Frailty Could Predict Death in Older Adults after Admissionat Emergency Department? A 6-month Prospective Study from a Middle-Income Country.

BACKGROUND: The number of older adults attending emergency department (ED) is increasing all over the world. Usually, those patients are potentially more complex due to their greater number of comorbidities, cognitive disorders, and functional or physical disabilities. Frailty is a vulnerable state that could predict adverse outcomes of those patients. There are very few studies that addressed this topic in the ED, and none of them used a simple instrument for frailty assessment. OBJECTIVES: The primary outcome was to evaluate the association between frailty identified through the FRAIL questionnaire at baseline and death after a 6-month follow-up period after hospital discharge from the ED. Secondary outcomes were readmission to the ED and disability after 6 months. METHODS: A 6-month follow-up prospective study (FASES study) was conducted at a university-based trauma-center ED in Jundiaí, southwestern of Brazil. A total of 316 older adults aged 60 or older were randomly included based on a lottery of their medical record admission number. Frailty was evaluated through the FRAIL questionnaire. The association between frailty and death was estimated through a binary logistic regression adjusted for age, sex, and cognitive performance. RESULTS: From the total sample, the mean age was 72.11±8.0 years, and 51.6% were women. Participants presented 2.28±1.4 comorbidities and 25.6% were frail. Mean hospital stay was 5.43±5.6 days. Death occurred in 52 participants, readmission to the emergency in 55, and new disability in 16 after 6 months. Frailty was associated with an odds ratio of 2.18 for death after 6 months (95% CI = 1.10-4.31; p = 0.024). This association lost significance after multivariate analysis taking into account cognitive performance. There was no association between frailty status at baseline and readmission to the ED or disability. CONCLUSION: The identification of frailty using the FRAIL at admission was not predictive of death after a 6-month period after discharge from the ED. Simple frailty assessment could identify patients at higher risk for death in the follow-up.

Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.

BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.

Incidence of orolingual angioedema after intravenous thrombolysis for stroke.

INTRODUCTION: Orolingual angioedema (OA) is a known adverse effect of intravenous (i.v.) alteplase. We analyzed all patients treated with i.v. alteplase for stroke at our hospital since approval of i.v. thrombolysis in Italy in 2004 to assess the incidence of this complication. PATIENTS AND RESULTS: Four hundred thirty-three patients received alteplase for stroke from April 2004 to May 2017. Two women developed OA (0.4%; 95% confidence interval 0.1 to 1.6%). Angioedema was mild in one case and severe in the other, with massive swelling of the lips, tongue, and oropharyngeal mucosa, and oropharyngeal bleeding, requiring intubation. Neither patient used ACE-inhibitors. DISCUSSION: The incidence of orolingual angioedema was very low in our series. Although OA is usually mild, anaphylactoid reactions may rarely occur, because of the variable degree of activation of the complement system and kinin cascade caused by alteplase. In such instances, admission to neurointensive care may be required. Specific bradykinin antagonists or drugs that target the kallikrein-kinin system are beginning to be used in the more severe cases. Thus, doctors and nurses caring for acute stroke patients need to be able to recognize and treat this complication.

Heart-fatty acid-binding and tau proteins relate to brain injury severity and long-term outcome in subarachnoid haemorrhage patients.

BACKGROUND: Vasospasm and other secondary neurological insults may follow subarachnoid haemorrhage (SAH). Biomarkers have the potential to stratify patient risk and perhaps serve as an early warning sign of delayed ischaemic injury. METHODS: Serial cerebrospinal fluid (CSF) samples were collected from 38 consecutive patients with aneurysmal SAH admitted to the neurosurgical intensive care unit. We measured heart-fatty acid-binding protein (H-FABP) and tau protein (τ) levels in the CSF to evaluate their association with brain damage, and their potential as predictors of the long-term outcome. H-FABP and τ were analysed in relation to acute clinical status, assessed by the World Federation of Neurological Surgeons (WFNS) scale, radiological findings, clinical vasospasm, and 6-month outcome. RESULTS: H-FABP and τ increased after SAH. H-FABP and τ were higher in patients in poor clinical status on admission (WFNS 4-5) compared with milder patients (WFNS 1-3). Elevated H-FABP and τ levels were also observed in patients with early cerebral ischaemia, defined as a CT scan hypodense lesion visible within the first 3 days after SAH. After the acute phase, H-FABP, and τ showed a delayed increase with the occurrence of clinical vasospasm. Finally, patients with the unfavourable outcome (death, vegetative state, or severe disability) had higher peak levels of both proteins compared with patients with good recovery or moderate disability. CONCLUSIONS: H-FABP and τ show promise as biomarkers of brain injury after SAH. They may help to identify the occurrence of vasospasm and predict the long-term outcome.

Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage.

PURPOSE: The contribution of axonal injury to brain damage after aneurysmal subarachnoid haemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesised that patients with aSAH would have elevated cerebrospinal fluid (CSF) NF-L levels and sought to explore the clinical correlates of CSF NF-L dynamics. METHODS: Serial ventricular CSF (vCSF) samples were collected from 35 patients with aSAH for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analysed in relation to acute clinical status, radiological findings and 6-month outcomes. RESULTS: vCSF NF-L concentrations were elevated in all patients with aSAH. Patients with early cerebral ischaemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial haemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischaemia or 6-month Glasgow Outcome Scale. CONCLUSIONS: Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with ECI. However, our results suggest that axonal injury after aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long-term clinical outcomes.

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF.

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia.

Hypothermia for brain protection in the non-cardiac arrest patient.

This review focuses on the potential application of hypothermia in adults suffering traumatic brain injury (TBI). Hypothermia is neuroprotective, reducing the damaging effects of trauma to the brain in a variety of experimental situations, such as brain ischemia and brain injury, but it has failed to demonstrate outcome improvement in a major controlled, randomized trial. The evidence for the use of hypothermia as a protective procedure is scarce and contradictory. However, evidence does suggest that hypothermia is effective in reducing intracranial hypertension after head injury. Since hypothermia has important side effects, further work is necessary before introducing this procedure into clinical practice for TBI.

Intracranial pressure monitoring for traumatic brain injury: available evidence and clinical implications.

Following traumatic brain injury, uncontrollable intracranial hypertension remains the most frequent cause of death. Despite general agreement on the deleterious effects of elevated intracranial pressure (ICP), however, the evidence supporting the use of ICP monitoring has recently been questioned. The aim of this review was to evaluate the pros and cons of ICP monitoring and to discuss the hypothetical desirability and feasibility of a trial testing the benefits of ICP monitoring.

Increased levels of CSF heart-type fatty acid-binding protein and tau protein after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Heart-type Fatty Acid-Binding Protein (H-FABP) and tau protein (tau) have been shown to be novel biomarkers associated with brain injury and, therefore, they could represent a useful diagnostic tool in patients with subarachnoid hemorrhage (SAH). The goal of this study was to measure H-FABP and tau in cerebrospinal fluid (CSF) following SAH to test the hypothesis that a relationship exists between SAH severity and H-FABP/tau values. METHODS: Twenty-seven consecutive SAH patients admitted to our ICU were studied. Serial CSF samples were obtained in every patient starting on the day of SAH and daily for up to 2 weeks post-SAH. H-FABP/tau levels were measured by enzyme-linked immunosorbent assay. RESULTS: Patients with severe SAH showed significantly higher peak levels of H-FABP and tau compared to mild-SAH patients (FABP: p = 0.02; tay: p = 0.002). In addition the peak concentrations of H-FABP and tau in CSF from SAH patients correlated significantly with Glasgow Coma Scale motor score (H-FABP: Spearman r = -0.52, p = 0.006; tau: Spearman r = -0.63, p = 0.0004). Based on outcome at discharge from the hospital, patients were categorized into survivors and non-survivors. Peak concentrations of both proteins in the non-survivors group were significantly higher than in the survivors. CONCLUSIONS: H-FABP and tau CSF levels are proportional to SAH severity and may be novel biomarkers that can be used to predict the severity of outcome following clinical SAH.

Neuroprotective effect of C1-inhibitor following traumatic brain injury in mice.

BACKGROUND: The goal of the study was to evaluate the effects of Cl-inhibitor (C1-INH), an endogenous glycoprotein endowed with multiple anti-inflammatory actions, on cognitive and histological outcome following controlled cortical impact (CCI) brain injury. METHODS: Male C57B1/6 mice (n=48) were subjected to CCI brain injury. After brain injury, animals randomly received an intravenous infusion of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 microl at 10 min postinjury). Uninjured control mice received identical surgery and saline injection without brain injury. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Mice were subsequently sacrificed, the brains were frozen and serial sections were cut. Traumatic brain lesion was assessed by dividing the area of the ipsilateral hemisphere for the area of the contralateral one at the level of the injured area of the brain. FINDINGS: Brain-injured mice receiving C1-INH at 10 min postinjury showed attenuated cognitive dysfunction compared to brain-injured mice receiving saline (p < 0.01). These mice also showed a significantly reduced traumatic brain lesion compared to mice receiving saline (p < 0.01). Mice receiving C1-INH at 1 hour post injury did not show a significant improvement in either cognitive or histological outcome. Conclusions Our results suggest that administration of C1-INH at 10 minutes postinjury attenuates cognitive deficits and histological damage associated with traumatic brain injury.

Effect of traumatic brain injury on cognitive function in mice lacking p55 and p75 tumor necrosis factor receptors.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has been suggested to play both a deleterious and beneficial role in neurobehavioral dysfunction and recovery following traumatic brain injury (TBI). The goal of this study was to evaluate the specific role of tumor necrosis factor (TNF) receptors p55 and p75 in mediating cognitive outcome following controlled cortical impact (CCI) brain injury by comparing post-traumatic cognitive function in mice with genetically engineered deletion of the gene for either p55 (-/-) or p75 (-/-) receptors. METHOD: Male C57B1/6 mice (WT, n=29), and mice genetically engineered to delete p55 TNF (p55 (-/-), n=8) or p75 TNF (p75 (-/-), n=23) receptors were used. They were anesthetized with intraperitoneal (i.p.) administration of sodium pentobarbital (65 mg/kg) and subjected to CCI brain injury of moderate severity. Sham-injured control mice were anesthetized and surgically prepared similarly but they received no impact. Assessment of mRNA expression of inflammatory, proapoptotic and antiapoptotic genes was done by real time-polymerase chain reaction (RT-PCR). Cognitive outcome was evaluated at 4 weeks postinjury using the Morris water maze (MWM). FINDINGS: mRNA expression of inflammatory, proapoptotic and antiapoptotic genes prior to TBI did not reveal any baseline difference between p55 and p75 (-/-) mice. WT mice showed greater baseline expression of inflammatory genes. The learning ability of p55 (-/-) brain-injured mice was significantly better than that observed in p75 (-/-) brain-injured mice (p < 0.05). Cognitive learning in WT control mice fell between the p55 (-/-) and p75 (-/-) mice. CONCLUSIONS: These data suggest that TNF-alpha may both exacerbate cognitive dysfunction via p55 receptor and attenuate it via p75 receptor.

Experimental models of traumatic brain injury: do we really need to build a better mousetrap?

Approximately 4000 human beings experience a traumatic brain injury each day in the United States ranging in severity from mild to fatal. Improvements in initial management, surgical treatment, and neurointensive care have resulted in a better prognosis for traumatic brain injury patients but, to date, there is no available pharmaceutical treatment with proven efficacy, and prevention is the major protective strategy. Many patients are left with disabling changes in cognition, motor function, and personality. Over the past two decades, a number of experimental laboratories have attempted to develop novel and innovative ways to replicate, in animal models, the different aspects of this heterogenous clinical paradigm to better understand and treat patients after traumatic brain injury. Although several clinically-relevant but different experimental models have been developed to reproduce specific characteristics of human traumatic brain injury, its heterogeneity does not allow one single model to reproduce the entire spectrum of events that may occur. The use of these models has resulted in an increased understanding of the pathophysiology of traumatic brain injury, including changes in molecular and cellular pathways and neurobehavioral outcomes. This review provides an up-to-date and critical analysis of the existing models of traumatic brain injury with a view toward guiding and improving future research endeavors.

Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury.

BACKGROUND: Postischaemic pyrexia exacerbates neuronal damage. Hyperthermia related cerebral changes have still not been well investigated in humans. OBJECTIVE: To study how pyrexia affects neurochemistry and cerebral oxygenation after acute brain injury. METHODS: 18 acutely brain injured patients were studied at the onset and resolution of febrile episodes (brain temperature > or = 38.7 degrees C). Intracranial pressure (ICP), brain tissue oxygen tension (PbrO2), and brain tissue temperature (Tbr) were recorded continuously; jugular venous blood was sampled intermittently. Microdialysis probes were inserted in the cerebral cortex and in subcutaneous tissue. Glucose, lactate, pyruvate, and glutamate were measured hourly. The lactate to pyruvate ratio was calculated. RESULTS: Mean (SD) Tbr rose from 38 (0.5) to 39.3 (0.3) degrees C. Arteriojugular oxygen content difference (AJD(O2)) fell from 4.2 (0.7) to 3.8 (0.5) vol% (p < 0.05) and PbrO2 rose from 32 (21) to 37 (22) mm Hg (p < 0.05). ICP increased slightly and no significant neurochemical alterations occurred. Opposite changes were recorded when brain temperature returned towards baseline. CONCLUSIONS: As long as substrate and oxygen delivery remain adequate, hyperthermia on its own does not seem to induce any further significant neurochemical alterations. Changes in cerebral blood volume may, however, affect intracranial pressure.

[Cerebral oxygen consumption and ischemia in traumatic brain injury]. / Consumo cerebrale di ossigeno e ischemia nel danno cerebrale traumatico.

AIM: Clinical and experimental studies have shown a reduction of cerebral blood flow (CBF) and metabolic alterations following traumatic brain injury (TBI). The incidence of ischemia and the meaning of post-traumatic metabolic alterations are still unclear. METHODS: Revision of CBF and metabolic changes following TBI based on the literature and on our clinical experience. RESULTS: Cerebral ischemia and metabolic alterations are part of the secondary insults/damage leading to an increased damage following TBI. Global ischemia occurs early following TBI as shown by CBF measurements and by greater values of arterio-jugular difference of oxygen (AJDO(2)) during the 1(st) 24 hours postinjury. Post-traumatic ischemia should be defined based on the relationships between CBF and on the metabolic requirements of the brain. Regional ischemia occurs more frequently than global ischemia as shown by regional monitoring of cerebral oxygenation. Following TBI there is a transient phase of increased glycolitic activity followed by a more prolonged phase of reduced metabolic rate of glucose (CMRglc) and oxygen (CMRO(2)). The extent of CMRO(2) reduction is a marker of injury severity and it is associated with unfavorable outcome. CONCLUSION: Cerebral ischemia occurs following TBI and should be defined based on CBF value and the metabolic needs of the brain. Global monitoring of cerebral oxygenation adequacy should be combined with regional monitoring. The meaning of high AJDO(2) values should be reconsidered: if they can highlights potential ischemia they are also showing a still living brain with a partially preserved oxygen extraction capability.

Age-dependent synuclein pathology following traumatic brain injury in mice.

Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in alpha-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.

Head injury, subarachnoid hemorrhage and intracranial pressure monitoring in Italy.

BACKGROUND: Intracranial pressure monitoring is recommended for the management of severe head injury and is increasingly used during intensive care for other pathologies, such as subarachnoid hemorrhage. However, it is still not uniformly applied in different centers. The objectives of this paper are to summarize the frequency and the modalities of intracranial pressure (ICP) monitoring in different centers in Italy; to describe its use in traumatic brain injury (TBI) and in subarachnoid hemorrhage (SAH); and to identify areas for improvement. METHODS: The medical directors of either the neurosurgical department or the intensive care unit, or both, of every Italian neurosurgical center were personally interviewed. They answered specific questions about TBI and SAH patients admitted, and ICP monitoring used, in their units. Data were cleared of any obvious inconsistencies and entered in a database for analysis. All analyses were based simply on the data declared. FINDINGS: The clinical information was obtained from 9137 TBI cases, of whom 4240 severe, and 3151 SAH patients. Among the 106 participating centers, 15 did not use ICP monitoring at all. The remaining 91 had used 3293 ICP devices during the year 2001; 146 were used in tumor cases, 2009 in TBI, and 1138 in SAH. Twenty-two percent of TBI cases admitted to centers with ICP equipment were monitored. Restricting this analysis to severe cases, 47% of TBI with a GCS <8 had ICP. On average, 36% of SAH underwent ICP monitoring. The proportions of head injury and SAH cases who underwent ICP monitoring varied widely in the different centers. Dividing the country into three main areas (north, center and south), there were considerable differences both in the rate of admissions per million inhabitants and in the frequency of ICP monitoring. INTERPRETATION: ICP monitoring in Italy is used in most, but not all, centers. ICP is measured fairly extensively in head injury cases, but a significant proportion of SAH patients is monitored as well. There are substantial differences in the frequency of ICP monitoring in different parts of the country. The use of ICP for both these indications, and the rates of admission to specialized centers, could be improved.