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1. Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions

Author

Daniel Butler, Christopher Mozsary, Cem Meydan, Jonathan Foox, Joel Rosiene, Alon Shaiber, David Danko, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Evan T. Sholle, Edward J. Schenck, Craig D. Westover, Ciaran Hassan, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Dianna L. Ng, Andrea C. Granados, Yale A. Santos, Venice Servellita, Scot Federman, Phyllis Ruggiero, Arkarachai Fungtammasan, Chen-Shan Chin, Nathaniel M. Pearson, Bradley W. Langhorst, Nathan A. Tanner, Youngmi Kim, Jason W. Reeves, Tyler D. Hether, Sarah E. Warren, Michael Bailey, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Mara Couto-Rodriguez, Dorottya Nagy-Szakal, Joseph Barrows, Heather Wells, Niamh B. O’Hara, Jeffrey A. Rosenfeld, Ying Chen, Peter A. D. Steel, Amos J. Shemesh, Jenny Xiang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Angelika Iftner, Daniela Bezdan, Elizabeth Sanchez, Thomas R. Campion, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Sagi Shapira, Iman Hajirasouliha, Alain Borczuk, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa Cushing, Shixiu Wu, Shawn Levy, Charles Chiu, Robert E. Schwartz, Nicholas Tatonetti, Hanna Rennert, Marcin Imielinski, and Christopher E. Mason

Subjects
Science
Abstract

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

Published
2021
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2. Genomic and immunologic correlates of LAG-3 expression in cancer

Author

Anshuman Panda, Jeffrey A. Rosenfeld, Eric A. Singer, Gyan Bhanot, and Shridar Ganesan

Subjects
immune checkpoint blockade, lag-3, mutation burden, virus, endogenous retrovirus, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Immune checkpoint blockade leads to unprecedented responses in many cancers. Although currently available agents mostly target the PD-1 and CTLA-4 pathways, agents targeting the immune checkpoint protein LAG-3 are under active clinical development, and early clinical data show that LAG-3 expression is a biomarker of response to LAG-3 blockade. To determine which cancers may benefit most from LAG-3 blockade, we performed a pan-cancer analysis of The Cancer Genome Atlas dataset to identify genomic and immunologic correlates of LAG-3 expression. High mutation burden, and expression of exogenous virus (EBV, HPV) or endogenous retrovirus (ERV3-2), were associated with overexpression of LAG-3 in multiple cancers. Although CD8+ T-cell marker (CD8A) and LAG-3 were strongly co-expressed with each other and with PD-L1 in most cancers, there were three notable exceptions: HPV+ head-neck squamous cell cancer, renal cell cancer, and glioblastoma. These results may have important implications for guiding development clinical trials of LAG-3 blockade.

Published
2020
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3. Genome assembly and geospatial phylogenomics of the bed bug Cimex lectularius

Author

Jeffrey A. Rosenfeld, Darryl Reeves, Mercer R. Brugler, Apurva Narechania, Sabrina Simon, Russell Durrett, Jonathan Foox, Kevin Shianna, Michael C. Schatz, Jorge Gandara, Ebrahim Afshinnekoo, Ernest T. Lam, Alex R. Hastie, Saki Chan, Han Cao, Michael Saghbini, Alex Kentsis, Paul J. Planet, Vladyslav Kholodovych, Michael Tessler, Richard Baker, Rob DeSalle, Louis N. Sorkin, Sergios-Orestis Kolokotronis, Mark E. Siddall, George Amato, and Christopher E. Mason

Subjects
Science
Abstract

The common bedbug is a pest for humans, yet its molecular biology is poorly understood. Here, the authors sequence the common bedbug genome and profile gene expression across all life stages to show major changes in gene expression after feeding on human blood.

Published
2016
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4. Rationale and Methods for Updated Guidelines for the Management of Penetrating Traumatic Brain Injury

Author

Gregory W.J. Hawryluk, Shelley Selph, Angela Lumba-Brown, Annette M. Totten, Jamshid Ghajar, Bizhan Aarabi, James Ecklund, Stacy Shackelford, Britton Adams, David Adelson, Rocco A. Armonda, John Benjamin, Darrell Boone, David Brody, Bradley Dengler, Anthony Figaji, Gerald Grant, Odette Harris, Alan Hoffer, Ryan Kitigawa, Kerry Latham, Christopher Neal, David O. Okonkwo, Dylan Pannell, Jeffrey V. Rosenfeld, Guy Rosenthal, Andres Rubiano, Deborah M. Stein, Martina Stippler, Max Talbot, Alex Valadka, David W. Wright, Shelton Davis, and Randy Bell

Subjects
blast injury, guidelines, head trauma, penetrating brain injury, traumatic brain injury, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings.

Published
2022
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6. The Impact of Major Military War Campaigns on Neurosurgery: Informetric Data and Time-Trend Analysis

Author

Sulaman Durrani, Karim Rizwan Nathani, William Mualem, Ali Shoushtari, Juliana Rotter, Jeffrey V. Rosenfeld, and Mohamad Bydon

Subjects
Military Personnel, World War II, Neurosurgery, Humans, Surgery, Neurology (clinical), Military Medicine, Iraq War, 2003-2011, United States
Abstract

Given the neurotrauma that soldiers might face during wars, a byproduct of such devastating neurosurgical conditions can be novel data, which can act as a catalyst for potentially paradigm-shifting research. We aimed to identify the impact of major U.S. military campaigns on military neurosurgery literature across defined time periods.A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies from 1915 to 2021 relevant to military neurosurgery. A discrete set of validated informetric metadata parameters were extracted and analyzed using productivity analysis, citation analysis, keyword analysis, text mining, content analysis, and collaboration network mapping.Our search yielded 2216 documents. Annual scientific production since 1915 grew at a compounded rate of 6.1% per year, with the most significant increases during U.S. military campaigns (coefficient = 42.9, P0.001) and following the introduction of the Department of Defense Trauma Registry in 2007 (coefficient = 114.5; P0.001). Each war had a direct influence on military neurosurgery literature growth (P0.05), with the most prominent following the Afghanistan war. The journals with the most publications on military neurosurgery were Military Medicine (n = 168) and Journal of Head Trauma. The topmost cited author was Hoge et al. (N = 2083), while the topmost cited country was the United States (N = 1098).Since World War II, the military has contributed significant historical developments to neurosurgery, the most prominent being after the Iraq and Afghanistan wars and the introduction of the Department of Defense Trauma Registry.

Published
2022
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7. The Impact of Preinjury Antiplatelet and Anticoagulant Use on Elderly Patients with Moderate or Severe Traumatic Brain Injury Following Traumatic Acute Subdural Hematoma

Author

Rory B. O'Donohoe, Hui Qing Lee, Terence Tan, Simon Hendel, Martin Hunn, Joseph Mathews, Mark Fitzgerald, Jeffrey V. Rosenfeld, and Jin Tee

Subjects
Male, Anticoagulants, Glasgow Outcome Scale, Hematoma, Subdural, Treatment Outcome, Brain Injuries, Traumatic, Hematoma, Subdural, Intracranial, Hematoma, Subdural, Acute, Humans, Female, Surgery, Neurology (clinical), Aged, Retrospective Studies
Abstract

Although it is often assumed that preinjury anticoagulant (AC) or antiplatelet (AP) use is associated with poorer outcomes among those with acute subdural hematoma (aSDH), previous studies have had varied results. This study examines the impact of preinjury AC and AP therapy on aSDH thickness, 30-day mortality, and extended Glasgow Outcome Scale at 6 months in elderly patients (aged ≥65).A level 1 trauma center registry was interrogated to identify consecutive elderly patients who presented with moderate or severe traumatic brain injury (TBI) and associated traumatic aSDH between the first of January 2013 and the first of January 2018. Relevant demographic, clinical, and radiological data were retrieved from institutional medical records. The 3 primary outcome measures were aSDH thickness on initial computed tomography scan, 30-day mortality, and unfavorable outcome at 6 months (extended Glasgow Outcome Scale).One hundred thirty-two elderly patients were admitted with moderate or severe TBI and traumatic aSDH. The mean (±SD) age was 78.39 (±7.87) years, and a majority of patients (59.8%, n = 79) were male. There was a statistically significant difference in mean aSDH thickness, but there were no significant differences in 30-day mortality (P = 0.732) and unfavorable outcome between the AP, AC, combined AP and AC, and no antithrombotic exposure groups (P = 0.342).Further studies with larger sample sizes are necessary to confirm these observations, but our findings do not support the preconceived notion in clinical practice that antithrombotic use is associated with poor outcomes in elderly patients with moderate or severe TBI.

Published
2022
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9. The role of tranexamic acid in traumatic brain injury

Author

Stephen, Honeybul, Kwok M, Ho, and Jeffrey V, Rosenfeld

Subjects
Tranexamic Acid, Neurology, Fibrinolysis, Physiology (medical), Brain Injuries, Traumatic, Humans, Thrombosis, Surgery, Neurology (clinical), General Medicine, Antifibrinolytic Agents
Abstract

Evidence from recent trials evaluating efficacy of antifibrinolytic agents in the context of traumatic brain injury may lead to changes in the management of patients with traumatic brain injury. Tranexamic acid (TXA) reduces the proteolytic action of plasmin on fibrin clots, resulting in an inhibition of fibrinolysis and stabilisation of established blood clots. There has been significant interest in use of the drug as a therapeutic agent in the context of severe haemorrhage; however, considerable controversies regarding its efficacy remain. A number of trials have demonstrated a small but significant decrease in mortality following its administration, but the results have been somewhat inconsistent and may not be generalisable. The results of the CRASH-3 trial were that there was no statistical difference in the number of traumatic brain injury related deaths (18.5% with TXA and 19.8% with placebo; relative risk [RR] 0·94; 95% confidence interval [CI] 0·86-1·02). Nonetheless, there was a subgroup of patients for whom TXA appeared to provide benefit, and this was in patients with mild and moderate injury (with a Glasgow Coma Score 8). This is potentially a very important finding that may have huge potential implications; however, we believe it does not currently provide indisputable evidence to support the administration of TXA to all patients with TBI. Further work is required to better define the subset of patients who may benefit as well as to evaluate the long-term functional benefit in order to determine which types of severe traumatic brain injury patients would derive more benefits than harms from TXA.

Published
2022
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10. The association of padded headgear with concussion and injury risk in junior Australian football: A prospective cohort study

Author

Catherine Willmott, Patrick Clifton, Jeffrey V. Rosenfeld, Teresa Howard, Jennifer Makovec Knight, Andrew S. McIntosh, Michael Makdissi, Biswadev Mitra, and Peter Harcourt

Subjects
Male, medicine.medical_specialty, Football, Physical Therapy, Sports Therapy and Rehabilitation, Internal medicine, Concussion, medicine, Humans, Injury risk, Orthopedics and Sports Medicine, Prospective Studies, Prospective cohort study, Brain Concussion, business.industry, Incidence, Incidence (epidemiology), Head injury, Australia, medicine.disease, Athletic Injuries, Female, Head Protective Devices, Body region, Medical assessment, business, human activities
Abstract

To assess whether padded headgear was associated with incidence of suspected sports-related concussion, non-sports-related concussion head injury, and injuries to other body regions in junior Australian football.Prospective cohort injury surveillance.There were 400 junior players (42.5% female) enrolled across two seasons. Suspected sports-related concussion was defined by detection of observable signs on the field and medical assessment or missed match(es) due to suspected sports-related concussion. Non-sports-related concussion head injury and injuries to other body regions were defined as those that received medical assessment or resulted in a missed match.There were 20 teams monitored over 258 matches. 204 players (2484 player hours) wore mandated headgear throughout the season and 196 (2246 player hours) did not. The incidence rate of suspected sports-related concussion was 3.17 (95% confidence interval: 3.04-3.30) per 1000 player-hours and no differences were observed between males and females (risk ratio 1.11; 95% confidence interval: 0.40-3.06). Headgear use was not associated with suspected sports-related concussion (risk ratio 1.09; 95% confidence interval: 0.41-2.97), non-sports-related concussion head injury (risk ratio 0.27; 95% confidence interval: 0.06-1.31), or injuries to other body regions (risk ratio 1.41; 95% confidence interval: 0.79-2.53).Headgear use was not associated with reduced risk of suspected sports-related concussion, non-sports-related concussion head injury or injuries to other body regions. There was no difference in the rate of suspected sports-related concussion in female compared to male players, however, rates of non-sports-related concussion head injury and injuries to other body regions were higher in male players.

Published
2022
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11. The complete sequence of a human genome

Author

Sergey Nurk, Sergey Koren, Arang Rhie, Mikko Rautiainen, Andrey V. Bzikadze, Alla Mikheenko, Mitchell R. Vollger, Nicolas Altemose, Lev Uralsky, Ariel Gershman, Sergey Aganezov, Savannah J. Hoyt, Mark Diekhans, Glennis A. Logsdon, Michael Alonge, Stylianos E. Antonarakis, Matthew Borchers, Gerard G. Bouffard, Shelise Y. Brooks, Gina V. Caldas, Nae-Chyun Chen, Haoyu Cheng, Chen-Shan Chin, William Chow, Leonardo G. de Lima, Philip C. Dishuck, Richard Durbin, Tatiana Dvorkina, Ian T. Fiddes, Giulio Formenti, Robert S. Fulton, Arkarachai Fungtammasan, Erik Garrison, Patrick G. S. Grady, Tina A. Graves-Lindsay, Ira M. Hall, Nancy F. Hansen, Gabrielle A. Hartley, Marina Haukness, Kerstin Howe, Michael W. Hunkapiller, Chirag Jain, Miten Jain, Erich D. Jarvis, Peter Kerpedjiev, Melanie Kirsche, Mikhail Kolmogorov, Jonas Korlach, Milinn Kremitzki, Heng Li, Valerie V. Maduro, Tobias Marschall, Ann M. McCartney, Jennifer McDaniel, Danny E. Miller, James C. Mullikin, Eugene W. Myers, Nathan D. Olson, Benedict Paten, Paul Peluso, Pavel A. Pevzner, David Porubsky, Tamara Potapova, Evgeny I. Rogaev, Jeffrey A. Rosenfeld, Steven L. Salzberg, Valerie A. Schneider, Fritz J. Sedlazeck, Kishwar Shafin, Colin J. Shew, Alaina Shumate, Ying Sims, Arian F. A. Smit, Daniela C. Soto, Ivan Sović, Jessica M. Storer, Aaron Streets, Beth A. Sullivan, Françoise Thibaud-Nissen, James Torrance, Justin Wagner, Brian P. Walenz, Aaron Wenger, Jonathan M. D. Wood, Chunlin Xiao, Stephanie M. Yan, Alice C. Young, Samantha Zarate, Urvashi Surti, Rajiv C. McCoy, Megan Y. Dennis, Ivan A. Alexandrov, Jennifer L. Gerton, Rachel J. O’Neill, Winston Timp, Justin M. Zook, Michael C. Schatz, Evan E. Eichler, Karen H. Miga, Adam M. Phillippy, Nurk, Sergey [0000-0003-1301-5749], Koren, Sergey [0000-0002-1472-8962], Rhie, Arang [0000-0002-9809-8127], Rautiainen, Mikko [0000-0003-2971-267X], Bzikadze, Andrey V [0000-0002-7928-7950], Vollger, Mitchell R [0000-0002-8651-1615], Altemose, Nicolas [0000-0002-7231-6026], Uralsky, Lev [0000-0002-5565-7961], Gershman, Ariel [0000-0001-8899-8781], Aganezov, Sergey [0000-0003-2458-8323], Hoyt, Savannah J [0000-0001-7804-3236], Diekhans, Mark [0000-0002-0430-0989], Logsdon, Glennis A [0000-0003-2396-0656], Alonge, Michael [0000-0002-3692-1819], Antonarakis, Stylianos E [0000-0001-8907-5823], Borchers, Matthew [0000-0001-5903-3489], Bouffard, Gerard G [0000-0001-8744-6440], Chen, Nae-Chyun [0000-0002-4140-4568], Cheng, Haoyu [0000-0002-9209-5793], Chin, Chen-Shan [0000-0003-4394-2455], Chow, William [0000-0002-9056-201X], de Lima, Leonardo G [0000-0001-6340-6065], Dishuck, Philip C [0000-0003-2223-9787], Durbin, Richard [0000-0002-9130-1006], Fiddes, Ian T [0000-0002-1580-7443], Formenti, Giulio [0000-0002-7554-5991], Fungtammasan, Arkarachai [0000-0003-2398-0358], Garrison, Erik [0000-0003-3821-631X], Grady, Patrick GS [0000-0003-0180-7810], Graves-Lindsay, Tina A [0000-0002-0409-891X], Hall, Ira M [0000-0003-4442-6655], Hansen, Nancy F [0000-0002-0950-0699], Haukness, Marina [0000-0001-9991-8089], Howe, Kerstin [0000-0003-2237-513X], Jain, Miten [0000-0002-4571-3982], Jarvis, Erich D [0000-0001-8931-5049], Kirsche, Melanie [0000-0002-6631-4761], Kolmogorov, Mikhail [0000-0002-5489-9045], Korlach, Jonas [0000-0003-3047-4250], Kremitzki, Milinn [0000-0001-7980-3153], Li, Heng [0000-0003-4874-2874], Maduro, Valerie V [0000-0001-8250-9844], Marschall, Tobias [0000-0002-9376-1030], McDaniel, Jennifer [0000-0003-1987-0914], Miller, Danny E [0000-0001-6096-8601], Mullikin, James C [0000-0003-0825-3750], Myers, Eugene W [0000-0002-6580-7839], Olson, Nathan D [0000-0003-2585-3037], Paten, Benedict [0000-0001-8863-3539], Pevzner, Pavel A [0000-0002-0418-165X], Porubsky, David [0000-0001-8414-8966], Potapova, Tamara [0000-0003-2761-1795], Rosenfeld, Jeffrey A [0000-0002-8750-2841], Salzberg, Steven L [0000-0002-8859-7432], Sedlazeck, Fritz J [0000-0001-6040-2691], Shafin, Kishwar [0000-0001-5252-3434], Shumate, Alaina [0000-0002-4450-1857], Smit, Arian FA [0000-0003-2088-3165], Soto, Daniela C [0000-0002-6292-655X], Sović, Ivan [0000-0002-5900-4319], Storer, Jessica M [0000-0002-9619-5265], Streets, Aaron [0000-0002-3909-8389], Sullivan, Beth A [0000-0001-5216-4603], Thibaud-Nissen, Françoise [0000-0003-4957-7807], Torrance, James [0000-0002-6117-8190], Walenz, Brian P [0000-0001-8431-1428], Wenger, Aaron [0000-0003-1183-0432], Wood, Jonathan MD [0000-0002-7545-2162], Xiao, Chunlin [0000-0001-8702-4889], Yan, Stephanie M [0000-0002-6880-465X], Young, Alice C [0000-0003-0549-9261], Zarate, Samantha [0000-0001-5570-2059], McCoy, Rajiv C [0000-0003-0615-146X], Dennis, Megan Y [0000-0002-8502-5420], Alexandrov, Ivan A [0000-0003-4342-2003], Gerton, Jennifer L [0000-0003-0743-3637], O'Neill, Rachel J [0000-0002-1525-6821], Timp, Winston [0000-0003-2083-6027], Zook, Justin M [0000-0003-2309-8402], Schatz, Michael C [0000-0002-4118-4446], Eichler, Evan E [0000-0002-8246-4014], Miga, Karen H [0000-0001-9709-4565], Phillippy, Adam M [0000-0003-2983-8934], and Apollo - University of Cambridge Repository

Subjects
Chromosomes, Artificial, Bacterial, Genome, Multidisciplinary, General Science & Technology, Genome, Human, 1.1 Normal biological development and functioning, Human Genome, Bacterial, DNA, Sequence Analysis, DNA, Chromosomes, Cell Line, Underpinning research, Reference Values, Artificial, Human Genome Project, Genetics, Chromosomes, Human, Humans, Generic health relevance, Sequence Analysis, Human
Abstract

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

Published
2022
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12. Tumor characteristics and surgical outcomes of intracranial subependymomas: a systematic review and meta-analysis

Author

Barry Ting Sheen Kweh, Martin Hunn, Jin Wee Tee, and Jeffrey V. Rosenfeld

Subjects
Male, medicine.medical_specialty, business.industry, Mortality rate, medicine.medical_treatment, Retrospective cohort study, General Medicine, Fourth ventricle, Subependymoma, medicine.disease, Survival Rate, Radiation therapy, Treatment Outcome, Glioma, Subependymal, Lateral Ventricles, Meta-analysis, Internal medicine, Humans, Medicine, Female, business, Survival rate, Pathological, Retrospective Studies
Abstract

OBJECTIVE The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. METHODS A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. RESULTS Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39–7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03–7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78–2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35–1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27–2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). CONCLUSIONS Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

Published
2022
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13. Visible Signs of Concussion and Cognitive Screening in Community Sports

Author

Patrick Clifton, Jack V. K. Nguyen, Brendan P Major, Michael Makdissi, Biswadev Mitra, Jeffrey V. Rosenfeld, Peter Cameron, Peter Harcourt, Jonathan Reyes, Teresa S. Howard, and Catherine Willmott

Subjects
Male, medicine.medical_specialty, Medical staff, Traumatic brain injury, business.industry, Australia, Football, Cognition, medicine.disease, Sport related concussion, Head trauma, Physical medicine and rehabilitation, Athletic Injuries, Concussion, Cognitive screening, medicine, Humans, Female, Prospective Studies, Neurology (clinical), business, human activities, Brain Concussion
Abstract

Video surveillance and detection of players with visible signs of concussion by experienced medical staff facilitates rapid on-field screening of suspected concussion in professional sports. This method, however has not been validated in community sports where video footage is unavailable. This study aimed to explore the utility of visible signs of concussion to identify players with decrements in performance on concussion screening measures. In this observational prospective cohort study, personnel with basic training observed live matches across a season (60 matches) of community male and female Australian football for signs of concussion outlined in the community-based Head Injury Assessment form (HIAf). Players identified to have positive signs of concussion (CoSign+) following an impact were compared with players without signs (CoSign-). Outcome measures, the Sport Concussion Assessment Tool (SCAT3) and Cogstate, were administered at baseline and post-match. CoSign+ (

Published
2022
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14. Micro-RNA levels and symptom profile after mild traumatic brain injury: A longitudinal cohort study

Author

Biswadev Mitra, Jonathan Reyes, William T. O'Brien, Nanda Surendran, Annie Carter, Jesse Bain, Laura McEntaggart, Edmond Sorich, Sandy R. Shultz, Terence J. O'Brien, Catherine Willmott, Jeffrey V. Rosenfeld, and Stuart J. McDonald

Subjects
MicroRNAs, Neurology, Post-Concussion Syndrome, Physiology (medical), Humans, Surgery, Longitudinal Studies, Prospective Studies, Neurology (clinical), General Medicine, Brain Concussion
Abstract

Micro riboneucleic acids (miRNAs) may be transcribed after brain injury and be detectable in plasma. This study aimed to assess the discriminative ability of seven miRNAs in plasma to differentiate between patients with mild traumatic brain injury (mTBI) and healthy controls. Changes in miRNA levels over 28 days were compared to changes in self-reported symptom profile. This was a prospective cohort study with longitudinal measurements of miRNA levels and symptom self-report. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) was used to determine symptom severity. Mean normalised expression ratios (NER) of miRNAs at day 0 between mTBI and healthy controls were compared. An analysis of response profiles compared the response over time of miRNA species with RPQ symptom severity. miRNA levels of subjects who were defined to have "recovered" on Day 7 and 28 were compared to "non-recovered" subjects. There were 28 mTBI patients and 30 healthy controls included for analysis. Symptom severity was significantly higher on the day of injury among mTBI subjects (p 0.001), and miRNA 32-5p levels were also higher (p = 0.009). Change of miRNA levels were similar to RPQ change at Day 7, but significantly different at Day 28. Differences were observed among miRNA levels of recovered subjects. This study demonstrated differences in miRNA levels among mTBI subjects compared to healthy controls and different miRNA levels among those who had recovered compared to those reporting symptoms. The change in profiles of miRNAs was different to symptom severity, suggesting that the two measures reflect different aspects of brain injury and recovery.

Published
2022
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15. Is antibiotic treatment effective in the management of chronic low back pain with disc herniation?

Author

Donna M. Urquhart, Andrew Forbes, Patrick Chan, Jeffrey V. Rosenfeld, Flavia M. Cicuttini, Karin Leder, Richard O'Sullivan, Allen C. Cheng, Maurits W. van Tulder, Susan Liew, Anita E. Wluka, Faculty of Behavioural and Movement Sciences, AMS - Musculoskeletal Health, APH - Methodology, and APH - Societal Participation & Health

Subjects
Medicine (General), medicine.medical_specialty, Modic change, Visual analogue scale, medicine.drug_class, Antibiotics, Medicine (miscellaneous), Placebo, law.invention, Study Protocol, R5-920, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Rating scale, medicine, Humans, Pharmacology (medical), Low back pain, Pain Measurement, Randomized Controlled Trials as Topic, Disc herniation, Randomised controlled trial, business.industry, Australia, Modic changes, Anti-Bacterial Agents, Clinical trial, Treatment Outcome, Physical therapy, medicine.symptom, Chronic Pain, business
Abstract

Background There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. Methods One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. Discussion There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12615000958583. Registered on 11 September 2015

Published
2021
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16. Considering Futility of Care Decisions in Neurosurgical Practice

Author

Stephen Honeybul, Sara H. Olson, and Jeffrey V. Rosenfeld

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neurosurgery, COVID-19, medicine.disease, Intensive care unit, law.invention, law, Health care, Pandemic, medicine, Humans, Surgery, Neurology (clinical), Medical emergency, business, Medical Futility, Limited resources
Abstract

Neurosurgeons commonly encounter futility of care decisions in their practice. Are these decisions being made with adequate consideration? What is the preparation of neurosurgical trainees for making these decisions? The advent of the COVID-19 pandemic with its extreme pressure on resources and, in particular, intensive care unit beds, has prompted many health care providers including neurosurgeons to consider more fully the potentially futile nature of some treatments and how we might better manage limited resources for the future. We review the concept of futility in neurosurgery and suggest potential solutions to the multiple challenges that arise.

Published
2021
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17. A Randomized Controlled Trial of the Prevent Alcohol and Risk-Related Trauma in Youth Program in Reducing Alcohol-Related Harms in Young Naval Trainees

Author

Jeffrey V. Rosenfeld, Belinda J. Gabbe, Paul Dietze, and Jason Watterson

Subjects
medicine.medical_specialty, Alcohol Use Disorders Identification Test, business.industry, Hazard ratio, Public Health, Environmental and Occupational Health, General Medicine, Audit, Affect (psychology), law.invention, Test (assessment), Randomized controlled trial, law, Intervention (counseling), Relative risk, Physical therapy, Medicine, business
Abstract

Background The aim of this study was to test whether participation in an alcohol risk reduction program known as Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.) is effective in reducing the prevalence of risky drinking at 12 months’ post-intervention in a sample of Royal Australian Navy (RAN) trainees. Methods A non-blinded randomized controlled trial of 952 RAN trainees comparing two forms of P.A.R.T.Y. plus RAN annual alcohol and other drug awareness training with annual alcohol and other drugs awareness training only (Control). Participants were screened at baseline and at 12-month follow-up using the Alcohol Use Disorders Identification Test (AUDIT). Participants were randomized to one of three arms: (1) in-hospital P.A.R.T.Y program, (2) on-base P.A.R.T.Y. program, or (3) control. The primary outcome measure was the percentage of participants reporting an AUDIT score of 8 or above at 12 months in each group. A secondary outcome considered was reports of alcohol-related incidents in the 12-month follow-up. Results There was no difference in the risk of reporting an AUDIT score of 8 or above in either the in-hospital (Relative Risk (RR) 0.96, 95% CI: 0.75-1.23; P = .75) or on-base (RR 1.11, 95% CI: 0.89-1.369; P = 0.35) intervention groups, compared to the control group. Compared to the on-base group, there was no difference in the risk of reporting an AUDIT score of 8 or above in the in-hospital group (RR 1.16, 95% CI: 0.90-1.48; P = .24). The rate of reporting an alcohol-related incident was not different for the in-hospital (Hazard Ratio (HR) 0.60, 95% CI: 0.27-1.33; P = .21) or on-base (HR 0.50, 95% CI: 0.21-1.16; P = .11) intervention groups when compared to the control group. Conclusion Participation in either an on-base or an in-hospital P.A.R.T.Y. program did not affect the proportion of naval trainee participants screening positive for risky drinking on the AUDIT.

Published
2021
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19. Benchmarking challenging small variants with linked and long reads

Author

Justin Wagner, Nathan D. Olson, Lindsay Harris, Ziad Khan, Jesse Farek, Medhat Mahmoud, Ana Stankovic, Vladimir Kovacevic, Byunggil Yoo, Neil Miller, Jeffrey A. Rosenfeld, Bohan Ni, Samantha Zarate, Melanie Kirsche, Sergey Aganezov, Michael C. Schatz, Giuseppe Narzisi, Marta Byrska-Bishop, Wayne Clarke, Uday S. Evani, Charles Markello, Kishwar Shafin, Xin Zhou, Arend Sidow, Vikas Bansal, Peter Ebert, Tobias Marschall, Peter Lansdorp, Vincent Hanlon, Carl-Adam Mattsson, Alvaro Martinez Barrio, Ian T. Fiddes, Chunlin Xiao, Arkarachai Fungtammasan, Chen-Shan Chin, Aaron M. Wenger, William J. Rowell, Fritz J. Sedlazeck, Andrew Carroll, Marc Salit, and Justin M. Zook

Abstract

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as

Published
2022

20. RNA-seq profile of African American men with a clinically localized prostate cancer

Author

Isaac Yi Kim, Naoya Nagaya, Jeffrey A. Rosenfeld, and Geun Taek Lee

Subjects
Biochemical recurrence, Oncology, medicine.medical_specialty, Urology, medicine.medical_treatment, 030232 urology & nephrology, RNA-Seq, Caucasian, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Internal medicine, Gene expression, medicine, African American, Gene, Prostatectomy, business.industry, RNA, medicine.disease, Diseases of the genitourinary system. Urology, 030220 oncology & carcinogenesis, Cohort, RC870-923, RNA-seq, business, Research Article
Abstract

Background Prostate cancer in African American (AA) men has a poor prognosis. This study aimed to identify potential genetic risk factors for prostate cancer in AA men. Methods We used prostate cancer tissue from 61 patients who underwent radical prostatectomy. We compared somatic gene expression in Caucasian (CA) and AA men using RNA sequencing. Results By comparing the RNA-seq data obtained from prostate cancer tissue between AA and CA men, this study showed a significant difference in expression levels of 45 genes. Pathway analysis of 45 genes using Kyoto Encyclopedia of Genes and Genomesenrichment analysis revealed a neuroactive ligand-receptor interaction signal. In addition, the results of the Ingenuity Pathway Analysis showed pathways involved sphingosine-1-phosphate signaling. Furthermore, validating 45 genes in the The Cancer Genome Atlas (TCGA) Provisional cohort, cholinergic receptor muscarinic 3 expression level was significantly lower in AA than in CA men, and the results showed a significantly higher rate of biochemical recurrence in patients with low expression. Conclusions We identified genetic differences of clinically localized prostate cancer in AAs and CAs by RNA sequencing.

Published
2021

21. 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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24. The Effects of Surgery and Adjuvant Therapy on Survival Outcomes in Clear Cell Ependymomas: A Systematic Review and Meta-Analysis of Individual Patient Data

Author

Jin Wee Tee, Barry Ting Sheen Kweh, Jeffrey V. Rosenfeld, and Martin Hunn

Subjects
Prognostic variable, medicine.medical_specialty, Kaplan-Meier Estimate, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Adjuvant therapy, medicine, Humans, Progression-free survival, Survival analysis, Brain Neoplasms, Proportional hazards model, business.industry, Chemoradiotherapy, Adjuvant, Combined Modality Therapy, Survival Analysis, Progression-Free Survival, Confidence interval, Surgery, Treatment Outcome, Ependymoma, 030220 oncology & carcinogenesis, Meta-analysis, Neurology (clinical), business, 030217 neurology & neurosurgery, Clear cell
Abstract

The survival outcomes of clear cell ependymomas are poorly understood. This study clarifies the role of surgery and adjuvant therapy when this morphologically distinct tumor is encountered.A systematic search for studies relating to clear cell ependymomas was conducted. Primary outcomes were progression-free survival and overall survival. Prognostic variables were age, sex, tumor consistency, extent of resection, and postoperative adjuvant therapy. Kaplan-Meier survival curves were generated and compared by the log-rank test. Multivariate Cox regression models were constructed, interrogated with Schoenfeld residuals, and used to identify independent prognostic factors.Of the 384 articles retrieved, 8 articles comprising 77 cases of clear cell ependymoma were included. Five-year overall survival and progression-free survival were 58.1% (95% confidence interval [CI], 46.3%-72.9%) and 46.3% (95% CI, 34.2%-62.8%), respectively. Kaplan-Meier analysis with the log-rank test showed that gross total resection was superior to subtotal resection in prolonging survival (P = 0.047) and delayed time to recurrence (P0.01). Multivariate analysis confirmed gross total resection as an independent protective factor against relapse (odds ratio, 0.39; 95% CI, 0.17-0.89; P = 0.03). Age50 years predicted longer overall survival (odds ratio, 0.16; 95% CI, 0.05-0.49; P0.01). Postoperative adjuvant therapy after gross total resection did not affect overall survival (P = 0.98) or progression-free survival (P = 0.93). Adjuvant therapy after subtotal resection favored improved overall survival (P = 0.052).Clear cell ependymomas are particularly aggressive in those aged50 years. Gross total resection remains the cornerstone of management. Postoperative adjuvant therapy is likely to be of survival benefit only after subtotal resection.

Published
2021
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25. The Utility of the Modified Frailty Index in Outcome Prediction for Elderly Patients with Acute Traumatic Subdural Hematoma

Author

Caleb Tan, Joseph P. Mathew, Martin Hunn, Hui Lee, Andrew A. Udy, Ronald Leong, Jeffrey V. Rosenfeld, Mark Fitzgerald, Tony Kambourakis, Dashiell Gantner, Jin Tee, and Vanessa Tran

Subjects
Male, 030506 rehabilitation, medicine.medical_specialty, Frailty Index, Glasgow Outcome Scale, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Hematoma, Subdural, Intracranial, Hematoma, Subdural, Acute, Humans, Medicine, Aged, Aged, 80 and over, Frailty, business.industry, Recovery of Function, Prognosis, medicine.disease, Subdural Hematomas, Surgery, Female, Neurology (clinical), 0305 other medical science, business, Outcome prediction, Acute subdural hematoma, 030217 neurology & neurosurgery
Abstract

This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% (

Published
2020
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26. Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury

Author

Chiara Robba, Paola Rebora, Erika Banzato, Eveline J.A. Wiegers, Nino Stocchetti, David K. Menon, Giuseppe Citerio, Cecilia Åkerlund, David Nelson, Krisztina Amrein, József Nyirádi, Nada Andelic, Lasse Andreassen, Audny Anke, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Luigi Beretta, Maria Rosa Calvi, Ronald Bartels, Hugo den Boogert, Ronny Beer, Raimund Helbok, Bo-Michael Bellander, Habib Benali, Vincent Degos, Damien Galanaud, Vincent Perlbarg, Audrey Vanhaudenhuyse, Maurizio Berardino, Morten Blaabjerg, Stine Borgen Lund, Camilla Brorsson, Andras Buki, Endre Czeiter, Manuel Cabeleira, Marek Czosnyka, Peter Smielewski, Alessio Caccioppola, Emiliana Calappi, Marco Carbonara, Davide Mulazzi, Fabrizio Ortolano, Tommaso Zoerle, Peter Cameron, Dashiell Gantner, Lynnette Murray, Tony Trapani, Shirley Vallance, Guillermo Carbayo Lozano, Inigo Pomposo, Ana M. Castaño-León, Pedro A. Gomez, Alfonso Lagares, Giorgio Chevallard, Arturo Chieregato, Mark Coburn, Ana Kowark, Rolf Rossaint, Jonathan Coles, Jamie D. Cooper, Marta Correia, Claire Dahyot-Fizelier, Véronique De Keyser, Andrew I.R. Maas, Tomas Menovsky, Nandesh Nair, Gregory Van der Steen, Francesco Della Corte, Francesca Grossi, Bart Depreitere, Dula Dilvesi, Jagos Golubovic, Mladen Karan, Petar Vulekovic, Abhishek Dixit, Ari Ercole, Evgenios Koraropoulos, David Menon, Virginia Newcombe, Sophie Richter, Emmanuel Stamatakis, Guy Williams, Stefan Winzeck, Frederik A. Zeiler, Jens Dreier, Guy-Loup Dulière, Hugues Maréchal, Erzsébet Ezer, Zoltán Vámos, Martin Fabricius, Daniel Kondziella, Kelly Foks, Shirin Frisvold, Alex Furmanov, Guy Rosenthal, Alexandre Ghuysen, Lelde Giga, Egils Valeinis, Agate Ziverte, Deepak Gupta, Iain Haitsma, Victor Volovici, Eirik Helseth, Peter J. Hutchinson, Angelos G. Kolias, Stefan Jankowski, Lars-Owe Koskinen, Noémi Kovács, Steven Laureys, Quentin Noirhomme, Aurelie Lejeune, Emmanuel Vega, Roger Lightfoot, Ewout W. Steyerberg, Hester Lingsma, Daphne Voormolen, Alex Manara, Matt Thomas, Costanza Martino, Julia Mattern, Oliver Sakowitz, Alexander Younsi, Catherine McMahon, Visakh Muraleedharan, Ancuta Negru, Horia Ples, Cristina Maria Tudora, Jean-François Payen, Paolo Persona, Sandra Rossi, Wilco Peul, Jeroen T.J. M. van Dijck, Thomas A. van Essen, Roel P.J. van Wijk, Anna Piippo-Karjalainen, Rahul Raj, Jussi P. Posti, Olli Tenovuo, Louis Puybasset, Andreea Radoi, Juan Sahuquillo, Arminas Ragauskas, Saulius Rocka, Jonathan Rhodes, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Oddrun Sandro, Kari Schirmer-Mikalsen, Renan Sanchez-Porras, Anne Vik, Rico Frederik Schou, Abayomi Sorinola, Viktória Tamás, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Dick Tibboel, Christos Tolias, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, and Stefan Wolf

Subjects
Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, Longitudinal study, Traumatic brain injury, business.industry, medicine.medical_treatment, Incidence (epidemiology), Glasgow Outcome Scale, Ventilator-associated pneumonia, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, Clinical trial, Interquartile range, Emergency medicine, medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Background No large prospective data, to our knowledge, are available on ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI). Research Question To evaluate the incidence, timing, and risk factors of VAP after TBI and its effect on patient outcome. Study Design and Methods This analysis is of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury data set, from a large, multicenter, prospective, observational study including patients with TBI admitted to European ICUs, receiving mechanical ventilation for ≥ 48 hours and with an ICU length of stay (LOS) ≥ 72 hours. Characteristics of patients with VAP vs characteristics of patients without VAP were compared, and outcome was assessed at 6 months after injury by using the Glasgow Outcome Scale Extended. Results The study included 962 patients: 196 (20.4%) developed a VAP at a median interval of 5 days (interquartile range [IQR], 3-7 days) after intubation. Patients who developed VAP were younger (median age, 39.5 [IQR, 25-55] years vs 51 [IQR, 30-66] years; P Interpretation VAP occurs less often than previously described in patients after TBI and has a detrimental effect on ICU LOS but not on mortality and neurological outcome. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02210221; URL: www.clinicaltrials.gov

Published
2020
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27. Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury

Author

Louis Jacob, Mélanie Cogné, Olli Tenovuo, Cecilie Røe, Nada Andelic, Marek Majdan, Jukka Ranta, Peter Ylen, Helen Dawes, Philippe Azouvi, Cecilia Åkerlund, Krisztina Amrein, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó9, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Jacob, L., Cogne, M., Tenovuo, O., Roe, C., Andelic, N., Majdan, M., Ranta, J., Ylen, P., Dawes, H., Azouvi P., (CENTER-TBI Participants and Investigators), Beretta, Luigi, Jacob, L, Cogne, M, Tenovuo, O, Roe, C, Andelic, N, Majdan, M, Ranta, J, Ylen, P, Dawes, H, Azouvi, P, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azzolini, M, Bartels, R, Barzo9, 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, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, 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, Maas, A, Castano-Leon, A, Maegele, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, van der Jagt, M, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vande Vyvere, T, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Oslo University Hospital [Oslo], Oxford Brookes University, European Commission, EC: 602150, The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Data used in preparation of this article were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC Grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA), and from Integra LifeSciences Corporation (USA). Data for the CENTER-TBI study were collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). The funder had no role in the study design, collection, analysis, and interpretation of the data, writing of the report, and the decision to submit the article for publication., European Project: 602150,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CENTER-TBI(2013), Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, and Psychiatrie & Neuropsychologie

Subjects
Male, 030506 rehabilitation, Neurology, predictive factors, IMPACT, medicine.medical_treatment, CENTER-TBI, Health Services Accessibility, 3124 Neurology and psychiatry, predictive factor, Injury Severity Score, 0302 clinical medicine, Brain Injuries, Traumatic, Epidemiology, EPIDEMIOLOGY, Prospective Studies, rehabilitation, OUTCOMES, Rehabilitation, traumatic brain injury, Neurological Rehabilitation, General Medicine, Middle Aged, RECOVERY, Prognosis, 3. Good health, Hospitalization, Europe, Educational Status, international prospective study, Female, HEALTH, 0305 other medical science, Adult, Employment, medicine.medical_specialty, Traumatic brain injury, 03 medical and health sciences, Sex Factors, medicine, Humans, Glasgow Coma Scale, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, MORTALITY, 3112 Neurosciences, PATHWAYS, CARE, medicine.disease, Multicenter study, Emergency medicine, MODERATE, business, 030217 neurology & neurosurgery
Abstract

BackgroundAlthough rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.ObjectiveTherefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.MethodsData from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.ResultsIn the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).ConclusionsBased on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.

Published
2020
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28. The potential of head acceleration measurement to augment current best practice in concussion screening in professional Australian football players

Author

Patrick Clifton, Peter Harcourt, Jonathan Reyes, Andrew S. McIntosh, Jeffrey V. Rosenfeld, Teresa Howard, Catherine Willmott, Jack V. K. Nguyen, Michael Makdissi, Peter Cameron, and Biswadev Mitra

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Acceleration, Football, Video Recording, Poison control, Pilot Projects, Physical Therapy, Sports Therapy and Rehabilitation, Suicide prevention, 03 medical and health sciences, 0302 clinical medicine, Accelerometry, Injury prevention, Concussion, medicine, Humans, Orthopedics and Sports Medicine, Prospective Studies, Brain Concussion, 030222 orthopedics, Rehabilitation, business.industry, Australia, Human factors and ergonomics, 030229 sport sciences, General Medicine, medicine.disease, Physical therapy, Female, Observational study, business, Head, human activities
Abstract

Objective To explore the potential utility of head acceleration event (HAE) measurements to augment identification of players for further concussion screening in non-helmeted contact sport. Design Prospective observational pilot study. Participants 210 (118 female) professional Australian football players in 2017 season. Methods Players wore the X-Patch® accelerometer for one match each with data collected across 14 matches. Players with HAEs above thresholds associated with concussion, 95 g (males) or 85.5 g (females), were compared to players identified to have suspected concussion by club personnel during the inspected matches. Video review of matches was undertaken by a physician blinded to HAEs to identify players with concussive signs. Results Among 26 players (50% female) with HAEs above threshold, two players were screened for concussion. Of the remaining 24 players, nine were not visible on video at the HAE time, six sustained verifiable head impacts, and nine sustained verifiable body impacts with no head impacts. Among 184 players with HAEs below threshold, five players were screened. Conclusion Players were identified to have head impacts and suspected concussion in the absence of HAEs above threshold. Use of X-Patch® was not sufficiently reliable for identifying players for further concussion screening in professional Australian football. Video review of head impacts remains essential in concussion screening.

Published
2020
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29. Aggressive FUS-Mutant Motor Neuron Disease Without Profound Spinal Cord Pathology

Author

Craig W. Zuppan, Jeffrey V. Rosenfeld, Yan Chen Wongworawat, Yin Allison Liu, Robin Dietz, Ravi Raghavan, and Charles L. White

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Cord, Autopsy, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Atrophy, Anterior Horn Cell, Exome Sequencing, Humans, Medicine, Motor Neuron Disease, Amyotrophic lateral sclerosis, 030304 developmental biology, Neurons, Denervation, 0303 health sciences, business.industry, General Medicine, Motor neuron, medicine.disease, Spinal cord, medicine.anatomical_structure, Spinal Cord, Neurology, Mutation, Disease Progression, RNA-Binding Protein FUS, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

A 29-year-old man presented with rapidly progressive severe neck weakness, asymmetrical bilateral upper extremity weakness, bulbar dysfunction, profound muscle wasting, and weight loss. Within 1 year, his speech became unintelligible, he became gastrostomy- and tracheostomy/ventilator-dependent, and wheelchair bound. Electrophysiology suggested motor neuron disease. Whole exome sequencing revealed a heterozygous pathogenic variant in the fused in sarcoma gene (FUS), c.1574C>T,p. R525L, consistent with autosomal dominant amyotrophic lateral sclerosis. Autopsy revealed extensive denervation atrophy of skeletal musculature. Surprisingly, there was only minimal patchy depletion of motor neurons within the cervico-thoracic spinal cord anterior horn cells, and the tracts were largely preserved. TDP-43 inclusions were absent. Abnormal expression of FUS mutation product (cytoplasmic inclusions) was demonstrated by immunohistochemistry within anterior horn motor neurons. The most prominent finding was a disparity between profound neck weakness and relatively low-grade anterior horn cell loss or tract degeneration in the cervico-thoracic cord.

Published
2020
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30. IGF2 drives formation of ileal neuroendocrine tumors in patients and mice

Author

Laura H. Tang, Chris R. Harris, Richard Clausen, Tanupriya Contractor, Grant R Harris, Darren R. Carpizo, and Jeffrey A. Rosenfeld

Subjects
Male, 0301 basic medicine, Cancer Research, Endocrinology, Diabetes and Metabolism, Transgene, Neuroendocrine tumors, Biology, medicine.disease_cause, Genomic Imprinting, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin-Like Growth Factor II, medicine, Animals, Humans, Allele, Imprinting (psychology), Gene, medicine.disease, Nuclear DNA, Ileal Neoplasms, Insulin-Like Growth Factor Binding Protein 1, Disease Models, Animal, Neuroendocrine Tumors, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, Genomic imprinting, Carcinogenesis
Abstract

By the strictest of definitions, a genetic driver of tumorigenesis should fulfill two criteria: it should be altered in a high percentage of patient tumors, and it should also be able to cause the same type of tumor to form in mice. No gene that fits either of these criteria has ever been found for ileal neuroendocrine tumors (I-NETs), which in humans are known for an unusual lack of recurrently mutated genes, and which have never been detected in mice. In the following report, we show that I-NETs can be generated by transgenic RT2 mice, which is a classic model for a genetically unrelated disease, pancreatic neuroendocrine tumors (PNETs). The ability of RT2 mice to generate I-NETs depended upon genetic background. I-NETs appeared in a B6AF1 genetic background, but not in a B6 background nor even in an AB6F1 background. AB6F1 and B6AF1 have identical nuclear DNA but can potentially express different allelic forms of imprinted genes. This led us to test human I-NETs for loss of imprinting, and we discovered that the IGF2 gene showed loss of imprinting and increased expression in the I-NETs of 57% of patients. By increasing IGF2 activity genetically, I-NETs could be produced by RT2 mice in a B6 genetic background, which otherwise never developed I-NETs. The facts that IGF2 is altered in a high percentage of patients with I-NETs and that I-NETs can form in mice that have elevated IGF2 activity, define IGF2 as the first genetic driver of ileal neuroendocrine tumorigenesis.

Published
2020
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31. Single-cell sperm transcriptomes and variants from fathers of children with and without autism spectrum disorder

Author

Jeffrey A. Rosenfeld, Delia Tomoiaga, Shristi Shrestha, Shawn Levy, Paul Feinstein, Vanessa Aguiar-Pulido, and Christopher E. Mason

Subjects
0301 basic medicine, endocrine system, lcsh:QH426-470, lcsh:Medicine, Biology, Predictive markers, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Genetic variation, Genetics, medicine, Molecular Biology, Genetics (clinical), reproductive and urinary physiology, 030219 obstetrics & reproductive medicine, Molecular medicine, urogenital system, lcsh:R, RNA, medicine.disease, Sperm, lcsh:Genetics, 030104 developmental biology, Autism spectrum disorder, Autism, Stem cell, Neurotypical
Abstract

The human sperm is one of the smallest cells in the body, but also one of the most important, as it serves as the entire paternal genetic contribution to a child. Investigating RNA and mutations in sperm is especially relevant for diseases such as autism spectrum disorders (ASD), which have been correlated with advanced paternal age. Historically, studies have focused on the assessment of bulk sperm, wherein millions of individual sperm are present and only high-frequency variants can be detected. Using 10× Chromium single-cell sequencing technology, we assessed the transcriptome from >65,000 single spermatozoa across six sperm donors (scSperm-RNA-seq), including two who fathered multiple children with ASD and four fathers of neurotypical children. Using RNA-seq methods for differential expression and variant analysis, we found clusters of sperm mutations in each donor that are indicative of the sperm being produced by different stem cell pools. Finally, we have shown that genetic variations can be found in single sperm.

Published
2020
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32. The legacy of Renaissance surgeon Giovanni Andrea Dalla Croce on the history of military surgery and neurosurgery

Author

Antonio Di Ieva and Jeffrey V. Rosenfeld

Subjects
Male, Surgeons, Military Personnel, Italy, History, 16th Century, Neurosurgery, Humans, Surgery, History, 19th Century, Neurology (clinical), General Medicine, Military Medicine, Neurosurgical Procedures
Abstract

Giovanni Andrea Dalla Croce was a Venetian physician who lived in the 16th century and was famous for his treatment of wounds, which was surprisingly modern. He was the military surgeon of the Venetian Republic’s naval fleet. In 1537, he published the Chirurgiae universalis opus absolutum (The absolute work on universal surgery) in Latin, then expanded and translated into vernacular Italian and published in 1574 with the title Cirugia universale e perfetta di tutte le parti pertinenti all’ottimo chirurgo (Universal and perfect surgery of all the parts necessary for the optimal surgeon). This monumental work was a comprehensive handbook of surgery, medicine, and the treatment of many kinds of wounds with techniques to be used on the battlefield. It is also notable for the inclusion of illustrations of various weapons and projectiles, for the most comprehensive description and illustrations of surgical instruments at that time, and for the first illustrations of a surgeon performing trephination of the skull in an operating room. Dalla Croce also considered the writings of his surgical forebears in formulating his own ideas. Dalla Croce was a leader of traumatology, a universal surgeon who exemplified the erudite Renaissance man, and left a tremendous legacy to military surgery of the 16th century and beyond.

Published
2022

33. A complete reference genome improves analysis of human genetic variation

Author

Sergey Aganezov, Stephanie M. Yan, Daniela C. Soto, Melanie Kirsche, Samantha Zarate, Pavel Avdeyev, Dylan J. Taylor, Kishwar Shafin, Alaina Shumate, Chunlin Xiao, Justin Wagner, Jennifer McDaniel, Nathan D. Olson, Michael E. G. Sauria, Mitchell R. Vollger, Arang Rhie, Melissa Meredith, Skylar Martin, Joyce Lee, Sergey Koren, Jeffrey A. Rosenfeld, Benedict Paten, Ryan Layer, Chen-Shan Chin, Fritz J. Sedlazeck, Nancy F. Hansen, Danny E. Miller, Adam M. Phillippy, Karen H. Miga, Rajiv C. McCoy, Megan Y. Dennis, Justin M. Zook, and Michael C. Schatz

Subjects
Multidisciplinary, Genome, General Science & Technology, Genome, Human, Human Genome, Genetic Variation, DNA, Genomics, Reference Standards, Article, Genetics, 2.1 Biological and endogenous factors, Humans, Generic health relevance, Aetiology, Sequence Analysis, Human, Biotechnology
Abstract

Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 million base pairs of sequence, corrects thousands of structural errors, and unlocks the most complex regions of the human genome for clinical and functional study. We show how this reference universally improves read mapping and variant calling for 3202 and 17 globally diverse samples sequenced with short and long reads, respectively. We identify hundreds of thousands of variants per sample in previously unresolved regions, showcasing the promise of the T2T-CHM13 reference for evolutionary and biomedical discovery. Simultaneously, this reference eliminates tens of thousands of spurious variants per sample, including reduction of false positives in 269 medically relevant genes by up to a factor of 12. Because of these improvements in variant discovery coupled with population and functional genomic resources, T2T-CHM13 is positioned to replace GRCh38 as the prevailing reference for human genetics.

Published
2022

34. A genome-wide association study of outcome from traumatic brain injury

Author

Mart Kals, Kevin Kunzmann, Livia Parodi, Farid Radmanesh, Lindsay Wilson, Saef Izzy, Christopher D. Anderson, Ava M. Puccio, David O. Okonkwo, Nancy Temkin, Ewout W. Steyerberg, Murray B. Stein, Geoff T. Manley, Andrew I.R. Maas, Sylvia Richardson, Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, David K. Menon, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan P. Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire DahyotFizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, GuyLoup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J.A. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, LarsOwe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. CastañoLeón, Marc Maegele, Marek Majdan, Alex Manara, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia F.J. Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Paul M. Parizel, JeanFrançois Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan SanchezPorras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Janek Frantzén, Ari Katila, Henna-Rikka Maanpää, Jussi Tallus, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Sonia Jain, Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, John K. Yue, Esther Yuh, Ross Zafonte, Public Health, Cell biology, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J. A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, 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, Maas, Andrew I. R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F. J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, 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, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, 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, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Åkerlund, Cecilia, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Amrein, Krisztina, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Andelic, Nada, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Andreassen, Lasse, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Anke, Audny, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Antoni, Anna, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Audibert, Gérard, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Azouvi, Philippe, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Azzolini, Maria Luisa, Yuh, Esther, Zafonte, Ross, Carroll, Ellen, Chatfield, Doris A., Coles, Jonathan P., Helmy, Adel, Manktelow, Anne, Outtrim, Joanne G., Bartels, Ronald, Takala, Rikka, 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, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, 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, Molecular Neuroscience and Ageing Research (MOLAR), Kals, M, Kunzmann, K, Parodi, L, Radmanesh, F, Wilson, L, Izzy, S, Anderson, C, Puccio, A, Okonkwo, D, Temkin, N, Steyerberg, E, Stein, M, Manley, G, Citerio, G, Genetic Associations In Neurotrauma (GAIN) Consortium, CENTER-TBI, CABI, MGB, TBIcare Studies, TRACK-TBI, „Elsevier Science' grupė, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Complex Disease Genetics, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, and Biostatistics Helsinki

Subjects
Traumatic, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, LOCI, SUSCEPTIBILITY, Traumatic Brain Injury (TBI), Mannose-Binding Lectin, DISEASE, General Biochemistry, Genetics and Molecular Biology, Traumatic brain injury, Consortia, Recovery, Brain Injuries, Traumatic, Genetics, 2.1 Biological and endogenous factors, Humans, Prospective Studies, Aetiology, Traumatic Head and Spine Injury, Outcome, Human Genome, 3112 Neurosciences, Neurosciences, General Medicine, LECTIN, Brain Disorders, Good Health and Well Being, consortia, genome-wide association study, outcome, recovery, traumatic brain injury, Brain Injuries, Genetic Associations In Neurotrauma (GAIN) Consortium, Public Health and Health Services, Human medicine, Transcriptome, Genome-Wide association study
Abstract

EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]

Published
2022
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35. Neurotrauma, COVID and the rationing of intensive care: an ethical approach

Author

Sarah Olson, Jeffrey V. Rosenfeld, and Stephen Honeybul

Subjects
Health Care Rationing, Critical Care, Humans, COVID-19, Surgery, Neurology (clinical), General Medicine, Pandemics
Abstract

The advent of the COVID-19 pandemic with its extreme pressure on resources and intensive care beds has prompted many healthcare providers to consider more fully the potentially futile nature of some treatments and how resources might be better managed. This is especially relevant in the context of neurosurgery which is highly resource dependent in terms of technology, funding, and manpower and it may be difficult to balance fair, equitable and sustainable resource allocation, especially in circumstances where those healthcare resources become limited or completely exhausted. Indeed, it may be necessary to consider limiting the availability of certain neurosurgical services or perhaps reconsider the utility or otherwise of performing procedures that commit very restricted resources, such as intensive care beds, to patients who are arguably receiving limited long-term benefit. In these circumstances, the decision-making paradigm is challenging and there are several ethically disparate viewpoints that need to be reconciled. These include but are not limited to, Futility, Utilitarianism and the Rule of rescue.

Published
2022

36. An initial Glasgow Coma Scale score of 8 or less does not define severe brain injury

Author

Mark Fitzgerald, Terence Tan, Jeffrey V Rosenfeld, Michael Noonan, Jin Tee, Evan Ng, Joseph Mathew, Shane Broderick, Yesul Kim, Christopher Groombridge, Andrew Udy, and Biswadev Mitra

Subjects
Brain Injuries, Traumatic, Emergency Medicine, Humans, Glasgow Coma Scale, Triage, Prognosis
Abstract

The wide-spread use of an initial 'Glasgow Coma Scale (GCS) 8 or less' to define and dichotomise 'severe' from 'mild' or 'moderate' traumatic brain injury (TBI) is an out-dated research heuristic that has become an epidemiological convenience transfixing clinical care. Triaging based on GCS can delay the care of patients who have rapidly evolving injuries. Sole reliance on the initial GCS can therefore provide a false sense of security to caregivers and fail to provide timely care for patients presenting with GCS greater than 8. Nearly 50 years after the development of the GCS - and the resultant misplaced clinical and statistical definitions - TBI remains a heterogeneous entity, in which 'best practice' and 'prognoses' are poorly stratified by GCS alone. There is an urgent need for a paradigm shift towards more effective initial assessment of TBI.

Published
2022

37. Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury

Author

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

Subjects
Stre, business.industry, Traumatic brain injury, Posttraumatic stress disorder, medicine.disease, Stress, cognition, head injury, meuropsychology, posttraumatic stress disorder, stress, Psychiatry and Mental health, Clinical Psychology, Posttraumatic stress, Cognition, Head injury, Neuropsychology, Medicine, Human medicine, Neurology. Diseases of the nervous system, business, RC346-429, Neurocognitive, Clinical psychology
Abstract

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​< ​.001) and lower RAVLT-delayed recall scores (OR ​= ​0.74, 95% CI: 0.61–0.91, p ​= ​.004) after controlling for age, sex, psychiatric history, baseline Glasgow Coma Scale and education. Discussion and conclusion: Poorer performance on cognitive tests assessing task switching and, to a lesser extent, delayed verbal recall is associated with probable PTSD in civilians who have suffered TBI.

Published
2022
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40. Characteristics, management and outcomes of patients with severe traumatic brain injury in Victoria, Australia compared to United Kingdom and Europe

Author

Participants, Belinda J. Gabbe, Shirley Vallance, Eveline J. A. Wiegers, D. James Cooper, Hester F. Lingsma, Andrew I R Maas, Lynnette Murray, Tony Trapani, David K. Menon, Dashiell Gantner, Fiona Lecky, OzENTER-TBI investigators, Ewout W. Steyerberg, Jeffrey V. Rosenfeld, Public Health, CENTER-TBI and OzENTER-TBI investigators and participants, and Collaboration groups: CENTER-TBI and OzENTER-TBI investigators and participants

Subjects
medicine.medical_specialty, Victoria, Traumatic brain injury, Length of hospitalization, Intensive care, Internal medicine, Brain Injuries, Traumatic, medicine, Humans, Glasgow Coma Scale, Prospective Studies, Prospective cohort study, Comparative effectiveness research, General Environmental Science, Outcome comparison, Trauma systems, business.industry, Glasgow Outcome Scale, Outcome measures, medicine.disease, Confidence interval, United Kingdom, Europe, Treatment Outcome, Prognostic model, General Earth and Planetary Sciences, Human medicine, business
Abstract

Injury : international journal of the care of the injured 52(9), 2576-2587 (2021). doi:10.1016/j.injury.2021.04.033, Published by Elsevier Science, Amsterdam [u.a.]

Published
2021
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41. Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study

Author

Susan McLellan, Matthew J Maiden, Jeffrey V. Rosenfeld, Peter Cameron, Belinda J. Gabbe, and D. James Cooper

Subjects
Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, business.industry, Traumatic brain injury, Poison control, Critical Care and Intensive Care Medicine, medicine.disease, Suicide prevention, Occupational safety and health, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, nervous system, 030228 respiratory system, Injury prevention, medicine, 030212 general & internal medicine, business, Critical Care Outcomes, Cohort study
Abstract

Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of the...

Published
2020
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42. Paulus of Aegina and the Historical Origins of Spine Surgery

Author

Jeffrey V. Rosenfeld, Antonio Di Ieva, and Kevin Jang

Subjects
business.industry, Spine, Compendium, Spine trauma, 03 medical and health sciences, 0302 clinical medicine, Spine surgery, Physicians, 030220 oncology & carcinogenesis, Classical antiquity, Humans, Medicine, Orthopedic Procedures, Surgery, Neurology (clinical), business, History, Ancient, 030217 neurology & neurosurgery, Byzantine architecture, Classics
Abstract

Paulus of Aegina (625-690 ad) was the last of the prolific Byzantine physicians. His works consolidated and extended the knowledge of his predecessors, with pioneering efforts to improve the surgical management of spinal injuries. In this article, we review the literature to present an overview of the remarkable evolution of spine surgery throughout classical antiquity. In particular, we discuss the contributions of Paulus to this corpus and explore his classic 7-book anthology, Epitomoe Medicae Libri Septem (Medical Compendium in Seven Books). In reviewing Paulus' legacy, we show the significant milestones in the early development of anatomic and functional knowledge of the spine.

Published
2020
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43. Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial

Author

Yaseen M. Arabi, Jennie Ponsford, Ian Seppelt, Lynnette Murray, Eveline J. A. Wiegers, Peter L. Reilly, Andrew Ross Davies, Rory Wolfe, D. James Cooper, Jeffrey V. Rosenfeld, and Public Health

Subjects
Adult, Male, Decompressive Craniectomy, 030506 rehabilitation, medicine.medical_specialty, Adolescent, Traumatic brain injury, medicine.medical_treatment, Glasgow Outcome Scale, outcomes, Logistic regression, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Intensive care, Brain Injuries, Traumatic, randomized trial, Brain Injuries, Diffuse, Humans, Medicine, intensive care, business.industry, traumatic brain injury, Original Articles, Odds ratio, Prognosis, medicine.disease, Confidence interval, 3. Good health, Clinical trial, Treatment Outcome, Female, Decompressive craniectomy, Neurology (clinical), Intracranial Hypertension, 0305 other medical science, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

Published
2020
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44. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

Author

David Oehme, Tony Goldschlager, Peter Ghosh, Jeffrey V. Rosenfeld, and Graham Jenkin

Subjects
Internal medicine, RC31-1245
Abstract

Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

Published
2015
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45. Low back and leg pain

Author

Jin Wee Tee and Jeffrey V. Rosenfeld

Subjects
medicine.medical_specialty, business.industry, Physical therapy, medicine, Leg pain, business, Low back
Published
2019
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46. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI

Author

Ewout W Steyerberg, Eveline Wiegers, Charlie Sewalt, Andras Buki, Giuseppe Citerio, Véronique De Keyser, Ari Ercole, Kevin Kunzmann, Linda Lanyon, Fiona Lecky, Hester Lingsma, Geoffrey Manley, David Nelson, Wilco Peul, Nino Stocchetti, Nicole von Steinbüchel, Thijs Vande Vyvere, Jan Verheyden, Lindsay Wilson, Andrew I R Maas, David K Menon, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Rafael Badenes, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M Castaño-León, Giorgio Chevallard, Arturo Chieregato, Maryse Cnossen, Mark Coburn, Jonathan Coles, Jamie D Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Helen Dawes, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Simone Dijkland, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Kelly Jones, Mladen Karan, Angelos G Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Steven Laureys, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Angels Lozano, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Davide Mulazzi, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Anna Piippo-Karjalainen, Sébastien Pili Floury, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Stevanovic, Robert Stevens, William Stewart, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Joukje van der Naalt, Gregory Van der Steen, Jeroen T J M van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Roel P J van Wijk, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Paul M Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Daphne Voormolen, Petar Vulekovic, Kevin K W Wang, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Steyerberg, Ew, Wiegers, E, Sewalt, C, Buki, A, Citerio, G, De Keyser, V, Ercole, A, Kunzmann, K, Lanyon, L, Lecky, F, Lingsma, H, Manley, G, Nelson, D, Peul, W, Stocchetti, N, von Steinbuchel, N, Vande, Vyvere T, Verheyden, J, Wilson, L, Maas, Air, Menon, DK (CENTER-TBI Participants and Investigator), Beretta, L, Public Health, Ercole, Ari [0000-0001-8350-8093], Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, CENTER-TBI Participants Investigators, Steyerberg, E, von Steinbüchel, N, Vande Vyvere, T, Maas, A, Menon, D, Ackerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Auslands, K, Azouvi, P, Azzolini, M, Badenes, R, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Castaño-León, A, Chevallard, G, Chieregato, A, Cnossen, M, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dawes, H, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dijkland, S, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubović, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovács, N, Lagares, A, Laureys, S, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lozano, A, Maegele, M, Majdan, M, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mulazzi, D, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Newcombe, V, Nieboer, D, Noirhomme, Q, Nyirádi, J, Oddo, M, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Piippo-Karjalainen, A, Pili Floury, S, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Real, R, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnák, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schäfer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevanovic, A, Stevens, R, Stewart, W, Sundström, N, Synnot, A, Takala, R, Tamás, V, Tamosuitis, T, Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Valeinis, E, Vallance, S, Vámos, Z, van der Naalt, J, Van der Steen, G, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Wijk, R, Vanhaudenhuyse, A, Vargiolu, A, Vega, E, Velt, K, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, Voormolen, D, Vulekovic, P, Wang, K, Williams, G, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Section Neuropsychology, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and RS: FPN NPPP I

Subjects
Male, NEUROTRAUMA EFFECTIVENESS RESEARCH, Glasgow Outcome Scale, ALCOHOL, Cohort Studies, Traumatic brain injury, 0302 clinical medicine, Patient Admission, Quality of life, QUALITY-OF-LIFE, Brain Injuries, Traumatic/classification, Brain Injuries, Traumatic, Longitudinal Studies, Prospective Studies, Registries, Israel, Prospective cohort study, SCALE, Middle Aged, Prognosis, 3. Good health, Europe, Intensive Care Units, Critical Pathways, Female, Cohort study, Adult, medicine.medical_specialty, 03 medical and health sciences, Case mix index, SDG 3 - Good Health and Well-being, medicine, Humans, Glasgow Coma Scale, Traumatic/classification, Psychiatry, Critical Care Outcomes, Diagnosis-Related Groups, Aged, business.industry, MORTALITY, 030208 emergency & critical care medicine, El Niño, Brain Injuries, Human medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13–15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30–66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE

Published
2019
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47. Inadequate Decompressive Craniectomy Following a Wartime Traumatic Brain Injury – An Illustrative Case of Why Size Matters

Author

Jeffrey V. Rosenfeld, Daniel J. Coughlin, Joseph Spinelli, Zachary C Janatpour, Randy S. Bell, and Nicholas S. Szuflita

Subjects
Adult, Male, musculoskeletal diseases, Decompressive Craniectomy, Warfare, medicine.medical_specialty, Bone flap, Traumatic brain injury, medicine.medical_treatment, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Brain Injuries, Traumatic, Humans, Medicine, Retrospective Studies, Decompressive hemicraniectomy, Practice patterns, business.industry, Public Health, Environmental and Occupational Health, 030208 emergency & critical care medicine, General Medicine, Weights and Measures, Penetrating Brain Injury, medicine.disease, Decompressive Craniectomies, Surgery, Treatment Outcome, Decompressive craniectomy, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract

Traumatic brain injury has been called the “signature injury” of the wars in Iraq and Afghanistan, and the management of severe and penetrating brain injury has evolved considerably based on the experiences of military neurosurgeons. Current guidelines recommend that decompressive hemicraniectomy be performed with large, frontotemporoparietal bone flaps, but practice patterns vary markedly. The following case is illustrative of potential clinical courses, complications, and efforts to salvage inadequately-sized decompressive craniectomies performed for combat-related severe and penetrating brain injury. The authors follow this with a review of the current literature pertaining to decompressive craniectomy, and finally provide their recommendations for some of the technical nuances of performing decompressive hemicraniectomy after severe or penetrating brain injury.

Published
2019
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48. A complete reference genome improves analysis of human genetic variation

Author

Chen-Shan Chin, Stephanie M Yan, Skylar Martin, Jeffrey A. Rosenfeld, Alaina Shumate, Arang Rhie, Daniela C. Soto, Sergey Koren, Melanie Kirsche, Joyce V. Lee, Chunlin Xiao, Megan Y. Dennis, Dylan J. Taylor, Ryan M. Layer, Mitchell R. Vollger, Justin M. Zook, Adam M. Phillippy, Melissa M. Meredith, Karen H. Miga, Pavel Avdeyev, Nancy F. Hansen, Benedict Paten, Kishwar Shafin, Danny E. Miller, Jennifer McDaniel, Sergey Aganezov, Rajiv C. McCoy, Michael E.G. Sauria, Nathan D. Olson, Justin Wagner, Samantha Zarate, Fritz J. Sedlazeck, and Michael C. Schatz

Subjects
education.field_of_study, Population, False positive paradox, Human genome, Human genetic variation, Computational biology, Biology, education, Gene, Genome, Human genetics, Reference genome
Abstract

Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 Mbp of sequence, corrects thousands of structural errors, and unlocks the most complex regions of the human genome to clinical and functional study. Here we demonstrate how the new reference universally improves read mapping and variant calling for 3,202 and 17 globally diverse samples sequenced with short and long reads, respectively. We identify hundreds of thousands of novel variants per sample—a new frontier for evolutionary and biomedical discovery. Simultaneously, the new reference eliminates tens of thousands of spurious variants per sample, including up to 12-fold reduction of false positives in 269 medically relevant genes. The vast improvement in variant discovery coupled with population and functional genomic resources position T2T-CHM13 to replace GRCh38 as the prevailing reference for human genetics.One Sentence SummaryThe T2T-CHM13 reference genome universally improves the analysis of human genetic variation.

Published
2021
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49. The complete sequence of a human genome

Author

Sergey Nurk, Sergey Koren, Arang Rhie, Mikko Rautiainen, Andrey V. Bzikadze, Alla Mikheenko, Mitchell R. Vollger, Nicolas Altemose, Lev Uralsky, Ariel Gershman, Sergey Aganezov, Savannah J. Hoyt, Mark Diekhans, Glennis A. Logsdon, Michael Alonge, Stylianos E. Antonarakis, Matthew Borchers, Gerard G. Bouffard, Shelise Y. Brooks, Gina V. Caldas, Haoyu Cheng, Chen-Shan Chin, William Chow, Leonardo G. de Lima, Philip C. Dishuck, Richard Durbin, Tatiana Dvorkina, Ian T. Fiddes, Giulio Formenti, Robert S. Fulton, Arkarachai Fungtammasan, Erik Garrison, Patrick G.S. Grady, Tina A. Graves-Lindsay, Ira M. Hall, Nancy F. Hansen, Gabrielle A. Hartley, Marina Haukness, Kerstin Howe, Michael W. Hunkapiller, Chirag Jain, Miten Jain, Erich D. Jarvis, Peter Kerpedjiev, Melanie Kirsche, Mikhail Kolmogorov, Jonas Korlach, Milinn Kremitzki, Heng Li, Valerie V. Maduro, Tobias Marschall, Ann M. McCartney, Jennifer McDaniel, Danny E. Miller, James C. Mullikin, Eugene W. Myers, Nathan D. Olson, Benedict Paten, Paul Peluso, Pavel A. Pevzner, David Porubsky, Tamara Potapova, Evgeny I. Rogaev, Jeffrey A. Rosenfeld, Steven L. Salzberg, Valerie A. Schneider, Fritz J. Sedlazeck, Kishwar Shafin, Colin J. Shew, Alaina Shumate, Yumi Sims, Arian F. A. Smit, Daniela C. Soto, Ivan Sović, Jessica M. Storer, Aaron Streets, Beth A. Sullivan, Françoise Thibaud-Nissen, James Torrance, Justin Wagner, Brian P. Walenz, Aaron Wenger, Jonathan M. D. Wood, Chunlin Xiao, Stephanie M. Yan, Alice C. Young, Samantha Zarate, Urvashi Surti, Rajiv C. McCoy, Megan Y. Dennis, Ivan A. Alexandrov, Jennifer L. Gerton, Rachel J. O’Neill, Winston Timp, Justin M. Zook, Michael C. Schatz, Evan E. Eichler, Karen H. Miga, and Adam M. Phillippy

Subjects
Complete sequence, Heterochromatin, Genomics, Human genome, Preprint, Computational biology, Biology
Abstract

In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus Chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.

Published
2021
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