antibodies (anti-mouse AF647 (#A-21463, Invitrogen), anti-rabbit AF555 (#A-21428, Invitrogen), DAPI (#D1306, ThermoFisher), and the Zenon AF488 mouse IgG1 Labeling Kit (#Z25001, ThermoFisher)) according to the manufacturer`s protocol (scale bar: 50 µM, scale bar zoom: 10 µM).

Published
2023
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44. Supplementary Data from Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

Author

Bernhard Radlwimmer, Christel Herold-Mende, Peter Lichter, Guido Reifenberger, Andreas Unterberg, Anna Starzinski-Powitz, Benito Campos, Sebastian Barbus, Jochen Hess, Moritz Durchdewald, Heike Peterziel, Michael Sabel, Jörg Felsberg, Christian Hartmann, Felix Engel, Andrey Korshunov, Natalia Becker, Rezvan Ahmadi, Stefanie Hofmann, and Aurélie Ernst

Abstract

Supplementary Data from Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

Published
2023
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45. Supplementary Figures 1-5 from Cytotoxic T Cells and their Activation Status are Independent Prognostic Markers in Meningiomas

Author

Christel C. Herold-Mende, Matthias Simon, Andreas Unterberg, Andreas von Deimling, Juergen Debus, Amir Abdollahi, Manfred Westphal, Christian Senft, Steffi Urbschat, Ralf Ketter, Mario Loehr, Niels Grabe, Almuth F. Kessler, Konstaninos Gousias, Katrin Lamszus, Klaus Zweckberger, Gerhard Jungwirth, Melissa Schmidt, Felix Sahm, Andreas Mock, Saskia Roesch, Christine Jungk, Rolf Warta, Anna Theresa Ull, Fang Liu, Steffen Dettling, and Carmen Rapp

Abstract

Fig. S1: Workflow; Fig. S2: Representative gating strategy for TissueFAXS analysis; Fig. S3: Analysis of helper, cytotoxic and regulatory T cell infiltration and the proportion of PD-1-expressing T cells; Fig. S4: Association between the infiltration of T cells and survival; Fig. S5: Levels of tumor-infiltrating T lymphocytes (TILs) in meningiomas, separated by their localization.

Published
2023
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46. Suppl. Figure 5 from Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Markus A. Weigand, Christoph Schramm, Niels Grabe, Volker Eckstein, Uwe Warnken, Christine Jungk, Saskia Roesch, Kolja Pocha, David Reuss, Anchana Rathinasamy, Carmen Rapp, Martina Schnölzer, Rolf Warta, Slava Stamova, and Steffen Dettling

Abstract

Representative images of immunohistochemical stainings of the isotype controls IgG and IgG1 in normal brain (NB) tissues, astrocytomas (WHO{degree sign}II: n = 10; WHO{degree sign}III: n = 10), and oligodendrogliomas (WHO{degree sign}II: n = 10; WHO{degree sign}III: n = 10). Scale bar: 50 µm.

Published
2023
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47. Supplementary Data from Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Thomas Korff, Rupert C. Ecker, Volker Eckstein, Nobuyoshi Hiraoka, Stefan Grau, Rezvan Ahmadi, Christine Dictus, Yingzi Ge, Andrea Huppertz, Thomas Ratliff, and Jennifer Lohr

Abstract

Supplementary Figures S1-S1-; Supplementary Tables S1-S2.

Published
2023
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48. Figure S1 from Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival

Author

Christel C. Herold-Mende, Andreas Unterberg, Amir Abdollahi, Andreas von Deimling, Juergen Debus, David Reuss, Niels Grabe, Leila R. Martins, Christine Jungk, Christoph Geisenberger, Rolf Warta, Steffen Dettling, Carmen Rapp, Andreas Mock, and Kolja Pocha

Abstract

TissueQuest gating strategy and Kaplan-Meier plots of significant clinical parameters.

Published
2023
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49. Suppl. Figure 9 from Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Markus A. Weigand, Christoph Schramm, Niels Grabe, Volker Eckstein, Uwe Warnken, Christine Jungk, Saskia Roesch, Kolja Pocha, David Reuss, Anchana Rathinasamy, Carmen Rapp, Martina Schnölzer, Rolf Warta, Slava Stamova, and Steffen Dettling

Abstract

(A) IFN-� ELISpot raw data of all HLA-A*02:01 patients analyzed (n = 7) showing the IFN-� spots / 1x105 T-cells for patient cells against TAAs vs. patient cells against the negative control (human immunodeficiency virus (HIV) gag/pol, 9 amino acids). Grey bars indicate a significantly increased immunogenicity compared to negative control (solid line). (B) Homogenous levels of stimulation while comparing the total immune response by mean of IFN-� spot numbers among astrocytomas (red) and oligodendrogliomas (blue) to a certain reactive epitope. (n.s., not significant, *, p < 0.05; **, p < 0.01)

Published
2023
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50. Suppl. Figure 2 from Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma

Author

Christel Herold-Mende, Philipp Beckhove, Andreas Unterberg, Andreas von Deimling, Markus A. Weigand, Christoph Schramm, Niels Grabe, Volker Eckstein, Uwe Warnken, Christine Jungk, Saskia Roesch, Kolja Pocha, David Reuss, Anchana Rathinasamy, Carmen Rapp, Martina Schnölzer, Rolf Warta, Slava Stamova, and Steffen Dettling

Abstract

IFN-� ELISpot raw data to validate antigen immunogenicity in patients of origin. Antigens with a significant increased immunogenicity (grey bars and asterisks) or 1.3-fold increased levels of immune responses (grey bars) were further validated in a bigger study sample of healthy individuals and lower-grade glioma patients. Solid line represents mean background of negative control (IgG1). (*, p < 0.05; **, p < 0.01; ***, p < 0.001)

Published
2023
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