P-annotatePDF-v11
INSTRUCTIONS ON THE ANNOTATION OF PDF FILES To view, print and annotate your article you will need Adobe Reader version 9 (or higher). This program is freely available for a whole series of platforms that include PC, Mac, and UNIX and can be downloaded from http://get.adobe.com/reader/. The exact system requirements are given at the Adobe site: http://www.adobe.com/products/reader/tech-specs.html. Note: if you opt to annotate the file with software other than Adobe Reader then please also highlight the appropriate place in the PDF file. PDF ANNOTATIONS Adobe Reader version 9
Adobe Reader version X and XI
When you open the PDF file using Adobe Reader, the Commenting tool bar should be displayed automatically; if not, click on ‘Tools’, select ‘Comment & Markup’, then click on ‘Show Comment & Markup tool bar’ (or ‘Show Commenting bar’ on the Mac). If these options are not available in your Adobe Reader menus then it is possible that your Adobe Acrobat version is lower than 9 or the PDF has not been prepared properly.
To make annotations in the PDF file, open the PDF file using Adobe Reader XI, click on ‘Comment’.
(Mac) PDF ANNOTATIONS (Adobe Reader version 9)
The default for the Commenting tool bar is set to ‘off’ in version 9. To change this setting select ‘Edit | Preferences’, then ‘Documents’ (at left under ‘Categories’), then select the option ‘Never’ for ‘PDF/A View Mode’.
(Changing the default setting, Adobe version 9)
If this option is not available in your Adobe Reader menus then it is possible that your Adobe Acrobat version is lower than XI or the PDF has not been prepared properly.
This opens a task pane and, below that, a list of all Comments in the text. These comments initially show all the changes made by our copyeditor to your file.
HOW TO... Action Insert text
Adobe Reader version 9
Adobe Reader version X and XI
Click the ‘Text Edits’ button on the Commenting tool bar. Click to set the cursor location in the text and simply start typing. The text will appear in a commenting box. You may also cut-and-paste text from another file into the commenting box. Close the box by clicking on ‘x’ in the top right-hand corner.
Click the ‘Insert Text’ icon on the Comment tool bar. Click to set the cursor location in the text and simply start typing. The text will appear in a commenting box. You may also cut-and-paste text from another file into the commenting box. Close
Click the ‘Text Edits’ button on the Commenting tool bar. To highlight the text to be replaced, click and drag the cursor over the text. Then simply type in the replacement text. The replacement text will appear in a commenting box. You may also cut-and-paste text from another file into this box. To replace formatted text (an equation for example) please Attach a file (see below).
on the Click the ‘Replace (Ins)’ icon Comment tool bar. To highlight the text to be replaced, click and drag the cursor over the text. Then simply type in the replacement text. The replacement text will appear in a commenting box. You may also cut-and-paste text from another file into this box. To replace formatted text (an equation for example) please Attach a file (see below).
Click the ‘Text Edits’ button on the Commenting tool bar. Click and drag over the text to be deleted. Then press the delete button on your keyboard. The text to be deleted will then be struck through.
Click the ‘Strikethrough (Del)’ icon on the Comment tool bar. Click and drag over the text to be deleted. Then press the delete button on your keyboard. The text to be deleted will then be struck through.
on the Click on the ‘Highlight’ button Commenting tool bar. Click and drag over the text. To make a comment, double click on the highlighted text and simply start typing.
on the Click on the ‘Highlight Text’ icon Comment tool bar. Click and drag over the text. To make a comment, double click on the highlighted text and simply start typing.
Click on the ‘Attach a File’ button on the Commenting tool bar. Click on the figure, table or formatted text to be replaced. A window will automatically open allowing you to attach the file. To make a comment, go to ‘General’ in the ‘Properties’ window, and then ‘Description’. A graphic will appear in the PDF file indicating the insertion of a file.
Click on the ‘Attach File’ icon on the Comment tool bar. Click on the figure, table or formatted text to be replaced. A window will automatically open allowing you to attach the file. A graphic will appear indicating the insertion of a file.
Click on the ‘Note Tool’ button on the Commenting tool bar. Click to set the location of the note on the document and simply start typing. Do not use this feature to make text edits.
Click on the ‘Add Sticky Note’ icon on the Comment tool bar. Click to set the location of the note on the document and simply start typing. Do not use this feature to make text edits.
the box by clicking on ‘_’ corner.
in the top right-hand
Replace text
Remove text
Highlight text/ make a comment
Attach a file
Leave a note/ comment
HOW TO... Action Review
Adobe Reader version 9 To review your changes, click on the ‘Show’ on the Commenting tool button bar. Choose ‘Show Comments List’. Navigate by clicking on a correction in the list. Alternatively, double click on any mark-up to open the commenting box.
Undo/delete change
To undo any changes made, use the right click button on your mouse (for PCs, Ctrl-Click for the Mac). Alternatively click on ‘Edit’ in the main Adobe menu and then ‘Undo’. You can also delete edits using the right click (Ctrl-click on the Mac) and selecting ‘Delete’.
Adobe Reader version X and XI Your changes will appear automatically in a list below the Comment tool bar. Navigate by clicking on a correction in the list. Alternatively, double click on any mark-up to open the commenting box.
To undo any changes made, use the right click button on your mouse (for PCs, Ctrl-Click for the Mac). Alternatively click on ‘Edit’ in the main Adobe menu and then ‘Undo’. You can also delete edits using the right click (Ctrl-click on the Mac) and selecting ‘Delete’.
SEND YOUR ANNOTATED PDF FILE BACK TO ELSEVIER Save the annotations to your file and return as instructed by Elsevier. Before returning, please ensure you have answered any questions raised on the Query Form and that you have inserted all corrections: later inclusion of any subsequent corrections cannot be guaranteed. FURTHER POINTS x
Any (grey) halftones (photographs, micrographs, etc.) are best viewed on screen, for which they are optimized, and your local printer may not be able to output the greys correctly.
x
If the PDF files contain colour images, and if you do have a local colour printer available, then it will be likely that you will not be able to correctly reproduce the colours on it, as local variations can occur.
x
If you print the PDF file attached, and notice some ‘non-standard’ output, please check if the problem is also present on screen. If the correct printer driver for your printer is not installed on your PC, the printed output will be distorted.
Our reference: WNEU 2586
P-authorquery-v9
AUTHOR QUERY FORM Journal: WNEU
Please e-mail or fax your responses and any corrections to: E-mail:
[email protected]
Article Number: 2586
Fax: 570-409-4520
Dear Author, Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list. Note: if you opt to annotate the file with software other than Adobe Reader then please also highlight the appropriate place in the PDF file. To ensure fast publication of your paper please return your corrections within 48 hours. For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions. Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Location in article
Q1
Query / Remark: Click on the Q link to find the query’s location in text Please insert your reply or correction at the corresponding line in the proof If there are any drug dosages in your article, please verify them and indicate that you have done so by initialing this query Please confirm that given names and surnames have been identified correctly. Please check this box or indicate your approval if you have no corrections to make to the PDF file
Thank you for your assistance.
,
Correspondence 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59
Dabigatran-Associated Spontaneous Acute Cervical Epidural Hematoma LETTER: of dabigatran is rapidly increasing since it was approved T heas anuseeffective alternative to vitamin K antagonists in patients
with atrial fibrillation as it produces a predictable pharmacodynamic effect without the need for coagulation monitoring. (1, 4, 6-8) Many caregivers however are not yet familiar with the use and complications of dabigatran. Although the risk of intracranial hemorrhage is reduced with dabigatran, urgent management of major bleedings is still problematic.
(47.6 seconds). In an attempt to reverse the effects of dabigatran, prothrombin complex concentrate (2000 IU) was administered corresponding to 25 IU/kg as proposed in international guidelines. Urgent posterior cervical laminectomy (C2 C3 C4) with hematoma removal was performed (Figure 2). Bipolar coagulation, a gelatin-thrombin-matrix, and a cellulose matrix were used to obtain adequate local hemostasis. The surgical procedure and the postoperative course were uneventful, with complete neurological recovery obtained by the patient.
We present a 70-year-old male patient with atrial fibrillation on dabigatran therapy (150 mg bid) who presented with acute severe cervical pain quickly followed by tetraplegia, sensory loss, and severe autonomic instability 12 hours after his last dabigatran intake. Urgent computed tomography imaging revealed an acute epidural hematoma at the C2 C3 C4 level (Figure 1). The patient weighed 80 kg. Renal function was normal (estimated glomerular filtration rate: 85 mL/min/1.73 m2), blood platelet count was 143 109/L, and activated partial thromboplastin time was prolonged
Dabigatran competitively, selectively, and reversibly inhibits thrombin/factor IIa (which enables conversion of fibrinogen into fibrin). The effects of dabigatran parallel its time to peak concentration and elimination half-life. Dabigatran has an 80% renal excretion profile, a 35% protein binding, and in patients with a normal renal function, its elimination half-life ranges from 12 to 17 hours. A main issue with dabigatran involves a difficult clinical assessment of the coagulation status and the fact that no reliable reversal agents have been identified (1-8). The future in this regard, however, is promising because recently data on the identification, humanization, and in vitro pharmacology of an antidote for dabigatran (aDabi-Fab) have been published and studies are ongoing (5).
Figure 1. Computed tomographic image of the acute epidural hematoma at the C2 C3 C4 level.
Figure 2. Computed tomographic image after hematoma removal.
WORLD NEUROSURGERY - [-]: -e-, MONTH 2014
www.WORLDNEUROSURGERY.org
COR 5.2.0 DTD WNEU2586_proof 4 November 2014 4:38 pm ce
e1
60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118
CORRESPONDENCE 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135
Best literature recommendations regarding dabigatran include the discontinuation of therapy 1 2 days ahead of invasive procedures in patients with normal kidney function and 3 5 days in patients with impaired renal function. In patients in whom urgent surgery is mandated, no valid reversal treatment exists to date. A number of strategies have been proposed, and preclinical data suggest that prothrombin complex concentrates are a reasonable approach in an attempt to overcome the effect of dabigatran as a factor IIa inhibitor by raising the levels of vitamin K dependent factors to supranormal levels. Hemodialysis may be considered for emergency reversal of dabigatran-induced anticoagulation, although it can be difficult to perform in a hemodynamically unstable patient, as it was the case in our 70-year-old patient who also suffered from autonomic instability (1-8). A consensus regarding the reversal of dabigatran-induced anticoagulation has not been reached yet. In the acute setting, we would recommend the discontinuation of dabigatran, meticulous local hemostatic control, and the use of prothrombin complex concentrate. Caregivers in general and neurologists and neurosurgeons in particular need to be aware of the possible complications of these newer oral anticoagulants. Q1
Sven Bamps1, Tomas Decramer1, Nicolas Vandenbussche2, Peter Verhamme3, Vincent Thijs2, Johan Van Loon1, Tom Theys1 From the Departments of 1Neurosurgery, 2Neurology, and 3Internal Medicine, University Hospital Leuven, Leuven, Belgium To whom correspondence should be addressed: Sven Bamps, M.D. [E-mail:
[email protected]] Published online - -, -; http://dx.doi.org/10.1016/j.wneu.2014.10.012.
e2
www.SCIENCEDIRECT.com
REFERENCES 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139-1151, 2009. 2. Diaz M, Borobia A, Nuñez M, Virto A, Fabra S, Casado M, García-Erce J, Samama C: Use of prothrombin complex concentrates for urgent reversal of dabigatran in the emergency department. Haematologica 98:e143-e144, 2013. 3. Dickneite G, Hoffman M: Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost 111:189-198, 2014. 4. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P: EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 34: 2094-2106, 2013. 5. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T: A specific antidote for dabigatran: functional and structural characterization. Blood 121:3554-3562, 2013. 6. Stangier J, Clemens A: Pharmacology, pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 15(Suppl 1):9S-16S, 2009. 7. Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes D: Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (Dabigatran). Spine 37:E863-E865, 2012. 8. van Ryn J, Stangier J, Haertter S, Liesenfeld K-H, Wienen W, Feuring M, Clemens A: Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103:1116-1127, 2010.
- [-]: -e-, MONTH 2014
COR 5.2.0 DTD WNEU2586_proof 4 November 2014 4:38 pm ce
WORLD NEUROSURGERY
136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152
