Point of view
Evolutionary conceptualization of the injury mechanisms intraumatic brain injury
Conceptualización evolutiva de los mecanismos lesionales en el traumatismo craneoencefálico
a Unidad de Cuidados Neurointensivos, Sanatorio Pasteur, San Fernando del Valle de Catamarca, Argentina
b Unidad de Terapia Intensiva, Hospital San Juan Bautista, San Fernando del Valle de Catamarca, Argentina
c Grupo de Neurocríticos, Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain
Read
3634
Timeswas read the article
1225
Total PDF
2409
Total HTML
Share statistics
array:23 [ "pii" => "S2173572721001685" "issn" => "21735727" "doi" => "10.1016/j.medine.2021.11.009" "estado" => "S300" "fechaPublicacion" => "2022-02-01" "aid" => "1462" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2022;46:90-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S2173572721001697" "issn" => "21735727" "doi" => "10.1016/j.medine.2021.11.010" "estado" => "S300" "fechaPublicacion" => "2022-02-01" "aid" => "1600" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Intensiva. 2022;46:94-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Predictive biomarkers of mortality in critically ill patients with COVID-19" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "94" "paginaFinal" => "96" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biomarcadores predictivos de mortalidad en pacientes críticos con COVID-19" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1564 "Ancho" => 2507 "Tamanyo" => 139569 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curve comparing patients with hs-cTnT levels <12 with respect to patients with hs-cTnT levels ≥ 12 (<span class="elsevierStyleItalic">P</span> = .006).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.M. Sirvent, A. Baro, M. Morales, P. Sebastian, X. Saiz" "autores" => array:5 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Sirvent" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Baro" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Morales" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Sebastian" ] 4 => array:2 [ "nombre" => "X." "apellidos" => "Saiz" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S021056912030334X" "doi" => "10.1016/j.medin.2020.09.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021056912030334X?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572721001697?idApp=WMIE" "url" => "/21735727/0000004600000002/v1_202202020632/S2173572721001697/v1_202202020632/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S217357272100179X" "issn" => "21735727" "doi" => "10.1016/j.medine.2021.11.019" "estado" => "S300" "fechaPublicacion" => "2022-02-01" "aid" => "1704" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2022;46:81-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "81" "paginaFinal" => "89" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Vidal-Cortés, E. Díaz Santos, E. Aguilar Alonso, R. Amezaga Menéndez, M.Á. Ballesteros, M.A. Bodí, M.L. Bordejé Laguna, J. Garnacho Montero, M. García Sánchez, M. López Sánchez, I. Martín-Loeches, A. Ochagavía Calvo, P. Ramírez Galleymore, S. Alcántara Carmona, D. Andaluz Ojeda, O. Badallo Arébalo, H. Barrasa González, M. Borges Sa, Á. Castellanos-Ortega, Á. Estella, R. Ferrer Roca, V. Fraile Gutiérrez, M. Fuset Cabanes, C. Giménez-Esparza Vich, C. González Iglesias, A. Hernández-Tejedor, J.C. Igeño Cano, D. Iglesias Posadilla, J.J. Jiménez Rivera, C. Llanos Jorge, J.A. Llompart-Pou, V. López Camps, C. Lorencio Cárdenas, P. Marcos Neira, M.C. Martín Delgado, M. Martín-Macho González, L. Martín Villén, X. Nuvials Casals, A. Ortiz Suñer, M. Quintana Díaz, P. Rascado Sedes, M. Recuerda Núñez, L. del Río Carbajo, M. Rodríguez Aguirregabiria, A. Rodríguez Oviedo, I. Seijas Betolaza, C. Soriano Cuesta, B. Suberviola Cañas, C. Vera Ching, Á. Vidal González, L. Zapata Fenor, R. Zaragoza Crespo" "autores" => array:52 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Vidal-Cortés" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Díaz Santos" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Aguilar Alonso" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Amezaga Menéndez" ] 4 => array:2 [ "nombre" => "M.Á." "apellidos" => "Ballesteros" ] 5 => array:2 [ "nombre" => "M.A." "apellidos" => "Bodí" ] 6 => array:2 [ "nombre" => "M.L." "apellidos" => "Bordejé Laguna" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Garnacho Montero" ] 8 => array:2 [ "nombre" => "M." "apellidos" => "García Sánchez" ] 9 => array:2 [ "nombre" => "M." "apellidos" => "López Sánchez" ] 10 => array:2 [ "nombre" => "I." "apellidos" => "Martín-Loeches" ] 11 => array:2 [ "nombre" => "A." "apellidos" => "Ochagavía Calvo" ] 12 => array:2 [ "nombre" => "P." "apellidos" => "Ramírez Galleymore" ] 13 => array:2 [ "nombre" => "S." "apellidos" => "Alcántara Carmona" ] 14 => array:2 [ "nombre" => "D." "apellidos" => "Andaluz Ojeda" ] 15 => array:2 [ "nombre" => "O." "apellidos" => "Badallo Arébalo" ] 16 => array:2 [ "nombre" => "H." "apellidos" => "Barrasa González" ] 17 => array:2 [ "nombre" => "M." "apellidos" => "Borges Sa" ] 18 => array:2 [ "nombre" => "Á." "apellidos" => "Castellanos-Ortega" ] 19 => array:2 [ "nombre" => "Á." "apellidos" => "Estella" ] 20 => array:2 [ "nombre" => "R." "apellidos" => "Ferrer Roca" ] 21 => array:2 [ "nombre" => "V." "apellidos" => "Fraile Gutiérrez" ] 22 => array:2 [ "nombre" => "M." "apellidos" => "Fuset Cabanes" ] 23 => array:2 [ "nombre" => "C." "apellidos" => "Giménez-Esparza Vich" ] 24 => array:2 [ "nombre" => "C." "apellidos" => "González Iglesias" ] 25 => array:2 [ "nombre" => "A." "apellidos" => "Hernández-Tejedor" ] 26 => array:2 [ "nombre" => "J.C." "apellidos" => "Igeño Cano" ] 27 => array:2 [ "nombre" => "D." "apellidos" => "Iglesias Posadilla" ] 28 => array:2 [ "nombre" => "J.J." "apellidos" => "Jiménez Rivera" ] 29 => array:2 [ "nombre" => "C." "apellidos" => "Llanos Jorge" ] 30 => array:2 [ "nombre" => "J.A." "apellidos" => "Llompart-Pou" ] 31 => array:2 [ "nombre" => "V." "apellidos" => "López Camps" ] 32 => array:2 [ "nombre" => "C." "apellidos" => "Lorencio Cárdenas" ] 33 => array:2 [ "nombre" => "P." "apellidos" => "Marcos Neira" ] 34 => array:2 [ "nombre" => "M.C." "apellidos" => "Martín Delgado" ] 35 => array:2 [ "nombre" => "M." "apellidos" => "Martín-Macho González" ] 36 => array:2 [ "nombre" => "L." "apellidos" => "Martín Villén" ] 37 => array:2 [ "nombre" => "X." "apellidos" => "Nuvials Casals" ] 38 => array:2 [ "nombre" => "A." "apellidos" => "Ortiz Suñer" ] 39 => array:2 [ "nombre" => "M." "apellidos" => "Quintana Díaz" ] 40 => array:2 [ "nombre" => "P." "apellidos" => "Rascado Sedes" ] 41 => array:2 [ "nombre" => "M." "apellidos" => "Recuerda Núñez" ] 42 => array:2 [ "nombre" => "L." "apellidos" => "del Río Carbajo" ] 43 => array:2 [ "nombre" => "M." "apellidos" => "Rodríguez Aguirregabiria" ] 44 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez Oviedo" ] 45 => array:2 [ "nombre" => "I." "apellidos" => "Seijas Betolaza" ] 46 => array:2 [ "nombre" => "C." "apellidos" => "Soriano Cuesta" ] 47 => array:2 [ "nombre" => "B." "apellidos" => "Suberviola Cañas" ] 48 => array:2 [ "nombre" => "C." "apellidos" => "Vera Ching" ] 49 => array:2 [ "nombre" => "Á." "apellidos" => "Vidal González" ] 50 => array:2 [ "nombre" => "L." "apellidos" => "Zapata Fenor" ] 51 => array:2 [ "nombre" => "R." "apellidos" => "Zaragoza Crespo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210569121001935" "doi" => "10.1016/j.medin.2021.08.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569121001935?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357272100179X?idApp=WMIE" "url" => "/21735727/0000004600000002/v1_202202020632/S217357272100179X/v1_202202020632/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "Evolutionary conceptualization of the injury mechanisms intraumatic brain injury" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "90" "paginaFinal" => "93" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D.A. Godoy, F. Murillo-Cabezas" "autores" => array:2 [ 0 => array:3 [ "nombre" => "D.A." "apellidos" => "Godoy" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "F." "apellidos" => "Murillo-Cabezas" "email" => array:1 [ 0 => "franciscomurillocabezas@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Cuidados Neurointensivos, Sanatorio Pasteur, San Fernando del Valle de Catamarca, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Terapia Intensiva, Hospital San Juan Bautista, San Fernando del Valle de Catamarca, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Grupo de Neurocríticos, Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Conceptualización evolutiva de los mecanismos lesionales en el traumatismo craneoencefálico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1732 "Ancho" => 1674 "Tamanyo" => 120517 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolutionary stages of severe traumatic brain injury. In the acute phase, primary, secondary, and tertiary injuries occur. In the subacute and chronic stage, quaternary injuries occur.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Traumatic brain injury (TBI) is considered a health problem and one of the main causes of morbidity and mortality. Its overall annual incidence rate is 200 people for every 100,000 inhabitants. In developing countries, the prevalence is higher, and it mainly affects young and male adults who have been the victim of a traffic accident or violence. However, in developed countries, this prevalence is lower, and it affects older individuals with sports traumas, falls, or hit-and-runs. In first-world countries with resources and systems of organized care, the predominant causes of death are refractory endocranial hypertension, and late multiple organ dysfunction syndrome while in low-income countries, the predominant causes are avoidable causes such as lesions associated with bleeding and hypoxemia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Pathophysiology of severe traumatic brain injury</span><p id="par0010" class="elsevierStylePara elsevierViewall">Severe TBI is a heterogeneous, dynamic, and progressive condition.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It causes different types of damage due to the external energy applied and absorbed by the cranioencephalic structures (scalp, bones, brain parenchyma, CSF, blood vessels).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The type of injury sustained will basically depend on the location and amount of mechanical load exerted.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> There are different types of mechanical load: hit or direct impact, counter-hit, acceleration and deceleration phenomena, rotation, revolution, angulation, and penetrating injuries with or without expansive waves. The aforementioned mechanisms transmit energy with a static (unmovable) or dynamic (unmovable) skull.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The nature, intensity, and duration of the energy forces described will determine the pattern and spread of the damage sustained.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Brain injuries interact among themselves on an ongoing basis from the very moment of the accident and can be maintained along the different evolutionary stages of TBI including subacute and chronic periods that can be categorized into 4 different types of pathophysiological alterations: primary and secondary injuries<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> whose concepts, etiology, pathophysiology, macro- and microscopic morphology both of primary and secondary injuries have been properly described and are well-known to all of us.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a> In this manuscript we will be introducing new concepts of tertiary and quaternary injuries whose involvement in the prognosis of TBI has not been fully explained to this date (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Tertiary injuries</span><p id="par0015" class="elsevierStylePara elsevierViewall">TBI is an entity with a strong systemic impact. It is essential to understand TBI as an evolutionary process emphasizing the impact it has on mortality and the invalidating sequelae of a primary injury and the development and perpetuation of secondary injuries. However, it is essential to consider within the same “continuum” of multifactorial brain damage, the presence and role of what we call “tertiary injury”, which clearly impacts the pathophysiology of TBI with the same or greater importance compared to primary and secondary injuries.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We describe tertiary injuries as those due to the care and assistance provided to the patient who has sustained a TBI.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> These lesional mechanisms often occur in the context of treatment and prevention of secondary injuries including, though not limited to: (1) complications associated with prolonged stays at the intensive care unit; (2) adverse events associated with drugs or homoderivatives; (3) mechanical ventilation-induced lesions; (4) infections associated, or not, with invasive devices; y (5) multifactorial complications (critical illness myopathy)<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The potentially damaging impact of therapeutic measures implemented for the management of TBI has still not been determined fully. However, this new concept of tertiary injury should not be underestimated. As a matter of fact, it is very useful to assess the possible complications and risk associated with a certain therapy administered, at one time or another, during the comprehensive process of managing a TBI. The Hippocrates premise “primun non nocere” becomes very important here since it would be paradoxical to “hurt while caring”.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Similarly, it is essential to establish protocols and specific prevention measures to control the appearance and progression of this type of lesions.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Quaternary injuries</span><p id="par0035" class="elsevierStylePara elsevierViewall">We describe quaternary injuries as those events that occur during the subacute and chronic period of the TBI. Overall, they cause tissue loss and exacerbate the primary injury. The lesional pathophysiological mechanism of quaternary injuries is still operative even after the acute phase when the process of cellular damage seems to have stopped. Adult reparative neurogenesis appears as a process that tries to counteract or ameliorate the damage.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Experimental studies have confirmed the proliferative capacity of the nervous tissue.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Certain specific lesional biological markers of the central nervous system like the S100β protein and the neurotrophins stimulate endogenous neurogenesis. However, the efficacy and presence of this reparative phenomenon are variable and controversial, and to this date its true impact remains unknown.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">During this period, the following lesional mechanisms are operative:<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0045" class="elsevierStylePara elsevierViewall">Persistence of the inflammatory phenomenon.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0050" class="elsevierStylePara elsevierViewall">Lack of mitigation of the processes of cellular death (necrosis, apoptosis).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0055" class="elsevierStylePara elsevierViewall">Incomplete clean of detritus or debris generated during the lesional process. For example, beta-amyloids, molecular patterns of damage, and myelin compromise the glial function and activate proinflammatory phenotypes. Also, the myelin that is not eliminated causes an autoimmune response capable of triggering demyelination.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0060" class="elsevierStylePara elsevierViewall">Aberrant immune response. For example, different signals originated on the neuronal surface that activate the phagocytosis of these by the glia.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0065" class="elsevierStylePara elsevierViewall">Glial neurotoxicity: on experimental trials it has been observed that the glia releases inflammatory mediators that “corrupt” the astrocytes, which, in turn, trigger neuronal toxicity.</p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">In our own opinion, quaternary injuries have a strong genetic influence, which would explain why 2 individuals with the exact same injury, demographic factors, and comorbidities, among other characteristics, evolve differently and on an individual basis. Some authors have proven that patients who are carriers of the isoform e4 of apolipoprotein E that is involved in cognitive function disorders and further development of Alzheimer’s disease have worse functional results in the long-term.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Similarly, in the future, the quaternary injury could be therapeutically modified. Its most significant and visible targets are the inflammatory phenomenon, the immune response, and the process of reparative neurogenesis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the pathophysiology of TBI, the concepts of tertiary and quaternary injuries arise as new mechanisms of brain injury that should be taken into consideration for a holistic management of care and treatment of TBIs. In the future, the research lines currently ongoing could be shedding light on many of these unsolved challenges.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">None reported.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:3 [ "identificador" => "sec0010" "titulo" => "Pathophysiology of severe traumatic brain injury" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Tertiary injuries" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Quaternary injuries" ] ] ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-12-16" "fechaAceptado" => "2020-02-08" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Godoy DA, Murillo-Cabezas F. Conceptualización evolutiva de los mecanismos lesionales en el traumatismo craneoencefálico. Med Intensiva. 2022;46:90–93.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1732 "Ancho" => 1674 "Tamanyo" => 120517 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolutionary stages of severe traumatic brain injury. In the acute phase, primary, secondary, and tertiary injuries occur. In the subacute and chronic stage, quaternary injuries occur.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CPP, cerebral perfusion pressure; ECH, endocranial hypertension; ICP, intracranial pressure; PtiO2, brain tissue oxygen pressure; SjvO2, jugular venous bulb hemoglobin oxygen saturation; SS, saline solutions; TBI, traumatic brain injury.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Therapeutic measure \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication and reason for implanting the measure \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Potentially associated tertiary injury \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cervical immobilization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stabilization of lesions of the spinal column, prevention of falls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased ICP due to compromised venous drainage at the expense of jugular compression. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Analgesia and sedation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control anxiety, agitation, and pain as contributors to an increased ICP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Propofol: propofol infusion syndrome. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control of the patient-ventilator asynchrony \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dexmedetomidine: bradycardia, hypotension, reduced CPP. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fentanyl: respiratory depression, increased ICP, secondary compromise of cerebral oxygenation. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Midazolam: hypotension, reduced CPP, exacerbation of delirium. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neuromuscular relaxants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control ECH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Masked epileptic seizures, pneumonia, association with critical illness myopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Activation of mechanical ventilation, intense agitation, and protocols for the management of hypothermia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperosmolar solutions (mannitol, hypertonic saline solution) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First level measures to control elevated ICP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mannitol: acute kidney injury, volume overload, electrolytic alterations, hypovolemia, kidney failure, rebound edema cerebral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertonic SS: phlebitis, coagulopathies, hyperchloremia, hypernatremia, acute kidney injury, volume overload, pontine myelinolysis (rare) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperventilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control elevated ICP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Secondary cerebral ischemia (vasoconstriction, high-affinity cerebral hypoxia) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic effects (myocardial, intestinal ischemia) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Barbiturates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Second level measure as “metabolic suppression”, control refractory ECH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myocardial depression, sepsis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ileus and intestinal obstruction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Catheters and intraventricular devices, SjvO2, PtiO2, microdialysis, central, vesical \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multimodal monitorization of the neurocritical patient with TBI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Catheter-related infections (ventriculitis, meningitis, cerebral abscess, pneumonia, urinary tract infections). Bleeding, thrombosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mechanical ventilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Secure airway and control ECH and cerebral hypoxia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mechanical ventilator-induced lung injury \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Barotrauma, biotrauma, volutrauma. Associated pneumonias. Damage to artificial airway \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Transfusion of hemoderivatives \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment of anemic cerebral hypoxia, hemodynamic stabilization, and damage control in acute traumatic bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated/induced pulmonary injury and cardiovascular overload, transfusion. Sepsis. Hemolysis. Transfusion reactions. Transmission of infections. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stay at the intensive care unit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Comprehensive and multidisciplinary management of the patient with TBI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Digestive bleeding, pressure ulcers, venous thromboembolism, exposure to nosocomial germs, critical illness myopathy, neuropathy, and malnutrition \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2822141.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Description of the spectrum of a potential tertiary injury in traumatic brain injury.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing patterns in the epidemiology of traumatic brain injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B. Roozenbeek" 1 => "A.I. Maas" 2 => "D.K. Menon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneurol.2013.22" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Neurol" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "231" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23443846" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Moderate and severe traumatic brain injury in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.I. Maas" 1 => "N. Stocchetti" 2 => "R. Bullock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1474-4422(08)70164-9" "Revista" => array:6 [ "tituloSerie" => "Lancet Neurol" "fecha" => "2008" "volumen" => "7" "paginaInicial" => "728" "paginaFinal" => "741" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18635021" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of brain injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "T.A. Gennarelli" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Emerg Med" "fecha" => "1993" "volumen" => "11 Suppl 1" "paginaInicial" => "5" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8445204" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagramas para interpretar y corregir eventos fisiopatológicos desencadenados tras el traumatismo craneoencefálico grave" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.A. Godoy" 1 => "F. Murillo-Cabezas" 2 => "J.J. Egea-Guerrero" 3 => "J.J. Carmona-Suazo" 4 => "M.A. Muñoz-Sánchez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2014.10.009" "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2015" "volumen" => "39" "paginaInicial" => "445" "paginaFinal" => "447" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25499724" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A conceptual approach to managing severe traumatic brain injury in a time of uncertainly" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.M. Chesnut" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/nyas.12483" "Revista" => array:6 [ "tituloSerie" => "Ann N Y Acad Sci" "fecha" => "2015" "volumen" => "1345" "paginaInicial" => "99" "paginaFinal" => "107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25040396" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Traumatic brain injury: pathophysiology for neurocritical care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K. Kinoshita" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40560-016-0138-3" "Revista" => array:5 [ "tituloSerie" => "J Intensive Care" "fecha" => "2016" "volumen" => "4" "paginaInicial" => "29" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27123305" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of severe traumatic brain injury: a practical approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.A. Godoy" 1 => "A.A. Khan" 2 => "A.M. Rubiano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "editores" => "A.Rabinstein" "titulo" => "Neurological emergencies" "paginaInicial" => "245" "paginaFinal" => "270" "serieFecha" => "2020" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enduring neuroprotective effect of subacute neural stem cell transplantation after penetrating TBI" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.A.Y. Kassi" 1 => "A.K. Mahavadi" 2 => "A. Clavijo" 3 => "D. Caliz" 4 => "S.W. Lee" 5 => "A.I. Ahmed" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fneur.2018.01097" "Revista" => array:5 [ "tituloSerie" => "Front Neurol" "fecha" => "2019" "volumen" => "9" "paginaInicial" => "1097" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30719019" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "F. S100B and Neuron-Specific Enolase as mortality predictors in patients with severe traumatic brain injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Rodríguez-Rodríguez" 1 => "J.J. Egea-Guerrero" 2 => "E. Gordillo-Escobar" 3 => "J. Enamorado-Enamorado" 4 => "C. Hernández-García" 5 => "Z. Ruiz de Azúa-López" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/01616412.2016.1144410" "Revista" => array:6 [ "tituloSerie" => "Neurol Res" "fecha" => "2016" "volumen" => "38" "paginaInicial" => "130" "paginaFinal" => "137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27078699" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between apolipoprotein E and functional outcome after traumatic brain injury: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Li" 1 => "Y. Bao" 2 => "S. He" 3 => "G. Wang" 4 => "Y. Guan" 5 => "D. Ma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MD.0000000000002028" "Revista" => array:5 [ "tituloSerie" => "Medicine" "fecha" => "2015" "volumen" => "94" "paginaInicial" => "e2028" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26579811" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000004600000002/v1_202202020632/S2173572721001685/v1_202202020632/en/main.assets" "Apartado" => array:4 [ "identificador" => "402" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Point of view" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735727/0000004600000002/v1_202202020632/S2173572721001685/v1_202202020632/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572721001685?idApp=WMIE" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 0 | 4 |
| 2024 October | 66 | 45 | 111 |
| 2024 September | 84 | 43 | 127 |
| 2024 August | 105 | 53 | 158 |
| 2024 July | 86 | 36 | 122 |
| 2024 June | 77 | 94 | 171 |
| 2024 May | 76 | 58 | 134 |
| 2024 April | 60 | 39 | 99 |
| 2024 March | 59 | 17 | 76 |
| 2024 February | 72 | 41 | 113 |
| 2024 January | 85 | 41 | 126 |
| 2023 December | 88 | 32 | 120 |
| 2023 November | 85 | 56 | 141 |
| 2023 October | 139 | 24 | 163 |
| 2023 September | 74 | 35 | 109 |
| 2023 August | 54 | 23 | 77 |
| 2023 July | 84 | 32 | 116 |
| 2023 June | 90 | 26 | 116 |
| 2023 May | 80 | 35 | 115 |
| 2023 April | 85 | 23 | 108 |
| 2023 March | 108 | 30 | 138 |
| 2023 February | 60 | 39 | 99 |
| 2023 January | 68 | 32 | 100 |
| 2022 December | 134 | 61 | 195 |
| 2022 November | 110 | 50 | 160 |
| 2022 October | 133 | 74 | 207 |
| 2022 September | 68 | 40 | 108 |
| 2022 August | 54 | 39 | 93 |
| 2022 July | 43 | 40 | 83 |
| 2022 June | 42 | 34 | 76 |
| 2022 May | 35 | 33 | 68 |
| 2022 March | 1 | 0 | 1 |
Show all
