Low plasma D-dimer predicts absence of intracranial injury and skull fracture.

BACKGROUND: Intracranial injury (ICI) is a leading cause of morbidity in children; however, the use of computed tomography (CT) to evaluate ICI has significant risks in children. A recent study suggests D-dimer is associated with ICI. We surveyed the performance of plasma D-dimer in ruling out ICI or skull fracture (SF) in children with head trauma. METHODS: In a cross-sectional study in the Emergency Department (ED) at the National Center for Child Health and Development in Tokyo, Japan we reviewed the medical records of all children age 0-16 years brought to the ED with head trauma from January 2010 to July 2013, who underwent CT based on established clinical criteria and had plasma D-dimer measured. We evaluated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of plasma D-dimer, using abnormal findings on CT (ICI, SF) as the criterion standard. We repeated analysis after stratification by age (<2 years, ≥2 years). RESULTS: Among 364 eligible children (112 children <2 year of age), abnormal findings on CT were demonstrated in 33.8% (123/364). With the cut-off set at 0.5 µg/mL, sensitivity was 100.0% (95% confidence interval [CI]: 95.6-100.0%), specificity 34.0% (95%CI: 28.1-40.4%), PPV 43.6% (95%CI: 37.7-49.6%), NPV 100.0% (95%CI: 93.5-100%). After stratification by age (<2 years and ≥2 years), sensitivity (100.0% and 100.0%) and NPV (100.0% and 100.0%) remained high in both age groups. CONCLUSIONS: Low plasma D-dimer (≤0.5 µg/mL) is useful to limit the use of CT in children by excluding traumatic ICI or SF.

Fibrinolysis in trauma patients: wide variability demonstrated by the Lysis Timer.

Hyperfibrinolysis contributes to the pathophysiology of trauma-induced coagulopathy. At present, systematic administration of tranexamic acid (TXA) is recommended in all patients in the early phase of trauma. However, there is some debate regarding whether TXA is beneficial in all trauma patients. A rapid and accurate tool to diagnose hyperfibrinolysis may be useful for tailoring TXA treatment. We conducted a proof-of-concept study of consecutive adult trauma patients. A first blood sample was obtained at the time of pre-hospital care (T1). Patients received 1 g of TXA after T1. A second sample was obtained on arrival at the emergency unit (T2). We examined coagulation, fibrin and fibrinogen formation and degradation. Fibrinolysis was assessed by determining tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor 1 (PAI-1) activity and global fibrinolysis capacity assay using a device developed by Hyphen BioMed: the Lysis Timer (GFC/LT). The study population consisted of 20 patients (42 ± 21 years, index of severity score 32 ± 21). Both coagulation and fibrinolysis were altered at T1. GFC/LT values exhibited hyperfibrinolysis only in five patients. Principal component analysis carried out at T1 showed two main axes of alteration. The major axis was related to coagulation, altered in all patients, while the second axis was related to fibrinolysis. GFC/LT was mainly influenced by PAI-1 activity while fibrin monomers were related to the severity of trauma. At T2, GFC/LT exhibited the marked effect of TXA on clot lysis time. In conclusion, GFC/LT demonstrated huge variation in the fibrinolytic response to trauma.

Plasma D-dimer safely reduces unnecessary CT scans obtained in the evaluation of pediatric head trauma.

PURPOSE: Serum D-dimer has been proposed as a biomarker to aid in the diagnosis of pediatric traumatic brain injury (TBI). We investigated the accuracy of D-dimer in predicting the absence of TBI and evaluated the degree by which D-dimer could limit unnecessary computed tomography scans of the head (CTH). METHODS: Retrospective review of patients with suspected TBI from 2011 to 2013 who underwent evaluation with CTH and quantitative D-dimer. D-dimer levels were compared among patients with clinically-important TBI (ciTBI), TBI, isolated skull fracture and no injury. RESULTS: Of the 663 patients evaluated for suspected TBI, ciTBI was identified in 116 (17.5%), TBI in 77 (11.6%), skull fracture in 61 (9.2%) and no head injury in 409 (61.7%). Patients with no head injury had significantly lower D-dimer values (1531±1791pg/µL) compared to those with skull fracture, TBI and ciTBI (2504±1769, 2870±1633 and 4059±1287pg/µL, respectively, p<0.005). Using a D-dimer value <750pg/µL as a negative screen, no ciTBIs would be missed and 209 CTHs avoided (39.7% of total). CONCLUSION: Low plasma D-dimer predicts the absence of ciTBI for pediatric patient with suspected TBI. Incorporating D-dimer into current diagnostic algorithms may significantly limit the number of unnecessary CTHs performed in this population. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: I.

Neuropeptide Y accelerates post-fracture bone healing by promoting osteogenesis of mesenchymal stem cells.

Fracture repair is a complex yet well orchestrated regenerative process involving numerous signaling and cell types including osteoblasts. Here we showed that NPY, a neurotransmitter with regulatory functions in bone homeostasis, may contribute to the post-fracture bone healing in patients with traumatic brain injury-fracture combined injuries. Our results suggested NPY levels were increased in patients with the combined injuries, accomplished by arising of bone healing markers, such as ALP, OC, PICP and ICTP, than in those with simple fractures, and NPY have direct actions on MSCs to promote their osteogenic differentiation. Our results provided clinical evidences for NPY participating in the bone healing process in a nonhypothalamic manner, most probably by directly promoting osteogenesis of mesenchymal stem cells.

Analysis of S100 calcium binding protein B serum levels in different types of traumatic intracranial lesions.

The objective of this study was to determine whether the type of intracranial traumatic lesions, the number of simultaneous traumatic lesions, and the occurrence of skull and facial bone fractures have an influence on S100 calcium binding protein B (S100B) serum levels. Patients with blunt traumatic brain injury were prospectively enrolled into this cohort study over a period of 13 months. Venous blood samples were obtained prior to emergency cranial CT scan in all patients within 3 h after injury. The patients were then assigned into six groups: 1) concussion, 2) epidural hematoma, 3) subdural hematoma, 4) subarachnoid hemorrhage, 5) brain contusions, and 6) brain edema. The study included 1696 head trauma patients with a mean age of 57.7 ± 25.3 years, and 126 patients (8%) had 182 traumatic lesions on CT. Significant differences in S100B serum levels were found between cerebral edema and the other four bleeding groups: epidural p = 0.0002, subdural p < 0.0001, subarachnoid p = 0.0001, brain contusions p = 0.0003, and concussion p < 0.0001. Significant differences in S100B values between patients with one or two intracranial lesions (p = 0.014) or with three (p < 0.0001) simultaneous intracranial lesions were found. In patients with intracranial traumatic lesions, skull fractures, as well as skull and facial bone fractures occurring together, were identified as significant additional factors for the increase in serum S100B levels (p < 0.0001). Older age was also associated with elevated S100B serum levels (p < 0.0001). Our data show that peak S100B serum levels were found in patients with cerebral edema and brain contusions.

Changes in complete blood count in patients with surgically treated facial fractures.

The purpose of this prospective study was to verify the changes in the preoperative and postoperative complete blood counts of patients with surgically treated facial fractures. Fifty consecutive patients with a mean age of 34 years who presented facial fractures and underwent surgical treatment were included. A complete blood count was performed, comprising the red and white blood cell count (cells/µL), hemoglobin (g/dL), and hematocrit (%) levels. These data were obtained preoperatively and postoperatively during a 6-week period. Statistical analyses were performed using the Kruskal-Wallis and Mann-Whitney tests to identify the possible differences among the groups and among the periods of observation using the Friedman and Wilcoxon matched-pairs signed-ranks tests. The most common location of the fractures was the mandible (42.3%), followed by the zygomatic-orbital (36.5%) and associated locations (21.2%). Leukocytosis was associated with neutrophilia in the immediate postoperative period in all of the groups. There were no values below the reference limits of the values of hemoglobin, hematocrit, and erythrocytes, and no values above the reference limits for the remaining white blood cells, although significant differences among periods were observed in most cells, depending on the type of fracture. The primary findings were leukocytosis associated with neutrophilia, verified in the immediate postoperative period in all of the groups, and the influence of the type of fracture on the significant alterations observed among studied periods on the values of hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, and lymphocytes.

Continuous brain tissue oxygenation monitoring in the management of pediatric stroke.

BACKGROUND: Direct invasive monitoring of brain tissue oxygenation (PbtO(2)) has been routinely utilized to predict cerebral ischemia and to prevent secondary injury in patients with traumatic brain injury (TBI) and vasospasm secondary to subarachnoid hemorrhage (SAH). The safety and utility of these devices in the pediatric population have been examined in a few small studies. No studies, however, have examined the use of PbtO(2) monitoring in stroke patients. METHODS: Retrospective chart review of the first two consecutive, critically ill pediatric patients in the pediatric intensive care unit requiring brain tissue oxygen monitoring for newly diagnosed cerebral ischemia. ICP, CPP, PbtO(2), SaO(2), BP, and RR were all continually monitored during their care and were retrospectively collected and reviewed. RESULTS: We present two pediatric stroke patients managed in a critical care setting with PbtO(2) monitoring in addition to ICP, MAP, CPP, and SaO(2). Both patients had multiple events of low brain tissue oxygen (PbtO(2) <20 torr), independent of abnormal values in other monitoring parameters, which required physician intervention. No new ischemic damage occurred after PbtO(2) monitoring began in either patient. CONCLUSIONS: There is currently inadequate data to support the application of PbtO(2) monitoring in children with stroke to prevent progressive ischemia and to improve outcome. However, the positive results for these two patients support the need for further study in this area.

Serum-mediated osteogenic effect in traumatic brain-injured patients.

BACKGROUND: Patients with a traumatic brain injury (TBI) and bone fractures often show an enhanced fracture healing, as well as an increased incidence of heterotopic ossifications (HO). It has been suggested that unknown osteoinductive factors may be released by the injured brain into the systemic blood circulation and act peripherally on the affected tissues. The aim of this study was to investigate whether serum from TBI patients is osteoinductive. METHODS: Sixty-one consecutive patients were classified into four groups: TBI and long-bone fracture (group I, n = 12), isolated severe TBI (group II, n = 21), isolated long-bone fracture (group III, n = 19) and controls (group IV, n = 9). Blood samples were collected at 6, 24, 72 and 168 h post-injury. The osteogenic potential was determined by measuring the in vitro proliferation rate of the human fetal osteoblastic cell line hFOB1.19, and primary human osteoblasts. Additionally, serum induced osteoblastic differentiation was assessed by measuring the mRNA expression of specific osteoblastic markers, including alkaline phosphatase, runt-related transcription factor 2, cathepsin K and serine protease 7. RESULTS: The sera of group I induced a higher mean proliferation rate of primary human osteoblasts at all time points of sampling than group III (P < 0.05). Group I had a higher mean proliferation rate of hFOB1.19 cells than all other groups at 6, 24 and 72 h post-injury (P < 0.05). The expression of alkaline phosphatase, cathepsin K and runt-related transcription factor 2 mRNA was increased in group I compared with group III and serine protease 7 was exclusively expressed in group I. CONCLUSION: The study results strongly support a humoral mechanism in enhanced fracture healing and the induction of HO after TBI. Increased proliferation of osteoblastic cells and an accelerated differentiation of osteoprogenitor cells may be responsible for increased osteogenesis in TBI.

Elevated blood lead resulting from maxillofacial gunshot injuries with lead ingestion.

PURPOSE: The purpose of this study was to identify the contribution of ingested lead particles to elevated blood lead concentrations in victims of gunshot injury to the maxillofacial region. PATIENTS AND METHODS: As part of a larger study of the effects of retained lead bullets on blood lead, a retrospective review of study findings was completed on 5 of 8 patients who sustained injuries to the maxillofacial region. These 5 patients were recruited into the larger study within 11 days of injury and showed a penetration path for the projectile that engaged the upper aerodigestive tract. All subjects were recruited from patients presenting for care of their gunshot injuries to a large inner-city trauma center with a retained bullet resulting from a gunshot injury. An initial blood lead level was measured for all recruited patients and repeated 1 to 17 weeks later. Medical history was taken along with a screening and risk factor questionnaire to determine other potential or actual sources (occupational/recreational) of lead exposure. (109)Cd K-shell x-ray fluorescence determinations of bone lead were completed to determine past lead exposure not revealed by medical history and risk factor questionnaire. Radiographs taken of the abdomen and chest, required as a part of the patient's hospital care, were retrospectively reviewed for signs of metallic fragments along the aerodigestive tract. RESULTS: All 5 patients retained multiple lead pellets or fragments at the site of injury, sustained fractures of the facial bones, and showed increases in blood lead. Three of the 5 study subjects who sustained maxillofacial gunshot injuries involving the mouth, nose, or throat region showed metallic densities along the gastrointestinal tract indicative of ingested bullet fragments. Each patient with ingested bullet fragments showed rapid elevation of blood lead exceeding 25 microg/dL and sustained increases well beyond the time when all ingested fragments were eliminated. A 3-year follow-up on these 3 patients showed significantly sustained elevation of blood lead but less than that observed during the initial 6 months after injury. None of the 5 study subjects showed any evidence of metallic foreign bodies within the tracheobronchial regions indicative of aspiration. CONCLUSION: Ingestion of lead fragments can result from gunshot injuries to the maxillofacial region and may substantially contribute to a rapid increase in blood lead level. Prompt diagnosis and elimination of ingested lead fragments are essential steps necessary to prevent lead being absorbed from the gastrointestinal tract. Increased blood lead in victims after gunshot injuries must be fully evaluated for all potential sources, including recent environmental exposure, absorption of lead from any remaining bullets in body tissues, and the possibility of mobilization of lead from long-term body stores such as bone.

Head injury monitoring using cerebral microdialysis and Paratrend multiparameter sensors.

INTRODUCTION: Following head injury complex pathophysiological changes occur in brain metabolism. The objective of the study was to monitor brain metabolism using the Paratrend multiparameter sensor and microdialysis catheters. PATIENTS, MATERIAL AND METHODS: Following approval by the Local Ethics Committee and consent from the relatives, patients with severe head injury were studied using a triple bolt inserted into the frontal region, transmitting an intracranial pressure monitor, microdialysis (10 mm or 30 mm membrane; glucose, lactate, pyruvate, glutamate) catheter and Paratrend multiparameter (oxygen, carbon dioxide, pH and temperature) sensor. A Paratrend sensor was also inserted into the femoral artery for continuous blood gas analysis. RESULTS: 21 patients were studied with cerebral microdialysis for a total of 91 monitoring days (range 19 hours to 12 days). Of these, 14 patients were also studied with cerebral and arterial Paratrend sensors. The mean (+/- 95% confidence intervals) arterial and cerebral oxygen levels were 123 +/- 10.9 mmHg and 27.9 +/- 5.71 mmHg respectively. The arterial and cerebral carbon dioxide levels were 34.3 +/- 2.35 mmHg and 45.3 +/- 3.07 mmHg respectively. Episodes of systemic hypoxia and hypotension resulting in falls in cerebral oxygen and rises in cerebral carbon dioxide were rapidly detected by the arterial and cerebral Paratrend sensors. Systemic pyrexia was reflected in the brain with the cerebral Paratrend sensor reading 0.17 degree C (mean) higher than the arterial sensor. Elevations of cerebral glucose were detected, but the overall cerebral glucose was low (mean 1.57 +/- 0.53 mM 10 mm membrane; mean 1.95 +/- 0.68 mM 30 mm membrane) with periods of undetectable glucose in 6 patients. Lactate concentrations (mean 5.08 +/- 0.73 mM 10 mm membrane; mean 8.27 +/- 1.31 mM 30 mm membrane) were higher than glucose concentrations in all patients. The lactate/pyruvate ratio was 32.1 +/- 5.16 for the 10 mm membrane and 30.6 +/- 2.17 for the 30 mm membrane. Glutamate concentrations varied between patients (mean 15.0 +/- 10.5 microM 10 mm membrane; mean 28.8 +/- 17.8 microM 30 mm membrane). CONCLUSION: The combination of microdialysis catheters and Paratrend sensors enabling the monitoring of substrate delivery and brain metabolism, and the detection of secondary metabolic insults has the potential to assist in the management of head-injured patients.

[Changes in hemocoagulation in children with cranio-cerebral trauma]. / Zmeny hemokoagulace u detí s kraniocerebrálním traumatem.

The authors monitored in children with craniocerebral injuries hospitalized in their department in the course of the more than one-year existence of the child ARO ward in addition to other vital parameters also changes of the haemocoagulation system. They describe the majority of commonly observed abnormalities as "latent consumption coagulopathy", where laboratory findings are not associated with clinical signs of coagulopathy. On the other end of the spectrum of coagulopathies after head injuries is the unit of disseminated consumption coagulopathy which is generally evaluated as a secondary phenomenon or as an intermediary mechanism of the disease which complicates various pathological conditions incl. craniocerebral injuries. The authors discuss the pathophysiology, diagnostic possibilities and their experience with the treatment of the mentioned disorders.

[The DIC syndrome in severe trauma to the skull and brain]. / DVS-sindrom pri tiazheloi travme cherepa i golovnogo mozga.

The article is based on the analysis of the hemocoagulation system in 205 patients (91 with contusion of the brain without compression and 114 with compression). Evaluation of the clinical signs, hemocoagulation disorders, and pathophysiological data revealed 89 (43.4%) cases of the disseminated intravascular coagulation syndrome. Besides other factors, exhaustion of the functioning of the anticoagulation ability of the blood in increased functioning of the coagulation system promoted the development of the syndrome. The syndrome was encountered mostly in the mesencephalobulbar (in 33 among 42 cases) and the diencephalic (in 17 of 37 cases) forms of brain lesions and in subdural hematomas (in 33 among 47 cases). Total mortality was 30.2% (62 among 205), disseminated intravascular coagulation syndrome mortality was 55% (49 among 89 cases).

Acute phase protein levels as an index of severity of physical injury.

Inflammation resulting from any form of tissue injury causes an increase in plasma concentration of a number of liver-derived proteins (the acute phase reactant proteins), the measurement of which provides an indication of the magnitude of the inflammatory response. C reactive protein (CRP) is an example of an acute phase protein. Although concentrations increase particularly dramatically in response to inflammation and reflect the degree of ongoing tissue damage, this method has yet to be used to assess severity of injury in traumatology and forensic medicine. The rate at which the acute phase protein response occurred after injury was therefore explored in a series of 16 patients with maxillofacial skeletal injuries and in a series of 22 age- and sex-matched control patients. Increases in the plasma concentration of CRP were not detected until 6-12 h after injury and peaked at 48-72 h. Concentration of CRP was less than 10 mgm/l in all control patients. There was significant relation between peak levels and Abbreviated Injury Scale and Injury Severity scores. Results suggest that this method of assessing the severity of traumatic injury deserves further investigation and may be of use clinically, medico-legally and in relation to compensation awards.

[Role of kinins in the pathogenesis of craniocerebral injury and the validation of corrective antiproteolytic therapy]. / Rol' kininov v patogeneze cherepno-mozgovoi travmy i obosnovanie korrigiruiushchei antiproteoliticheskoi terapii.

The role of the kinin system in the development of extra- and intracerebral complications in the acute period of severe craniocerebral trauma was studied from complex clinical and biochemical examination. The authors substantiate the expediency of applying corrective antiproteolytic therapy, in which case the predominant trend of its action--inhibition of kinin production in the vascular bed or on the tissue level--must be taken into account. The time, duration, and methods of Contrykal administration were developed.

Coagulation disorders following acute head injury.

Coagulation disorders following acute head injury were investigated in 100 patients: 81 patients survived and 19 patients died. Disseminated intravascular coagulation (DIC) was seen in 24%, and occurred most frequently in acute subdural haematoma, followed by contusional haematoma and contusion. Mortality rate of the patients with DIC was 58%. Level of serum fibrin-fibrinogen degradation product (FDP) was correlated with the amount of damaged tissue. The factors which influenced the prognosis for life were evaluated by multivariate analysis: in 100 patients, activated partial thromboplastin time (APTT) was most closely correlated with the prognosis for life, but in 24 patients with DIC, level of serum fibrinogen was most closely correlated with it.

[Fracture of the sella turcica--a case report and review of the literature].

The incidence of a fracture of the sella turcica is reported to be rare and the authors reported a case of a sellar fracture associated with several neurological and endocrinological complications. A 16-year-old boy was struck at the face and the forehead on the road in a motorcycle accident and was hospitalized in a confusional state. Neurological examinations showed dilatation of the both pupils, sluggish light reflex on both sides and bilateral oculomotor palsy but motor weakness or sensory disturbance was not present. On the tenth hospital day, he developed diabetes insipidus and endocrinological examinations disclosed the impairment of GH, LH and FSH reserves, too. Neuroradiological examinations disclosed fractures of bilateral frontal bones and fractures of the left optic canal and ethmoidal roof as well as a fracture of the sella turcica. On the 28th hospital day, he also developed CSF rhinorrhea and pneumocephalus. Surgical repair for the CSF rhinorrhea was performed. Fractures of the sella turcica were reviewed in 23 cases including our personal case and a special consideration regarding the mechanism of sellar fractures and their major complications was made. The authors stressed the early recognition of a fracture of the sella turcica in head injuries, which would suggest a severe hypothalamo-pituitary involvement or other neurological disorders.

Serum cortisol abnormalities after craniocerebral trauma.

Serial estimations of serum cortisol were performed in 49 patients with craniocerebral trauma. Abnormalities of serum cortisol, including alterations in diurnal rhythm and elevations of serum cortisol level, occurred in 21 patients. The frequency and severity of the abnormalities correlated with the severity of the head injury, and there was a trend suggesting that middle fossa basal skull fractures predisposed to cortisol abnormalities. A further 6 patients were studied to assess the effects of exogenous dexamethasone, and in all patients there was suppression of elevated serum cortisol levels by the dexamethasone. The findings suggest that hypercortisolemia after head injury is related to an alteration rather than an abolition of the normal feedback mechanism. (Neurosurgery, 5: 559--565, 1979).