RESUMEN
BACKGROUND: Decreased fretting and corrosion damage at the taper interface of retrieved ceramic-on-polyethylene total hip arthroplasty (THA) implants has been consistently reported; however, resultant fretting corrosion as a function of femoral head size and taper geometry has not been definitively explained. METHODS: Eight cohorts were defined from 157 retrieved THA implants based on femoral head composition (n = 95, zirconia-toughened alumina, ZTA vs n = 62, cobalt-chromium alloy, CoCr), head size (n = 56, 32mm vs n = 101, 36mm), and taper geometry (n = 84, 12/14 vs n = 73, V40). THA implants were evaluated and graded for taper fretting and corrosion. Data were statistically analyzed, including via a 23 factorial modeling. RESULTS: Factorial-based analysis indicated the significant factors related to both resultant (summed) fretting and corrosion damage were head material and taper geometry; head material-taper geometry interaction was also a significant factor in resultant corrosion damage. Lower rates of moderate-to-severe fretting and corrosion damage were exhibited on ZTA heads (ZTA = 13%, CoCr = 38%), smaller heads (32mm = 18%, 36mm = 26%), and 12/14 tapers (12/14 = 13%, V40 = 35%). ZTA+32mm heads demonstrated the lowest rates of moderate-to-severe fretting and corrosion damage (12/14 = 2%, V40 = 7%), whereas CoCr heads with V40 tapers demonstrated the greatest rates of moderate-to-severe damage (32mm = 47%, 36mm = 59%). CONCLUSION: In this series, retrieved implants with ZTA, 32-mm heads paired with 12/14 tapers exhibited lower rates of moderate-to-severe damage. Factorial analysis showed head material, taper geometry, and their interactions were the most significant factors associated with resultant damage grades. Isolating implant features may provide additional information regarding factors leading to fretting and corrosion damage in THA. LEVEL OF EVIDENCE: IV (case series).
Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Artroplastia de Reemplazo de Cadera/efectos adversos , Corrosión , Prótesis de Cadera/efectos adversos , Humanos , Diseño de Prótesis , Falla de PrótesisRESUMEN
BACKGROUND: Ceramic-on-polyethylene (CoP) implants have exhibited lower fretting and corrosion scores than metal-on-polyethylene implants. This study aims at investigating the effect of taper design on taper corrosion and fretting in modular CoP total hip arthroplasty (THA) systems. METHODS: Under an institutional review board--approved protocol, a query of an implant retrieval library from 2002 to 2017 identified 120 retrieved CoP THA systems with zirconia toughened alumina femoral heads. Femoral stem trunnions were visually evaluated and graded for fretting, corrosion, and damage at the taper interface. Medical records were reviewed for patient demographics and implant characteristics. Data were statistically analyzed using Spearman correlation and rank-sum tests with a Dunn's post hoc test, with a significance level of α = 0.05. RESULTS: Four different taper designs were evaluated: 11/13 (n = 18), 12/14 (n = 53), 16/18 (n = 21), and V40 (n = 28). There were no statistically significant demographic differences between taper groups for duration of implantation, laterality, patient age, and patient sex, but patients with 16/18 tapers had a higher body mass index than V40 tapers (P = .012). Duration of implantation had a weak positive correlation with both trunnion fretting (ρ = 0.224, P = .016) and corrosion (ρ = 0.253, P = .006). Summed fretting and corrosion scores were significantly greater on the V40 and 16/18 tapers compared with the 12/14 tapers (all P ≤ .001). CONCLUSION: Taper fretting and corrosion were observed in CoP THA implants and were greatest with V40 and 16/18 tapers and lowest with 12/14 tapers. Differences in taper design characteristics may lead to greater micromotion at the taper-head interface, leading to increased fretting and corrosion.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Cerámica/química , Prótesis de Cadera , Polietileno/química , Diseño de Prótesis , Falla de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Óxido de Aluminio/química , Índice de Masa Corporal , Corrosión , Femenino , Fémur/cirugía , Cabeza Femoral/cirugía , Humanos , Masculino , Persona de Mediana Edad , Reoperación/métodos , Circonio/químicaRESUMEN
Total knee arthroplasty (TKA) has been associated with notable improvements in health-related quality of life of patients with end-stage knee arthritis. Although most patients experience substantial symptomatic relief after TKA, up to 19% of patients are unsatisfied with their outcome. With the dramatic, projected increase in the number of TKAs performed annually, it is crucial to appreciate the various modes of failure associated with this procedure. A comprehensive understanding of the symptomatology and thorough clinical examination aid in identifying the etiology of ongoing knee pain. Ancillary testing including conventional laboratory analyses, imaging studies, and diagnostic injections supplement a thorough history and physical examination. In addition, novel laboratory markers, RNA/DNA-based tests, and novel imaging modalities are emerging as beneficial tools in evaluating patients with a painful TKA. A well-structured, algorithmic approach in the management of these patients is essential in correctly diagnosing the patient and optimizing clinical outcomes.
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Artroplastia de Reemplazo de Rodilla , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Falla de Prótesis/etiología , Diagnóstico Diferencial , Humanos , Examen Físico , Radiografía , Tomógrafos Computarizados por Rayos X , Insuficiencia del TratamientoRESUMEN
BACKGROUND: One proposed strategy to increase the success of irrigation and debridement with implant retention for the treatment of acute periprosthetic joint infection (PJI) is the use of dissolvable antibiotic-impregnated calcium sulfate beads to provide a local depot of antibiotics. The purpose of this study was to evaluate the outcome of such an approach. METHODS: Thirty-two patients with acute hematogenous (18 patients; 1 bilateral) or acute postoperative (14 patients) PJIs who underwent irrigation and debridement with implant retention and addition of antibiotic-impregnated calcium sulfate beads were retrospectively reviewed. PJI followed 27 total knee arthroplasties and 6 total hip arthroplasties. The most common infecting organisms were methicillin-sensitive Staphylococcus aureus (13 of 33) and Streptococcus (9 of 33). The primary outcome parameter was recurrence of infection according to the Musculoskeletal Infection Society criteria. Patients were followed up for a minimum of 3 months or until failure. RESULTS: At a mean of 12.7 months (range, 3-30 months), 16 of the 33 patients failed (48%). Acute hematogenous and acute postoperative PJI had similar failure rates at 47% and 50%, respectively (P = .88). Seven failures required a 2-stage exchange, while 8 patients were treated with chronic antibiotic suppression, being unwilling or unable to undergo further surgical intervention. CONCLUSION: The addition of antibiotic-impregnated calcium sulfate beads does not appear to improve outcomes of irrigation and debridement with implant retention in the setting of acute hematogenous or acute postoperative PJI. Given the short follow-up in this report, this represents a best-case scenario and the overall failure rate may be higher with further follow-up.
Asunto(s)
Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Sulfato de Calcio/química , Desbridamiento/métodos , Infecciones Relacionadas con Prótesis/etiología , Irrigación Terapéutica , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Artritis Infecciosa/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Recurrencia , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Resultado del TratamientoRESUMEN
The goal of this study was to identify supracondylar fracture patterns that were predictive of adverse events and poor outcomes. The study consisted of a retrospective review of patients admitted for surgical treatment of a supracondylar humerus fracture between June 2008 and August 2010. Preoperative radiographs were assessed based on appearance (simple vs oblique vs comminuted), coronal plane displacement (angulated, posterior, posteromedial vs posterolateral), and rotation (rotation vs no rotation). Logistic regression models were used to examine the relationship between fracture pattern and clinical outcome parameters in 373 patients who were followed for 4 weeks or more postoperatively. Outcome parameters included postoperative complications (infection, delayed healing, pin migration, revision surgery), need for physical or occupational therapy, need for postoperative intravenous narcotics, and preoperative nerve injury. Rotation and coronal displacement patterns of the fracture segments were significantly associated with postoperative complications, postoperative need for physical or occupational therapy as a result of residual stiffness, and nerve injury (P<.05). Compared with posteriorly displaced fractures, posterolaterally displaced fractures were associated with significantly greater odds of complications (P=.045), need for physical or occupational therapy (P<.001), and nerve injury (P<.001). Additionally, fractures with rotation were associated with significantly greater odds of complications (P<.001), need for physical or occupational therapy (P<.001), and nerve injury (P<.001) compared with fractures without rotation. Rotation and coronal plane displacement were predictive of complications, need for physical or occupational therapy, and nerve injury, and thus should be considered as potential prognostic variables when evaluating the initial injury pattern.
Asunto(s)
Fracturas del Húmero/cirugía , Complicaciones Posoperatorias/etiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Fracturas del Húmero/diagnóstico por imagen , Lactante , Masculino , Terapia Ocupacional/estadística & datos numéricos , Tempo Operativo , Modalidades de Fisioterapia/estadística & datos numéricos , Cuidados Posoperatorios , Cuidados Preoperatorios , Pronóstico , Radiografía , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Rotación , Resultado del TratamientoRESUMEN
Venous thromboembolism (VTE) prophylaxis after total joint arthroplasty is considered best practice. However, over the past 5 years, there has been considerable debate about the ideal prophylactic regimen or modality. The American Academy of Orthopaedic Surgeons and the American College of Chest Physicians published their most recent clinical practice guidelines about VTE prophylaxis in 2011 and 2012, respectively. In addition, the Surgical Care Improvement Project published their latest recommendations in 2014. In this review, commonly used VTE prophylaxis options and the latest clinical guidelines will be discussed.
Asunto(s)
Anticoagulantes/uso terapéutico , Artroplastia de Reemplazo/efectos adversos , Tromboembolia Venosa/prevención & control , Humanos , Tromboembolia Venosa/etiologíaRESUMEN
Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2-/- mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2-/- mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2-/- mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2-/- genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2-/- mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2-/- had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury.
Asunto(s)
Encéfalo/metabolismo , Traumatismos Craneocerebrales/patología , Receptores de Complemento 3b/deficiencia , Receptores de Complemento 3d/deficiencia , Animales , Astrocitos/metabolismo , Encéfalo/patología , Complemento C3/metabolismo , Traumatismos Craneocerebrales/sangre , Traumatismos Craneocerebrales/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Inmunoglobulina M/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Neuronas/metabolismo , Neuronas/patología , Fosfopiruvato Hidratasa/sangre , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/inmunología , Receptor fas/metabolismoRESUMEN
Total knee arthroplasty represents a well-established and successful procedure; however, ligament incompetence is known to negatively affect surgical outcomes. Here we present an unusual case of early total knee arthroplasty failure secondary to femoral posterior cruciate ligament (PCL) avulsion and associated lateral collateral ligament (LCL) tear, treated successfully with primary PCL repair and LCL reconstruction. For LCL reconstruction, a peroneus longus allograft was passed through an anterior to posterior bony tunnel in the fibular head and docked into a horizontal femoral tunnel. Level of evidence Case report, Level IV.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugía , Osteoartritis de la Rodilla/cirugía , Procedimientos de Cirugía Plástica/métodos , Ligamento Cruzado Posterior/cirugía , Tirantes , Femenino , Humanos , Inestabilidad de la Articulación/etiología , Ligamentos Laterales del Tobillo/lesiones , Persona de Mediana Edad , Ligamento Cruzado Posterior/lesiones , Reoperación , Trasplante HomólogoRESUMEN
BACKGROUND: Novel bone substitutes have challenged the notion of autologous bone grafting as the 'gold standard' for the surgical treatment of fracture nonunions. The present study was designed to test the hypothesis that autologous bone grafting is equivalent to other bone grafting modalities in the management of fracture nonunions of the long bones. METHODS: A retrospective review of patients with fracture nonunions included in two prospective databases was performed at two US level 1 trauma centers from January 1, 1998 (center 1) or January 1, 2004 (center 2), respectively, until December 31, 2010 (n = 574). Of these, 182 patients required adjunctive bone grafting and were stratified into the following cohorts: autograft (n = 105), allograft (n = 38), allograft and autograft combined (n = 16), and recombinant human bone morphogenetic protein-2 (rhBMP-2) with or without adjunctive bone grafting (n = 23). The primary outcome parameter was time to union. Secondary outcome parameters consisted of complication rates and the rate of revision procedures and revision bone grafting. RESULTS: The autograft cohort had a statistically significant shorter time to union (198 ± 172-225 days) compared to allograft (416 ± 290-543 days) and exhibited a trend towards earlier union when compared to allograft/autograft combined (389 ± 159-619 days) or rhBMP-2 (217 ± 158-277 days). Furthermore, the autograft cohort had the lowest rate of surgical revisions (17%) and revision bone grafting (9%), compared to allograft (47% and 32%), allograft/autograft combined (25% and 31%), or rhBMP-2 (27% and 17%). The overall new-onset postoperative infection rate was significantly lower in the autograft group (12.4%), compared to the allograft cohort (26.3%) (P < 0.05). CONCLUSION: Autologous bone grafting appears to represent the bone grafting modality of choice with regard to safety and efficiency in the surgical management of long bone fracture nonunions.
Asunto(s)
Trasplante Óseo/métodos , Fracturas no Consolidadas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína Morfogenética Ósea 2/uso terapéutico , Trasplante Óseo/efectos adversos , Femenino , Fracturas del Fémur/cirugía , Curación de Fractura , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/tratamiento farmacológico , Humanos , Fracturas del Húmero/cirugía , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Radiografía , Proteínas Recombinantes/uso terapéutico , Reoperación/métodos , Estudios Retrospectivos , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.
Asunto(s)
Lesión Pulmonar Aguda/inmunología , Toxina del Cólera/genética , Proteínas del Sistema Complemento/agonistas , Precursores de Proteínas/genética , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Complejo Antígeno-Anticuerpo/farmacología , Toxina del Cólera/agonistas , Toxina del Cólera/antagonistas & inhibidores , Toxina del Cólera/inmunología , Activación de Complemento/efectos de los fármacos , Proteínas del Sistema Complemento/inmunología , Citocinas/biosíntesis , Citocinas/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Haptoglobinas , Inmunoglobulina G/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/patología , Oligopéptidos/farmacología , Péptidos/farmacología , Permeabilidad/efectos de los fármacos , Precursores de Proteínas/agonistas , Precursores de Proteínas/antagonistas & inhibidores , Precursores de Proteínas/inmunología , Transducción de Señal/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/inmunología , Uniones Estrechas/patología , Tráquea/efectos de los fármacos , Tráquea/inmunología , Tráquea/patologíaRESUMEN
During experimental sepsis, excessive generation of the anaphylatoxin C5a results in reduction of the C5a receptor (C5aR) on neutrophils. These events have been shown to result in impaired innate immunity. However, the regulation and fate of C5aR on neutrophils during sepsis are largely unknown. In contrast to 30 healthy volunteers, 60 patients in septic shock presented evidence of complement activation with significantly increased serum levels of C3a, C5a, and C5b-9. In the septic shock group, the corresponding decrease in complement hemolytic activity distinguished survivors from nonsurvivors. Neutrophils from patients in septic shock exhibited decreased C5aR expression, which inversely correlated with serum concentrations of C-reactive protein (CRP) and clinical outcome. In vitro exposure of normal neutrophils to native pentameric CRP led to a dose- and time-dependent loss of C5aR expression on neutrophils, whereas the monomeric form of CRP, as well as various other inflammatory mediators, failed to significantly alter C5aR levels on neutrophils. A circulating form of C5aR (cC5aR) was detected in serum by immunoblotting and a flow-based capture assay, suggestive of an intact C5aR molecule. Levels of cC5aR were significantly enhanced during septic shock, with serum levels directly correlating with lethality. The data suggest that septic shock in humans is associated with extensive complement activation, CRP-dependent loss of C5aR on neutrophils, and appearance of cC5aR in serum, which correlated with a poor outcome. Therefore, cC5aR may represent a new sepsis marker to be considered in tailoring individualized immune-modulating therapy.
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Neutrófilos/inmunología , Neutrófilos/metabolismo , Receptores de Complemento/sangre , Choque Séptico/sangre , Choque Séptico/inmunología , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley , Receptor de Anafilatoxina C5a , Receptores de Complemento/antagonistas & inhibidores , Choque Séptico/mortalidad , SobrevidaAsunto(s)
Proteínas del Sistema Complemento/inmunología , Enfermedades del Sistema Inmune/inmunología , Tuberculosis/inmunología , Animales , Activación de Complemento , Proteínas del Sistema Complemento/genética , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Inmunidad Innata , Pruebas Inmunológicas , Ratones , Ratones Noqueados , Polimorfismo GenéticoRESUMEN
BACKGROUND: In contrast to the established principles of "damage-control orthopedics" for temporary external fixation of long bone or pelvic fractures, the "ideal" timing and modality of fixation of unstable spine fractures in severely injured patients remains controversial. METHODS: A prospective cohort study was designed to evaluate the safety and efficacy of a standardized "spine damage-control" (SDC) protocol for the acute management of unstable thoracic and lumbar spine fractures in severely injured patients. A total of 112 consecutive patients with unstable thoracic or lumbar spine fractures and Injury Severity Score (ISS) of greater than 15 were prospectively enrolled in this study from October 1, 2008, to December 31, 2011. Acute posterior spinal fixation within 24 hours was performed in 42 patients (SDC group), and 70 patients underwent definitive operative spine fixation in a delayed fashion ("delayed surgery"[DS] group). Both cohorts were prospectively analyzed for baseline demographics, length of operative time, amount of intraoperative blood loss, total hospital length of stay, number of ventilator-dependent days, and incidence of early postoperative complications. RESULTS: The mean time to initial spine fixation was significantly decreased in the SDC group (8.9 [1.7] hours vs. 98.7 [22.4] hours, p < 0.01). The SDC cohort had a reduced mean length of operative time (2.4 [0.7] hours vs. 3.9 [1.3] hours), length of hospital stay (14.1 [2.9] days vs. 32.6 [7.8] days), and number of ventilator-dependent days (2.2 [1.5] days vs. 9.1 [2.4] days), compared with the DS group (p < 0.05). Furthermore, the complication rate was decreased in the SDC group with regard to wound complications (2.4% vs. 7.1%), urinary tract infections (4.8% vs. 21.4%), pulmonary complications (14.3% vs. 25.7%), and pressure sores (2.4% vs. 8.6%), compared with the DS cohort (p < 0.05). CONCLUSION: A standardized SDC protocol represents a safe and efficient treatment strategy for severely injured patients with associated unstable thoracic or lumbar fractures. LEVEL OF EVIDENCE: Therapeutic study, level III.
Asunto(s)
Vértebras Lumbares/lesiones , Fracturas de la Columna Vertebral/terapia , Vértebras Torácicas/lesiones , Adulto , Protocolos Clínicos , Fijación de Fractura/métodos , Fijación de Fractura/normas , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Traumatismos de la Médula Espinal/prevención & control , Fracturas de la Columna Vertebral/cirugía , Factores de TiempoRESUMEN
BACKGROUND: The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. METHODS: Male Wistar rats (250 g, 6-10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of "key" inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. RESULTS: Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. CONCLUSION: This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.
Asunto(s)
Inflamación/sangre , Inflamación/etiología , Traumatismo Múltiple/sangre , Traumatismo Múltiple/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Inflamación/metabolismo , Interleucina-6/sangre , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Masculino , Traumatismo Múltiple/complicaciones , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
The role of adaptive immunity in contributing to post-traumatic neuroinflammation and neuropathology after head injury remains largely unexplored. The present study was designed to investigate the pathophysiological sequelae of closed head injury in Rag1(-/-) mice devoid of mature B and T lymphocytes. C57BL/6 wild-type and Rag1(-/-) mice were subjected to experimental closed head injury, using a standardized weight-drop device. Outcome parameters consisted of neurological scoring, quantification of blood-brain barrier (BBB) function, measurement of inflammatory markers and mediators of apoptosis in serum and brain tissue, and assessment of neuronal cell death, astrogliosis, and tissue destruction. There was no difference between wild-type and Rag1(-/-) mice with regard to injury severity and neurological impairment for up to 7 days after head injury. The extent of BBB dysfunction was in a similar range for both groups. Quantification of complement activation fragments in serum revealed significantly attenuated C3a levels in Rag1(-/-) mice compared to wild-type animals. In contrast, the levels of pro- and anti-inflammatory cytokines and pro-apoptotic and anti-apoptotic mediators remained in a similar range for both groups, and the histological analysis of brain sections did not reveal a difference in reactive astrogliosis, tissue destruction, and neuronal cell death in Rag1(-/-) compared to wild-type mice. These findings suggest that adaptive immunity is not of crucial importance for initiating and sustaining the inflammatory neuropathology after closed head injury. The attenuated extent of post-traumatic complement activation seen in Rag1(-/-) mice implies a cross-talk between innate and adaptive immune responses, which requires further investigation in future studies.
Asunto(s)
Inmunidad Adaptativa , Genes RAG-1 , Traumatismos Cerrados de la Cabeza/inmunología , Traumatismos Cerrados de la Cabeza/patología , Animales , Linfocitos B/inmunología , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/fisiopatología , Western Blotting , Activación de Complemento/inmunología , Traumatismos Cerrados de la Cabeza/fisiopatología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/inmunologíaRESUMEN
After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study, we hypothesized that multiple trauma results in immediate activation, consumption, and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality. Therefore, a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score = 30.3 ± 2.9) was performed. After polytrauma, serum was collected as early as possible at the scene, on admission to the emergency room (ER), and 4, 12, 24, 120, and 240 h post-trauma and analyzed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma, and discriminated between lethal and nonlethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin showed a biphasic response after trauma. Key fluid-phase inhibitors of complement, such as C4b-binding protein and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronical rapid activation and dysfunction of complement, suggesting a trauma-induced complementopathy early after injury. These events may participate in the impairment of the innate immune response observed after severe trauma.
Asunto(s)
Traumatismo Múltiple/sangre , Traumatismo Múltiple/inmunología , Complemento C3a/metabolismo , Proteína de Unión al Complemento C4b/metabolismo , Complemento C5a/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Humanos , Lectina de Unión a Manosa/sangre , Traumatismo Múltiple/metabolismo , Estudios ProspectivosRESUMEN
OBJECTIVES: Femoral reaming and intramedullary nailing (IMN) primes polymorphonuclear leukocytes (PMNL) and thereby increases the posttraumatic systemic inflammatory response. Resuscitation with hypertonic saline (HTS) attenuates PMNL activation after trauma-hemorrhage. We hypothesized that preoperative administration of 7.5% HTS attenuates PMNL priming after IMN of unilateral femur shaft fractures compared with 0.9% normal saline. DESIGN: Prospective, randomized, double-blind study. SETTING: Level I trauma center. PATIENTS: Twenty patients between 18 and 80 years of age with an Injury Severity Score less than 25 and a unilateral femur shaft fracture amenable to IMN fixation within 24 hours after injury. INTERVENTION: Patients were allocated to equally sized HTS or normal saline treatment groups (n = 10) before surgery. Solutions were administered in a blinded bag as a single bolus of 4 mL/kg body weight immediately before surgery. Whole blood samples were collected directly before saline application (t0) and at 6, 12, and 24 hours after surgery. MAIN OUTCOME MEASUREMENTS: PMNL surface expression of CD11b and CD62L, as determined by flow cytometry analysis. RESULTS: Demographic characteristics of both treatment groups were comparable. Baseline expression of CD11b and CD62L cell markers was in a similar range in the two cohorts. The expression levels of CD11b were comparable between the two groups throughout the observation time, whereas CD62L levels were significantly higher in the HTS group at 6 and 24 hours after surgery. CONCLUSION AND SIGNIFICANCE: Preoperative infusion of HTS appears to exert an anti-inflammatory effect by attenuating the extent of postoperative PMNL activation after reamed IMN for femoral shaft fractures.
Asunto(s)
Fracturas del Fémur/inmunología , Fracturas del Fémur/cirugía , Inflamación/inmunología , Inflamación/prevención & control , Activación Neutrófila/efectos de los fármacos , Premedicación/métodos , Solución Salina Hipertónica/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Fracturas del Fémur/complicaciones , Fijación Intramedular de Fracturas , Humanos , Inflamación/etiología , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
Asunto(s)
Proteínas del Sistema Complemento/fisiología , Inflamación/inmunología , Heridas y Lesiones/inmunología , Animales , Activación de Complemento/inmunología , Proteínas del Sistema Complemento/inmunología , Humanos , Inmunidad InnataRESUMEN
We report the case of a 28-year old rock climber who survived an "unsurvivable" injury consisting of a vertical free fall from 300 feet onto a solid rock surface. The trauma mechanism and injury kinetics are analyzed, with a particular focus on the relevance of body positioning to ground surface at the time of impact. The role of early patient transfer to a level 1 trauma center, and "damage control" management protocols for avoiding delayed morbidity and mortality in this critically injured patient are discussed.
Asunto(s)
Accidentes por Caídas , Tratamiento de Urgencia , Montañismo/lesiones , Traumatismo Múltiple/terapia , Aceleración , Adulto , Superficie Corporal , Femenino , Humanos , Cinética , Equipos de SeguridadRESUMEN
BACKGROUND: Anorexia nervosa carries the highest mortality rate of any psychiatric disorder. Even the most critically ill anorexic patients may present with normal 'standard' laboratory values, underscoring the need for a new sensitive biomarker. The complement cascade, a major component of innate immunity, represents a driving force in the pathophysiology of multiple inflammatory disorders. The role of complement in anorexia nervosa remains poorly understood. The present study was designed to evaluate the role of complement C3 levels, the extent of complement activation and of complement hemolytic activity in serum, as potential new biomarkers for the severity of anorexia nervosa. PATIENTS AND METHODS: This was a prospective cohort study on 14 patients with severe anorexia nervosa, as defined by a body mass index (BMI) <14 kg/m2. Serum samples were obtained in a biweekly manner until hospital discharge. A total of 17 healthy subjects with normal BMI values served as controls. The serum levels of complement C3, C3a, C5a, sC5b-9, and of the 50% hemolytic complement activity (CH50) were quantified and correlated with the BMIs of patients and control subjects. RESULTS: Serum C3 levels were significantly lower in patients with anorexia nervosa than in controls (median 3.7 (interquartile range (IQR) 2.5-4.9) vs 11.4 (IQR 8.9-13.7, P <0.001). In contrast, complement activation fragments and CH50 levels were not significantly different between the two groups. There was a strong correlation between index C3 levels and BMI (Spearman correlation coefficient = 0.71, P <0.001). CONCLUSIONS: Complement C3 serum levels may represent a sensitive new biomarker for monitoring the severity of disease in anorexia nervosa. The finding from this preliminary pilot study will require further investigation in future prospective large-scale multicenter trials.