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2. JD-312 – A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression

Author

Jingduo Gao, Haixiang Pei, Fang Lv, Xin Niu, Yu You, Liang He, Shijia Hu, Karan M. Shah, Mingyao Liu, Yihua Chen, Bing Du, Hai Xiong, and Jian Luo

Subjects
Small molecule, MSCs, Osteoarthritis, Cartilage, Regeneration, Repair, Diseases of the musculoskeletal system, RC925-935
Abstract

Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) to enhance cartilage repair and regeneration is a promising strategy to alleviate osteoarthritis (OA) progression. Method: The potency of JD-312 in inducing chondrogenic differentiation of MSCs was assessed and verified. The efficacy of JD-312-treated MSCs was evaluated using a Sprague–Dawley rat DMM model. Additionally, the capacity of JD-312 to successfully recruit bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of OA in vitro was confirmed via intra-articular injection. The repair status of the articular cartilage was analyzed in vivo through histological examination. Result: In this study, we identify JD-312 as a novel non-toxic small molecule that can promote chondrogenic differentiation in human umbilical cord-derived MSCs (hUCMSCs) and human bone marrow MSCS (hBMSCs) in vitro. We also show that transient differentiation of MSCs with JD-312 prior to in vivo administration remarkably improves the regeneration of cartilage and promotes Col2a1 and Acan expression in rat models of DMM, in comparison to kartogenin (KGN) pre-treatment or MSCs alone. Furthermore, direct intra-articular injection of JD-312 in murine model of OA showed reduced loss of articular cartilage and improved pain parameters. Lastly, we identified that the effects of JD-312 are at least in part mediated via upregulation of genes associated with the focal adhesion, PI3K-Akt signaling and the ECM-receptor interaction pathways, and specifically cartilage oligomeric matrix protein (COMP) may play a vital role. Conclusion: Our study demonstrated that JD-312 showed encouraging repair effects for OA in vivo. The translational potential of this article: Together, our findings demonstrate that JD-312 is a promising new therapeutic molecule for cartilage regeneration with clinical potential.

Published
2024
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3. Prospects and Current Challenges of Extracellular Vesicle-Based Biomarkers in Cancer

Author

Samuel R. Lawrence and Karan M. Shah

Subjects
extracellular vesicles, biomarker, liquid biopsy, cancer diagnosis, Biology (General), QH301-705.5
Abstract

Cancer continues to impose a substantial global health burden, particularly among the elderly, where the ongoing global demographic shift towards an ageing population underscores the growing need for early cancer detection. This is essential for enabling personalised cancer care and optimised treatment throughout the disease course to effectively mitigate the increasing societal impact of cancer. Liquid biopsy has emerged as a promising strategy for cancer diagnosis and treatment monitoring, offering a minimally invasive method for the isolation and molecular profiling of circulating tumour-derived components. The expansion of the liquid biopsy approach to include the detection of tumour-derived extracellular vesicles (tdEVs) holds significant therapeutic opportunity. Evidence suggests that tdEVs carry cargo reflecting the contents of their cell-of-origin and are abundant within the blood, exhibiting superior stability compared to non-encapsulated tumour-derived material, such as circulating tumour nucleic acids and proteins. However, despite theoretical promise, several obstacles hinder the translation of extracellular vesicle-based cancer biomarkers into clinical practice. This critical review assesses the current prospects and challenges facing the adoption of tdEV biomarkers in clinical practice, offering insights into future directions and proposing strategies to overcome translational barriers. By addressing these issues, EV-based liquid biopsy approaches could revolutionise cancer diagnostics and management.

Published
2024
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4. GPRC5B protects osteoarthritis by regulation of autophagy signaling

Author

Liang He, Ziwei Xu, Xin Niu, Rong Li, Fanhua Wang, Yu You, Jingduo Gao, Lei Zhao, Karan M. Shah, Jian Fan, Mingyao Liu, and Jian Luo

Subjects
Osteoarthritis, GPRC5B, Cartilage, Chondrocyte, Cartilage anabolism and catabolism, Cartilage regeneration, Therapeutics. Pharmacology, RM1-950
Abstract

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Published
2023
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5. YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522

Author

Darrell Green, Archana Singh, Victoria L. Tippett, Luke Tattersall, Karan M. Shah, Chileleko Siachisumo, Nicole J. Ward, Paul Thomas, Simon Carter, Lee Jeys, Vaiyapuri Sumathi, Iain McNamara, David J. Elliott, Alison Gartland, Tamas Dalmay, and William D. Fraser

Subjects
miRNA, tRF, small RNA, bone cancer, CADD522, Diseases of the musculoskeletal system, RC925-935, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Primary bone cancer (PBC) comprises several subtypes each underpinned by distinctive genetic drivers. This driver diversity produces novel morphological features and clinical behaviour that serendipitously makes PBC an excellent metastasis model. Here, we report that some transfer RNA-derived small RNAs termed tRNA fragments (tRFs) perform as a constitutive tumour suppressor mechanism by blunting a potential pro-metastatic protein-RNA interaction. This mechanism is reduced in PBC progression with a gradual loss of tRNAGlyTCC cleavage into 5′ end tRF-GlyTCC when comparing low-grade, intermediate-grade and high-grade patient tumours. We detected recurrent activation of miR-140 leading to upregulated RUNX2 expression in high-grade patient tumours. Both tRF-GlyTCC and RUNX2 share a sequence motif in their 3′ ends that matches the YBX1 recognition site known to stabilise pro-metastatic mRNAs. Investigating some aspects of this interaction network, gain- and loss-of-function experiments using small RNA mimics and antisense LNAs, respectively, showed that ectopic tRF-GlyTCC reduced RUNX2 expression and dispersed 3D micromass architecture in vitro. iCLIP sequencing revealed YBX1 physical binding to the 3′ UTR of RUNX2. The interaction between YBX1, tRF-GlyTCC and RUNX2 led to the development of the RUNX2 inhibitor CADD522 as a PBC treatment. CADD522 assessment in vitro revealed significant effects on PBC cell behaviour. In xenograft mouse models, CADD522 as a single agent without surgery significantly reduced tumour volume, increased overall and metastasis-free survival and reduced cancer-induced bone disease. Our results provide insight into PBC molecular abnormalities that have led to the identification of new targets and a new therapeutic.

Published
2023
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6. A molecular quantitative trait locus map for osteoarthritis

Author

Julia Steinberg, Lorraine Southam, Theodoros I. Roumeliotis, Matthew J. Clark, Raveen L. Jayasuriya, Diane Swift, Karan M. Shah, Natalie C. Butterfield, Roger A. Brooks, Andrew W. McCaskie, J. H. Duncan Bassett, Graham R. Williams, Jyoti S. Choudhary, J. Mark Wilkinson, and Eleftheria Zeggini

Subjects
Science
Abstract

Understanding the molecular effects of disease variants in relevant tissues is essential to understanding and treating disease. Here, the authors discover expression and protein quantitative trait loci in cartilage and synovium from 115 osteoarthritis patients to pinpoint genes of action and potential drug treatments.

Published
2021
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7. Strategies for Articular Cartilage Repair and Regeneration

Author

Yanxi Liu, Karan M. Shah, and Jian Luo

Subjects
articular cartilage, chondrocyte, microenvironment, regenerative medicine, articular cartilage repair, osteoarthritis, Biotechnology, TP248.13-248.65
Abstract

Articular cartilage is an avascular tissue, with limited ability to repair and self-renew. Defects in articular cartilage can induce debilitating degenerative joint diseases such as osteoarthritis. Currently, clinical treatments have limited ability to repair, for they often result in the formation of mechanically inferior cartilage. In this review, we discuss the factors that affect cartilage homeostasis and function, and describe the emerging regenerative approaches that are informing the future treatment options.

Published
2021
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8. The P2RX7B splice variant modulates osteosarcoma cell behaviour and metastatic properties

Author

Luke Tattersall, Karan M. Shah, Darren L. Lath, Archana Singh, Jennifer M. Down, Elena De Marchi, Alex Williamson, Francesco Di Virgilio, Dominique Heymann, Elena Adinolfi, William D. Fraser, Darrell Green, Michelle A. Lawson, and Alison Gartland

Subjects
ATP, Bone cancer, Osteosarcoma, P2RX7B, Purinergic signalling, Diseases of the musculoskeletal system, RC925-935, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Osteosarcoma (OS) is the most common type of primary bone cancer affecting children and adolescents. OS has a high propensity to spread meaning the disease is often incurable and fatal. There have been no improvements in survival rates for decades. This highlights an urgent need for the development of novel therapeutic strategies. Here, we report in vitro and in vivo data that demonstrates the role of purinergic signalling, specifically, the B isoform of the purinergic receptor P2RX7 (P2RX7B), in OS progression and metastasis. Methods: TE85 and MNNG-HOS OS cells were transfected with P2RX7B. These cell lines were then characterised and assessed for proliferation, cell adhesion, migration and invasion in vitro. We used these cells to perform both paratibial and tail vein injected mouse studies where the primary tumour, bone and lungs were analysed. We used RNA-seq to identify responsive pathways relating to P2RX7B. Results: Our data shows that P2RX7B expression confers a survival advantage in TE85 + P2RX7B and MNNG-HOS + P2RX7B human OS cell lines in vitro that is minimised following treatment with A740003, a specific P2RX7 antagonist. P2RX7B expression reduced cell adhesion and P2RX7B activation promoted invasion and migration in vitro, demonstrating a metastatic phenotype. Using an in vivo OS xenograft model, MNNG-HOS + P2RX7B tumours exhibited cancer-associated ectopic bone formation that was abrogated with A740003 treatment. A pro-metastatic phenotype was further demonstrated in vivo as expression of P2RX7B in primary tumour cells increased the propensity of tumour cells to metastasise to the lungs. RNA-seq identified a novel gene axis, FN1/LOX/PDGFB/IGFBP3/BMP4, downregulated in response to A740003 treatment. Conclusion: Our data illustrates a role for P2RX7B in OS tumour growth, progression and metastasis. We show that P2RX7B is a future therapeutic target in human OS.

Published
2021
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9. Progressive Myoclonic Epilepsy’-like presentation of Cerebrotendinous Xanthomatosis in an Indian Family with A Novel C.646+1G>A Splice Site Mutation

Author

Karan M. Desai, Piyush Kumar, Parthvi S. Ravat, Sangeeta H. Ravat, Neeraj Jain, Shruti Agrawal, and Rahil Ansari

Subjects
Cerebrotendinous Xanthomatosis, Progressive myoclonic epilepsy, Epilepsy, Neurology. Diseases of the nervous system, RC346-429, Neurophysiology and neuropsychology, QP351-495
Abstract

Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal-recessive inborn disorder of bile acid metabolism due to mutations in the CYP27A1 gene. It presents with a diverse range of neurological and non-neurological symptoms. We present a case of CTX with a progressive myoclonic epilepsy (PME) like phenotype and a family history of CTX. The proband had a generalized epilepsy with prominent myoclonus. He also had intellectual decline, ataxia, bipyramidal dysfunction and peripheral neuropathy. The younger sibling had a milder generalized epilepsy without myoclonus along with behavioral issues, ataxia, neuropathy, and prominent tendon xanthomas. Both the siblings had developmental cataracts. MRI Brain of both had dentate hyperintensities with cerebellar atrophy. The proband’s EEG showed severe background slowing with multifocal interictal discharges. Targeted gene of analysis proband revealed a novel homozygous 5′ splice site variation in intron 3 of the CYP27A1 gene. We present a novel phenotype and genotype of CTX presenting with a syndrome of myoclonic epilepsy. This is the first PME-like presentation of CTX to the best of our knowledge. CTX may present with a PME-like clinical phenotype and should be considered as a treatable cause within the differential diagnostic evluation of syndromic epilepsies involving an atypical familial myoclonic epilepsy.

Published
2021
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10. Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis

Author

Julia Steinberg, Graham R. S. Ritchie, Theodoros I. Roumeliotis, Raveen L. Jayasuriya, Matthew J. Clark, Roger A. Brooks, Abbie L. A. Binch, Karan M. Shah, Rachael Coyle, Mercedes Pardo, Christine L. Le Maitre, Yolande F. M. Ramos, Rob G. H. H. Nelissen, Ingrid Meulenbelt, Andrew W. McCaskie, Jyoti S. Choudhary, J. Mark Wilkinson, and Eleftheria Zeggini

Subjects
Medicine, Science
Abstract

Abstract Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes taken from paired intact versus degraded articular cartilage samples across 38 patients undergoing joint replacement surgery (discovery cohort: 12 knee OA, replication cohorts: 17 knee OA, 9 hip OA patients). We combined genome-wide DNA methylation, RNA sequencing, and quantitative proteomics data. We identified 49 genes differentially regulated between intact and degraded cartilage in at least two –omics levels, 16 of which have not previously been implicated in OA progression. Integrated pathway analysis implicated the involvement of extracellular matrix degradation, collagen catabolism and angiogenesis in disease progression. Using independent replication datasets, we showed that the direction of change is consistent for over 90% of differentially expressed genes and differentially methylated CpG probes. AQP1, COL1A1 and CLEC3B were significantly differentially regulated across all three –omics levels, confirming their differential expression in human disease. Through integration of genome-wide methylation, gene and protein expression data in human primary chondrocytes, we identified consistent molecular players in OA progression that replicated across independent datasets and that have translational potential.

Published
2017
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11. Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

Author

Karan M. Shah, Mark J. Dunning, Alison Gartland, and J. Mark Wilkinson

Subjects
hip replacement, osteoblasts, osteoclasts, cobalt, chromium, gene expression, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.

Published
2021
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12. An Adsorption Equilibria Model for Steady State Analysis

Author

Azhar Bin Ismail, Karan M. Sabnani, Li Ang, and Kim Choon Ng

Subjects
Adsorption, Energy distribution function, Statistical rate theory, Universal isotherm model, Technology, Technology (General), T1-995
Abstract

The investigation of adsorption isotherms is a prime factor in the ongoing development of adsorption cycles for a spectrum of advanced, thermally-driven engineering applications, including refrigeration, natural gas storage, and desalination processes. In this work, a novel semi-empirical mathematical model has been derived that significantly enhances the prediction of the steady state uptake in adsorbent surfaces. This model, a combination of classical Langmuir and a novel modern adsorption isotherm equation, allows for a higher degree of regression of both energetically homogenous and heterogeneous adsorbent surfaces compared to several isolated classical and modern isotherm models, and has the ability to regress isotherms for all six types under the IUPAC classification. Using a unified thermodynamic framework, a single asymmetrical energy distribution function (EDF) has also been proposed that directly relates the mathematical model to the adsorption isotherm types. This fits well with the statistical rate theory approach and offers mechanistic insights into adsorption isotherms.

Published
2016
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19. Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study

Author

Akerlund, C, Holst, A, Bhattacharyay, S, Stocchetti, N, Steyerberg, E, Smielewski, P, Menon, D, Ercole, A, Nelson, D, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyotfizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, Dixit, A, Donoghue, E, Dreier, J, Duliere, 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, 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, Kornaropoulos, 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, Castanoleon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, 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, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Retel Helmrich, I, 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, Sanchezporras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Singh, R, Skandsen, T, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Sundstrom, N, 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 Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, 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, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Akerlund C. A. I., Holst A., Bhattacharyay S., Stocchetti N., Steyerberg E., Smielewski P., Menon D. K., Ercole A., Nelson D. W., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., DahyotFizelier C., Dark P., Dawes H., De Keyser V., Degos V., Della Corte F., den Boogert H., Depreitere B., Dixit A., Donoghue E., Dreier J., Duliere G., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos 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. I. R., CastanoLeon A. M., 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. M., Payen J., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Retel Helmrich I., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., Rosand J., Rosenfeld J. V., Rosenlund C., Rosenthal G., Rossaint R., Rossi S., Rueckert D., Rusnak M., Sahuquillo J., Sakowitz O., SanchezPorras R., Sandor J., Schafer N., Schmidt S., Schoechl H., Schoonman G., Schou R. F., Schwendenwein E., Sewalt C., Singh R. D., Skandsen T., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Erp I. A. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vande Vyvere T., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Whitehouse D., Wiegers E., Williams G., Wilson L., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., Zoerle T., Akerlund, C, Holst, A, Bhattacharyay, S, Stocchetti, N, Steyerberg, E, Smielewski, P, Menon, D, Ercole, A, Nelson, D, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyotfizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, Dixit, A, Donoghue, E, Dreier, J, Duliere, 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, 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, Kornaropoulos, 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, Castanoleon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, 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, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Retel Helmrich, I, 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, Sanchezporras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Singh, R, Skandsen, T, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Sundstrom, N, 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 Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, 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, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Akerlund C. A. I., Holst A., Bhattacharyay S., Stocchetti N., Steyerberg E., Smielewski P., Menon D. K., Ercole A., Nelson D. W., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., DahyotFizelier C., Dark P., Dawes H., De Keyser V., Degos V., Della Corte F., den Boogert H., Depreitere B., Dixit A., Donoghue E., Dreier J., Duliere G., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos 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. I. R., CastanoLeon A. M., 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. M., Payen J., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Retel Helmrich I., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., Rosand J., Rosenfeld J. V., Rosenlund C., Rosenthal G., Rossaint R., Rossi S., Rueckert D., Rusnak M., Sahuquillo J., Sakowitz O., SanchezPorras R., Sandor J., Schafer N., Schmidt S., Schoechl H., Schoonman G., Schou R. F., Schwendenwein E., Sewalt C., Singh R. D., Skandsen T., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Erp I. A. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vande Vyvere T., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Whitehouse D., Wiegers E., Williams G., Wilson L., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., and Zoerle T.

Abstract

Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE

Published
2024

20. Prospects and Current Challenges of Extracellular Vesicle-Based Biomarkers in Cancer.

Author

Lawrence, Samuel R. and Shah, Karan M.

Subjects
*EXPANSION of liquids, *EXTRACELLULAR vesicles, *TUMOR markers, *EARLY detection of cancer, *OLDER people
Abstract

Simple Summary: Cancer presents a significant global health challenge, particularly in ageing populations, emphasising the importance of early detection to facilitate personalised care and optimised treatment to improve patient outcomes. Liquid biopsy offers a minimally invasive approach for isolating and profiling circulating tumour-derived components with potential for cancer diagnosis and monitoring. Tumour-derived extracellular vesicles are secreted from cancer cells and harbour cancer-specific cargo with enhanced stability within the blood, indicating their potential utility as a diagnostic biomarker. However, translating extracellular vesicle biomarkers into clinical practice faces significant hurdles. This critical review evaluates the current landscape, challenges, and future directions of tumour-derived extracellular vesicle biomarkers, proposing strategies to overcome translational barriers. The successful integration of a liquid biopsy-based assessment of tumour-derived extracellular vesicles could transform cancer diagnostics and management. Cancer continues to impose a substantial global health burden, particularly among the elderly, where the ongoing global demographic shift towards an ageing population underscores the growing need for early cancer detection. This is essential for enabling personalised cancer care and optimised treatment throughout the disease course to effectively mitigate the increasing societal impact of cancer. Liquid biopsy has emerged as a promising strategy for cancer diagnosis and treatment monitoring, offering a minimally invasive method for the isolation and molecular profiling of circulating tumour-derived components. The expansion of the liquid biopsy approach to include the detection of tumour-derived extracellular vesicles (tdEVs) holds significant therapeutic opportunity. Evidence suggests that tdEVs carry cargo reflecting the contents of their cell-of-origin and are abundant within the blood, exhibiting superior stability compared to non-encapsulated tumour-derived material, such as circulating tumour nucleic acids and proteins. However, despite theoretical promise, several obstacles hinder the translation of extracellular vesicle-based cancer biomarkers into clinical practice. This critical review assesses the current prospects and challenges facing the adoption of tdEV biomarkers in clinical practice, offering insights into future directions and proposing strategies to overcome translational barriers. By addressing these issues, EV-based liquid biopsy approaches could revolutionise cancer diagnostics and management. [ABSTRACT FROM AUTHOR]

Published
2024
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28. A molecular quantitative trait locus map for osteoarthritis

Author

Steinberg, Julia, Southam, Lorraine, Roumeliotis, Theodoros I., Clark, Matthew J., Jayasuriya, Raveen L., Swift, Diane, Shah, Karan M., Butterfield, Natalie C., Brooks, Roger A., McCaskie, Andrew W., Bassett, J. H. Duncan, Williams, Graham R., Choudhary, Jyoti S., Wilkinson, J. Mark, and Zeggini, Eleftheria

Published
2021
Full Text
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30. Prognostic Models for Global Functional Outcome and Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

Author

Mikolic, A, Steyerberg, E, Polinder, S, Wilson, L, Zeldovich, M, von Steinbueche, N, Newcombe, V, Menon, D, van der Naalt, J, Lingsma, H, Maas, A, van Klaveren, D, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Fizelier, C, Dark, P, Dawes, H, 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, Kornaropoulos, 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, Castano Leon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, 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, Pisica, D, Ples, H, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Retel Helmrich, I, 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, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te 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, Van Praag, D, van Veen, E, 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, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Mikolic A., Steyerberg E. W., Polinder S., Wilson L., Zeldovich M., von Steinbueche N., Newcombe V. F. J., Menon D. K., van der Naalt J., Lingsma H. F., Maas A. I. R., van Klaveren D., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., Fizelier C. D., Dark P., Dawes H., De Keyser V., Degos V., Della Corte F., den Boogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos E., Koskinen L. O., 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. M., Maegele M., Majdan M., Manara A., Manley G., Martino C., Marechal H., Mattern J., McMahon C., Melegh B., Menon D., Menovsky T., 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. M., Payen J. F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Retel Helmrich I., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., Rosand J., Rosenfeld J. V., 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. F., Schwendenwein E., Sewalt C., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Stocchetti N., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Te Ao B., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vande Vyvere T., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. W., Wiegers E., Williams G., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., Zoerle T., Mikolic, A, Steyerberg, E, Polinder, S, Wilson, L, Zeldovich, M, von Steinbueche, N, Newcombe, V, Menon, D, van der Naalt, J, Lingsma, H, Maas, A, van Klaveren, D, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Fizelier, C, Dark, P, Dawes, H, 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, Kornaropoulos, 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, Castano Leon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, 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, Pisica, D, Ples, H, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Retel Helmrich, I, 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, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te 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, Van Praag, D, van Veen, E, 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, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Mikolic A., Steyerberg E. W., Polinder S., Wilson L., Zeldovich M., von Steinbueche N., Newcombe V. F. J., Menon D. K., van der Naalt J., Lingsma H. F., Maas A. I. R., van Klaveren D., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., Fizelier C. D., Dark P., Dawes H., De Keyser V., Degos V., Della Corte F., den Boogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos E., Koskinen L. O., 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. M., Maegele M., Majdan M., Manara A., Manley G., Martino C., Marechal H., Mattern J., McMahon C., Melegh B., Menon D., Menovsky T., 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. M., Payen J. F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Retel Helmrich I., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., Rosand J., Rosenfeld J. V., 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. F., Schwendenwein E., Sewalt C., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Stocchetti N., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Te Ao B., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vande Vyvere T., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. W., Wiegers E., Williams G., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., and Zoerle T.

Abstract

After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3–week post-concussion and mental health symptoms. Predictors were selected based on Akaike’s Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better

Published
2023

34. Impact of Household Chemicals on the Ornamental Fish Poecilia sphenops (Valenciennes)

Author

null Azhagu Raj R, null Hemalatha K, null Sudhakani B., null Ari Karan M., null Jeya Murugan E, and null Balachandar M

Subjects
General Computer Science
Abstract

This study examined the impact of various household chemicals, such as Surf excel, hair dye, popular soap, fabric softener, shampoo, and coconut oil, on the ornamental fish Poecilia sphenops (Valenciennes in Cuvier and Valenciennes, 1846). Length-weight relationships, gonadosomatic and hepatosomatic indexes, oxygen consumption, and opercular beat rate were measured to assess the effects of the chemicals (10, 20, and 30 ppm) on the fish. Results showed that at higher concentrations of the chemicals, the fish exhibited increased breathing and signs of distress. The temperature of 28°C was found to be optimum for the growth of P. sphenops, while the lowest growth performance was shown at temperature 30°C. Fish ranged from 37 to 67 mm in total length and 1.10 to 3.10 g in body weight. The female to male sex ratio (4.9:1) deviated significantly from the unity (?²= 214.2, p

Published
2023

37. Review on a prospective study on drug use pattern in pediatric seizures

Author

Marurhi Sandeep J, Suzen Suma K, Sai Karan M, Keerthana Y, and Narayana swamy P

Abstract

Objectives: The objective of this study is to evaluate the drug utilization pattern and to observe possible treatment outcomes. Methods: A Non-experimental prospective observational study has been carried out in tertiary care hospital for a period of six months. A total number of 181 paediatric inpatients of age 1- 14 years with seizures were included and evaluated. The patient case history was collected based on data collection form designed for the study. RESULTS: In our study we observed that female patients are more prevalent. Prevalence of seizures is high among age group 1-5years and low among 11-14 years. Tonic-clonic (51.3%) type of seizures was commonly observed, followed by febrile seizures (19%). Phenytoin is the mostly prescribed drug followed by sodium valproate. Monotherapy is observed mostly. Outcome of the therapy is measured by seizure free period, among which seizure free observed are more 74.1%. The incidence of ADRs in the study group is less (6.6%) and phenytoin is the drug with more number of ADRs. Medication adherence is measured in known epileptic patients (n=67) using MMAS, medium adherence seems to be more (49%). Conclusion: This study strongly highlights that the, Clinical pharmacist has a pivot role in conducting drug utilization studies that helps in comparing the ongoing regimen with the standard treatment guidelines so as to promote the stupendousity of rational use of drugs and to minimize or control the incidence of ADRs.

Published
2022

38. Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study

Author

Howe, E, Zeldovich, M, Andelic, N, von Steinbuechel, N, Fure, S, Borgen, I, Forslund, M, Hellstrom, T, Soberg, H, Sveen, U, Rasmussen, M, Kleffelgaard, I, Tverdal, C, Helseth, E, Lovstad, M, Lu, J, Arango-Lasprilla, J, Tenovuo, O, Azouvi, P, Dawes, H, Roe, C, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, 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, Dellacorte, F, Denboogert, 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, 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, Kornaropoulos, 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, 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, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Helmrich, I, 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, Singh, R, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Ao, B, 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 Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, 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, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Howe E. I., Zeldovich M., Andelic N., von Steinbuechel N., Fure S. C. R., Borgen I. M. H., Forslund M. V., Hellstrom T., Soberg H. L., Sveen U., Rasmussen M., Kleffelgaard I., Tverdal C., Helseth E., Lovstad M., Lu J., Arango-Lasprilla J. C., Tenovuo O., Azouvi P., Dawes H., Roe C., Akerlund C., Amrein K., Andreassen L., Anke A., Antoni A., Audibert G., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., Dahyot-Fizelier C., Dark P., De Keyser V., Degos V., DellaCorte F., denBoogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos E., Koskinen L. -O., 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. I. R., Castano-Leon A. M., 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. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Helmrich I. R., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roise O., Rosand J., Rosenfeld J. V., 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. F., Schwendenwein E., Sewalt C., Singh R. D., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Stocchetti N., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Erp I. A. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vyvere T. V., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Whitehouse D., Wiegers E., Williams G., Wilson L., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., Zoerle T., Howe, E, Zeldovich, M, Andelic, N, von Steinbuechel, N, Fure, S, Borgen, I, Forslund, M, Hellstrom, T, Soberg, H, Sveen, U, Rasmussen, M, Kleffelgaard, I, Tverdal, C, Helseth, E, Lovstad, M, Lu, J, Arango-Lasprilla, J, Tenovuo, O, Azouvi, P, Dawes, H, Roe, C, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, 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, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, 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, Dellacorte, F, Denboogert, 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, 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, Kornaropoulos, 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, 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, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Helmrich, I, 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, Singh, R, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Ao, B, 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 Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, 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, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Howe E. I., Zeldovich M., Andelic N., von Steinbuechel N., Fure S. C. R., Borgen I. M. H., Forslund M. V., Hellstrom T., Soberg H. L., Sveen U., Rasmussen M., Kleffelgaard I., Tverdal C., Helseth E., Lovstad M., Lu J., Arango-Lasprilla J. C., Tenovuo O., Azouvi P., Dawes H., Roe C., Akerlund C., Amrein K., Andreassen L., Anke A., Antoni A., Audibert G., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., Dahyot-Fizelier C., Dark P., De Keyser V., Degos V., DellaCorte F., denBoogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Kornaropoulos E., Koskinen L. -O., 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. I. R., Castano-Leon A. M., 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. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Helmrich I. R., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roise O., Rosand J., Rosenfeld J. V., 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. F., Schwendenwein E., Sewalt C., Singh R. D., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Stocchetti N., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Erp I. A. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., Vyvere T. V., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Whitehouse D., Wiegers E., Williams G., Wilson L., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., and Zoerle T.

Abstract

Background: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Methods: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Results: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma w

Published
2022

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

Author

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, Van Praag D. L. G., Wouters K., Van Den Eede F., Wilson L., Maas A. I. R., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Lozano G. C., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Ceyisakar I., Clusmann H., Coburn M., Coles J., Cooper J. D., 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. D., Depreitere B., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Koraropoulos E., Koskinen L. -O., 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. M., 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. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Ples H., Polinder S., Pomposo I., Posti J. P., 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. V., 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. F., Schwendenwein E., Sewalt C., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Stocchetti N., Sundstrom N., Synnot A., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., Vyvere T. V., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Wiegers E., Williams G., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., Zoerle T., 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, Van Praag D. L. G., Wouters K., Van Den Eede F., Wilson L., Maas A. I. R., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Lozano G. C., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Ceyisakar I., Clusmann H., Coburn M., Coles J., Cooper J. D., 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. D., Depreitere B., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Koraropoulos E., Koskinen L. -O., 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. M., 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. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Ples H., Polinder S., Pomposo I., Posti J. P., 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. V., 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. F., Schwendenwein E., Sewalt C., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Stocchetti N., Sundstrom N., Synnot A., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., 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. T. J. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., Vyvere T. V., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Wiegers E., Williams G., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., and Zoerle T.

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

40. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author

Galimberti, S, Graziano, F, Maas, A, Isernia, G, Lecky, F, Jain, S, Sun, X, Gardner, R, Taylor, S, Markowitz, A, Manley, G, Valsecchi, M, Bellelli, G, Citerio, G, Ackerlund, C, Adams, H, 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, Carbayo Lozano, G, Carbonara, M, Castano-Leon, A, Cavallo, S, Chevallard, G, Chieregato, A, 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, 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, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, Maegele, M, Majdan, M, Manara, A, Marechal, H, Martino, C, Mattern, J, Mcfadyen, C, 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, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rehorcikova, V, Retel Helmrich, I, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, 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, Singh, R, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Unterberg, A, Vajkoczy, P, Valeinis, E, Vallance, S, Vamos, Z, van der Jagt, M, van der Naalt, J, Van der Steen, G, van Dijck, J, van Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, van Wijk, R, Vande Vyvere, T, 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, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Ziverte, A, Zoerle, T, Adeoye, O, Badjatia, N, Barber, J, Bergin, M, Boase, K, Bodien, Y, Chesnut, R, Corrigan, J, Crawford, K, Diaz-Arrastia, R, Dikmen, S, Duhaime, A, Ellenbogen, R, Feeser, V, Ferguson, A, Foreman, B, Gaudette, E, Giacino, J, Gonzalez, L, Gopinath, S, Grandhi, R, Gullapalli, R, Hemphill, C, Hotz, G, Huie, R, Jha, R, Keene, C, Kitagawa, R, Korley, F, Kramer, J, Kreitzer, N, Levin, H, Lindsell, C, Machamer, J, Madden, C, Martin, A, Mcallister, T, Mccrea, M, Merchant, R, Mukherjee, P, Nelson, L, Ngwenya, L, Noel, F, Nolan, A, Okonkwo, D, Palacios, E, Perl, D, Puccio, A, Rabinowitz, M, Robertson, C, Rodgers, R, Rosand, J, Rosenthal, E, Sander, A, Sandsmark, D, Sugar, G, Schneider, A, Schnyer, D, Seabury, S, Sherer, M, Stein, M, Temkin, N, Toga, A, Torres-Espin, A, Valadka, A, Vassar, M, Wang, V, Yue, J, Yuh, E, Zafonte, R, Galimberti S., Graziano F., Maas A. I. R., Isernia G., Lecky F., Jain S., Sun X., Gardner R. C., Taylor S. R., Markowitz A. J., Manley G. T., Valsecchi M. G., Bellelli G., Citerio G., Ackerlund C., Adams H., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., 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. R., Cameron P., Carbayo Lozano G., Carbonara M., Castano-Leon A. M., Cavallo S., Chevallard G., Chieregato A., Clusmann H., Coburn M. S., Coles J., Cooper J. D., 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., den Boogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., 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. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Johnson F., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Koskinen L. -O., Kovacs N., Kowark A., Lagares A., Lanyon L., Laureys S., Ledoux D., Lefering R., Legrand V., Lejeune A., Levi L., Lightfoot R., Lingsma H., Maegele M., Majdan M., Manara A., Marechal H., Martino C., Mattern J., McFadyen C., 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., Oresic M., Ortolano F., Otesile O., Palotie A., Parizel P. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Pisica D., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Rehorcikova V., Retel Helmrich I., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., 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. F., Schwendenwein E., Sewalt C., Singh R. D., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Stevens R., Stewart W., Steyerberg E. W., Stocchetti N., Sundstrom N., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Te Ao B., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., Unterberg A., Vajkoczy P., Valeinis E., Vallance S., Vamos Z., van der Jagt M., van der Naalt J., Van der Steen G., van Dijck J. T. J. M., van Erp I. A., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., van Veen E., van Wijk R., Vande Vyvere T., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Wiegers E., Williams G., Wilson L., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Ziverte A., Zoerle T., Adeoye O., Badjatia N., Barber J., Bergin M., Boase K., Bodien Y., Chesnut R., Corrigan J., Crawford K., Diaz-Arrastia R., Dikmen S., Duhaime A. -C., Ellenbogen R., Feeser V., Ferguson A. R., Foreman B., Gaudette E., Giacino J., Gonzalez L., Gopinath S., Grandhi R., Gullapalli R., Hemphill C., Hotz G., Huie R., Jha R., Keene C. D., Kitagawa R., Korley F., Kramer J., Kreitzer N., Levin H., Lindsell C., Machamer J., Madden C., Martin A., McAllister T., McCrea M., Merchant R., Mukherjee P., Nelson L., Ngwenya L. B., Noel F., Nolan A., Okonkwo D., Palacios E., Perl D., Puccio A., Rabinowitz M., Robertson C., Rodgers R. B., Rosand J., Rosenthal E., Sander A., Sandsmark D., Sugar G., Schneider A., Schnyer D., Seabury S., Sherer M., Stein M., Temkin N., Toga A., Torres-Espin A., Valadka A., Vassar M., Wang K., Wang V., Yue J. 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D., Kitagawa R., Korley F., Kramer J., Kreitzer N., Levin H., Lindsell C., Machamer J., Madden C., Martin A., McAllister T., McCrea M., Merchant R., Mukherjee P., Nelson L., Ngwenya L. B., Noel F., Nolan A., Okonkwo D., Palacios E., Perl D., Puccio A., Rabinowitz M., Robertson C., Rodgers R. B., Rosand J., Rosenthal E., Sander A., Sandsmark D., Sugar G., Schneider A., Schnyer D., Seabury S., Sherer M., Stein M., Temkin N., Toga A., Torres-Espin A., Valadka A., Vassar M., Wang K., Wang V., Yue J. K., Yuh E., and Zafonte R.

Abstract

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07

Published
2022

43. Gprc5b promotes cartilage anabolism and inhibits catabolism by blocking autophagy signaling pathway. Knockout of Gprc5b suppresses cartilage anabolic factors and promotes catabolic factors

Author

He, Liang, primary, Xu, Ziwei, additional, Niu, Xin, additional, Li, Rong, additional, Wang, Fanhua, additional, You, Yu, additional, Gao, Jingduo, additional, Zhao, Lei, additional, Shah, Karan M., additional, Fan, Jian, additional, Liu, Mingyao, additional, and Luo, Jian, additional

Published
2023
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44. Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort study

Author

van Essen, T, van Erp, I, Lingsma, H, Pisică, D, Yue, J, Singh, R, van Dijck, J, Volovici, V, Younsi, A, Kolias, A, Peppel, L, Heijenbrok-Kal, M, Ribbers, G, Menon, D, Hutchinson, P, Manley, G, Depreitere, B, Steyerberg, E, Maas, A, de Ruiter, G, Peul, W, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Castaño-León, A, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, 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, 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, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kompanje, E, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Maegele, M, Majdan, M, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyirádi, J, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rehorčíková, V, Helmrich, I, 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, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Kowark, A, Stevens, R, Stewart, W, Stocchetti, N, Sundström, N, Takala, R, Tamás, 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, Valeinis, E, Vallance, S, Vámos, Z, Van der Jagt, M, van der Naalt, J, Van der Steen, G, Van Hecke, W, van Heugten, C, Van Praag, D, Van Veen, E, van Wijk, R, Vyvere, T, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, von Steinbüchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Zeiler, F, Ziverte, A, Zoerle, T, van Essen, Thomas A., van Erp, Inge A. M., Lingsma, Hester F., Pisică, Dana, Yue, John K., Singh, Ranjit D., van Dijck, Jeroen T. J. M., Volovici, Victor, Younsi, Alexander, Kolias, Angelos, Peppel, Lianne D., Heijenbrok-Kal, Majanka, Ribbers, Gerard M., Menon, David K., Hutchinson, Peter J. A., Manley, Geoffrey T., Depreitere, Bart, Steyerberg, Ewout W., Maas, Andrew I. R., de Ruiter, Godard C. W., Peul, Wilco C., Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubović, 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., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rehorčíková, Veronika, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, 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, Kowark, Ana, Stevens, Robert, Stewart, William, 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, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Jagt, Mathieu, van der Naalt, Joukje, Van der Steen, Gregory, Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Van Veen, Ernest, van Wijk, Roel, Vyvere, Thijs Vande, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Zeiler, Frederick A., Ziverte, Agate, Zoerle, Tommaso, van Essen, T, van Erp, I, Lingsma, H, Pisică, D, Yue, J, Singh, R, van Dijck, J, Volovici, V, Younsi, A, Kolias, A, Peppel, L, Heijenbrok-Kal, M, Ribbers, G, Menon, D, Hutchinson, P, Manley, G, Depreitere, B, Steyerberg, E, Maas, A, de Ruiter, G, Peul, W, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Castaño-León, A, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, 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, 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, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kompanje, E, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Maegele, M, Majdan, M, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyirádi, J, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rehorčíková, V, Helmrich, I, 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, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Kowark, A, Stevens, R, Stewart, W, Stocchetti, N, Sundström, N, Takala, R, Tamás, 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, Valeinis, E, Vallance, S, Vámos, Z, Van der Jagt, M, van der Naalt, J, Van der Steen, G, Van Hecke, W, van Heugten, C, Van Praag, D, Van Veen, E, van Wijk, R, Vyvere, T, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, von Steinbüchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Zeiler, F, Ziverte, A, Zoerle, T, van Essen, Thomas A., van Erp, Inge A. M., Lingsma, Hester F., Pisică, Dana, Yue, John K., Singh, Ranjit D., van Dijck, Jeroen T. J. M., Volovici, Victor, Younsi, Alexander, Kolias, Angelos, Peppel, Lianne D., Heijenbrok-Kal, Majanka, Ribbers, Gerard M., Menon, David K., Hutchinson, Peter J. A., Manley, Geoffrey T., Depreitere, Bart, Steyerberg, Ewout W., Maas, Andrew I. R., de Ruiter, Godard C. W., Peul, Wilco C., Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubović, 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., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rehorčíková, Veronika, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, 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, Kowark, Ana, Stevens, Robert, Stewart, William, 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, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Jagt, Mathieu, van der Naalt, Joukje, Van der Steen, Gregory, Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Van Veen, Ernest, van Wijk, Roel, Vyvere, Thijs Vande, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Zeiler, Frederick A., Ziverte, Agate, and Zoerle, Tommaso

Abstract

Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were

Published
2023

49. A Data-Driven Method for Online Monitoring Tube Wall Thinning Process in Dynamic Noisy Environment

Author

Emily Jianzhong Hao, Jun Long Lim, Jiliang Eugene Phua, Yixin Wang, Chen Zhang, Aayush Madan, Keng Boon Siah, Wenyu Jiang, Ouyang Liu, Kai Wu, Karan M. Sabnani, Shili Xiang, Rebecca Yen-Ni Wong, Yongwei Zhu, and Steven C. H. Hoi

Subjects
Fiber Bragg grating, Control and Systems Engineering, Computer science, Acoustics, Feature extraction, Process (computing), Internal erosion, Tube (fluid conveyance), Electrical and Electronic Engineering, Focus (optics), Signal, Data-driven
Abstract

Tube internal erosion, which corresponds to its wall thinning process, is one of the major safety concerns for tubes. Many sensing technologies have been developed to detect a tube wall thinning process. Among them, fiber Bragg grating (FBG) sensors are the most popular ones due to their precise measurement properties. Most of the current works focus on how to design different types of FBG sensors according to certain physical laws and only test their sensors in controlled laboratory conditions. However, in practice, an industrial system usually suffers from harsh and dynamic environmental conditions, and FBG signals are affected by many unpredictable factors. Consequently, the FBG signals have more fluctuations and are polluted by noises. Hence, the signals no longer directly follow the assumed physical laws and their proposed thinning detection mechanisms no longer work. Targeting at this, this article develops a data-driven model for FBG signal feature extraction and tube wall thickness monitoring using data analytic techniques. In particular, we develop a spatiotemporal model to describe dynamic FBG signals and extract features related to thickness. By taking physical law as guideline, we trace the relationship between the extracted features and the tube wall thickness, based on which we construct an online statistical monitoring scheme for tube wall thinning process. We use both laboratory test and field trial experiment to demonstrate the efficacy and efficiency of the proposed scheme.

Published
2022

50. Sepsis and Total Joint Arthroplasty

Author

Jeffrey B. Stambough, Simon C. Mears, Barnes Cl, Benjamin M. Stronach, and Karan M Patel

Subjects
medicine.medical_specialty, Prosthesis-Related Infections, Joint arthroplasty, business.industry, Arthroplasty, Replacement, Hip, medicine.medical_treatment, Periprosthetic, medicine.disease, Prosthesis, Intensive care unit, law.invention, Sepsis, law, Bacteremia, Intravenous antibiotics, medicine, Humans, Orthopedics and Sports Medicine, In patient, Arthroplasty, Replacement, Knee, Intensive care medicine, business
Abstract

The number of annual total joint arthroplasties (TJA) is increasing. Periprosthetic joint infections (PJI) occur when there is infection involving the prosthesis and surrounding tissue, which has the potential to develop into sepsis if left untreated. Sepsis in patients who have undergone TJA is life threatening and requires urgent treatment. If sepsis is due to PJI, the focus should be on early intravenous antibiotics with aspiration as soon as possible to diagnose the infection. Patients who develop sepsis after surgery for PJI are particularly at high risk for mortality and need to be treated in the intensive care unit.

Published
2022

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