Prognostic Value of Troponins in Patients With or Without Coronary Heart Disease: Is it Dependent on Structure and Biology?

Convincing evidence has emerged that cardiac troponins (cTns) T and I are the biochemical gold standard for diagnosing cardiac injury, and may also be used as efficient screening and risk stratification tools, especially when measured with the new high-sensitivity (hs-) immunoassays. In this narrative review, we aim to explore and critically discuss the results of recent epidemiological studies that have attempted to characterise the prognostic value of cTns in patients with or without cardiovascular disease, and then interpret this information according to cTn biology. Overall, all recent studies agree that higher blood levels of cTns reflect the larger risk of cardiovascular events and/or death, both in the general population and in patients with cardiovascular disease. Additional evidence has shown that the clinical information provided by assessment of both cTns molecules is greater compared to that of either protein alone, and this is mostly due to differential metabolism and clearance of cTnI and cTnT after release in the bloodstream. Although it seems likely that the prognostic value of these biomarkers may be higher than that of other conventional cardiovascular risk factors such as cholesterol or C reactive protein, large and reliable cost-effectiveness investigations are needed to define whether cTns-based population screening may be biologically plausible, clinically effective and economically sustainable.

Association between short- and medium-term air pollution exposure and risk of mortality after intravenous thrombolysis for stroke.

The exposure to air pollutants may increase both incidence and mortality of stroke. We aimed to investigate the association of short- and medium-term exposure to particulate matter (PM) and nitrogen dioxide (NO2) with the outcome of intravenous thrombolysis (IVT) for stroke. We conducted a retrospective analysis based on data prospectively collected from 944 consecutive IVT-treated stroke patients. The main outcome measure was 3-month mortality. The secondary outcome measures were causes of neurological deterioration (≥ 1 NIHSS point from baseline or death < 7 days), including intracerebral hemorrhage, cerebral edema (CED), and persistence or new appearance of hyperdense cerebral artery sign. In the adjusted model, higher PM2.5 and PM10 values in the last 3 days and 4 weeks before stroke were independently associated with higher mortality rate [hazard ratio (HR) 1.014, 95% confidence intervals (CI) 1.005-1.024, p = 0.003; HR 1.079, 95% CI 1.055-1.103, p = 0.001; HR 1.019, 95% CI 1.005-1.032, p = 0.008; and HR 1.015, 95% CI 1.004-1.027, p = 0.007; respectively]. Higher PM2.5 and PM10 values in the last 4 weeks were associated with higher CED rate [odd ratio (OR) 1.023, 95% CI 1.007-1.040, p = 0.006; and OR 1.017, 95% CI 1.003-1.032, p = 0.021; respectively]. No significant association between PM or NO2 and other causes of neurological deterioration was observed. Higher exposure to PM in the last 3 days and 4 weeks before stroke may be independently associated with 3-month mortality after IVT. Higher exposure to PM in the last 4 weeks before stroke may also be independently associated with CED after IVT.

1:1 atrial flutter induced by flecainide, whilst the patient was at rest.

Class Ic antiarrhythmic agents flecainide and propafenone are amongst the drugs most frequently prescribed to control atrial arrhythmias, in particular atrial fibrillation (AF). Despite being cited in some guidelines as a warning when using 1c antiarrhythmic agents, atrial flutter (AFl) with 1:1 atrioventricular conduction is rare in adults, with only small series reported in the literature, mainly including patients having 1:1 AFl during physical activity, and often associated with a predisposing factor, namely a dual AV nodal conduction pathway. We describe here a rare case of 1:1 AFl induced by flecainide, developing whilst the patients was resting in bed, in a 56 year old man who presented to the local Emergency Department (ED) complaining for palpitations due to acute-onset AF. After ED discharge, the patient was then evaluated in the Arrhythmologic Clinic of the Cardiology Department, and channellopaties were excluded. This case report should raise alertness in emergency physicians about this serious and potentially fatal side effect of flecainide, when using this drug for pharmacological cardioversion of AF.

Syncope: current knowledge, uncertainties and strategies for management optimisation in the emergency department.

Admission rates and expenditures for syncope remain high. This unsatisfactory management could be due to several factors, including lack of evidence-based strategy, poor accuracy of clinical decision rules, difficulty in disseminating guidelines, as well as uncertainties concerning management of intermediate-risk patients and role of observation protocols and syncope units. To optimise management, it has been proposed to adopt a pragmatic, symptoms-based definition of syncope and a classification related to the underlying mechanism rather than suspected aetiology. It has also been emphasised the importance of identifying patients at intermediate risk as they can be safely discharged after an intensive emergency department evaluation. A further improvement might result from a research implementation to validate the role of observation protocols and to select patients amenable to be sent to outpatient syncope units. Finally, future studies on prognostic significance of syncope should be performed with a more careful selection of outcomes and a greater uniformity.

Analysis of Temporal and Causal Relationship Between Syncope and 30-Day Events in a Cohort of Emergency Department Patients to Identify the True Rate of Short-term Outcomes.

BACKGROUND: There are a limited number of studies on the short-term prognosis of syncopal patients, and those available are heterogeneous and often have considered events without a clear relationship with the syncopal episode as serious outcomes. OBJECTIVE: The aim of this study was to identify the incidence of short-term true outcomes of a syncopal episode, only considering those occurring after a reasonable period of time, with a plausible causal relationship with index syncope as well as syncopal recurrences causing major trauma. METHODS: In this retrospective, observational study, we assessed all patients managed in the emergency department (ED) during a 6-month period, with 30 days of follow-up. RESULTS: The study population consisted of 982 consecutive syncopal patients. We observed short-term serious events, in a broad sense, in 154 patients (15.7%), the most frequent being dysrhythmias (20.8%), cerebrovascular accidents (18.2%), major traumatic injuries (16.2%), death (13%), and myocardial infarction (9.7%). Most of these events (63.6%) could be identified within 72 h, mainly in the ED. Only 19 patients (2.2% of the sample), experienced a true short-term outcome (7 deaths, 1 myocardial infarction, 9 dysrhythmias, 1 major bleeding event, and 1 traumatic syncopal recurrence). CONCLUSIONS: The incidence of short-term true outcomes of syncope is extremely low. Distinguishing true outcomes from other events has a crucial significance for understanding the real prognostic role of syncope and for planning ED management. Once patients with syncope as a direct consequence of an acute disease needing admission by itself are excluded, most patients with unexplained syncope could be safely discharged after primary evaluation and brief ED monitoring.

Association of Short- and Medium-Term Particulate Matter Exposure with Risk of Mortality after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: We investigated the association of short- and medium-term particulate matter (PM) exposure with risk of mortality in patients with spontaneous intracerebral hemorrhage (ICH) identified according to strict etiologic criteria. METHODS: We conducted a retrospective analysis of prospectively collected data from consecutive patients with spontaneous ICH admitted to the emergency department of the University Hospital of Verona from March 2011 to December 2014. Outcome measures were mortality within 1 month after ICH and significant hematoma expansion (HE) defined as an absolute growth of more than 12.5 mL or a relative increase of more than 50% from baseline to follow-up computed tomography scan. RESULTS: A final number of 308 patients were included. In the adjusted model, higher PM2.5 and PM10 values in the last 3 days (odds ratio [OR] 1.827, 95% confidence interval [CI] 1.057-3.159, P = .031 and OR 1.949, 95% CI 1.025-3.704, P = .042, respectively) and in the last 4 weeks (OR 4.975, 95% CI 2.174-11.381, P < .001 and OR 9.781, 95% CI 3.425-27.932, P < .001, respectively) before ICH were associated with higher mortality rate. No association was found between PM exposure and significant HE. CONCLUSIONS: PM exposure in the short- and medium-term before spontaneous ICH was associated with risk of 1-month mortality, independent of predictors such as age, sex, stroke severity, intraventricular hemorrhage, ICH volume, ICH location, ICH etiologic subtype, significant HE, antithrombotic therapy, atrial fibrillation, and blood glucose levels.

Atypical femoral fractures in Italy: a retrospective analysis in a large urban emergency department during a 7-year period (2007-2013).

The aim of this study was to determine the incidence of atypical femoral fractures (AFFs) seen in a large emergency department in Italy. It was a retrospective study of all men and women aged 40 years or older admitted to the Emergency Department of Parma University Hospital for a femoral fracture. Cases were identified in the hospital database with use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 820 or 821 or text strings. All the radiographic images of fractures not clearly identified as proximal or condylar were retrieved and evaluated by three independent reviewers. Fractures were considered as atypical if all three reviewers agreed on at least four of five major features defined by the 2013 American Society for Bone and Mineral Research criteria. In the 7-year period (2007-2013), with a total follow-up of 1,383,154 patient-years, we found 22 AFFs in 21 patients, accounting for 7.1% of low-trauma subtrochanteric/femoral shaft fractures and 0.6% of all femoral fractures. The incidence was very low (1.6 in 100,000 patient-years in both sexes combined). In contrast, the incidence of classic fractures of the proximal end of the femur was at least two orders of magnitude higher (typical/atypical rate ratio 152). Bisphosphonate use was reported in 13 patients (62%; mean treatment duration 9 years; range 5-14 years). Among 286 patients with typical subtrochanteric/femoral shaft fractures, 20 were being treated with bisphosphonate (7%; odds ratio 22; 95% confidence interval 8-58; p < 0.001). This study confirms the very low incidence of AFFs in the largest Italian cohort of patients to date. Even though the risk is higher in patients treated with bisphosphonates, AFFs are very rare, and typical femoral fractures are at least 100-fold more frequent.

Reporting altered test results in hemolyzed samples: is the cure worse than the disease?

The management of laboratory data in unsuitable (hemolyzed) samples remains an almost unresolved dilemma. Whether or not laboratory test results obtained by measuring unsuitable specimens should be made available to the clinicians has been the matter of fierce debates over the past decades. Recently, an intriguing alternative to suppressing test results and recollecting the specimen has been put forward, entailing the definition and implementation of specific algorithms that would finally allow reporting a preanalytically altered laboratory value within a specific comment about its uncertainty of measurement. This approach carries some advantages, namely the timely communication of potentially life-threatening laboratory values, but also some drawbacks. These especially include the challenging definition of validated performance specifications for hemolyzed samples, the need to producing reliable data with the lowest possible uncertainty, the short turnaround time for repeating most laboratory tests, the risk that the comments may be overlooked in short-stay and frequently overcrowded units (e.g. the emergency department), as well as the many clinical advantages of a direct communication with the physician in charge of the patient. Despite the debate remains open, we continue supporting the suggestion that suppressing data in unsuitable (hemolyzed) samples and promptly notifying the clinicians about the need to recollect the samples remains the most (clinically and analytically) safe practice.

Cardiac troponins and mortality in type 1 and 2 myocardial infarction.

BACKGROUND: The pathogenesis of different types of myocardial infarction (MI) differs widely, so that accurate and timely differential diagnosis is essential for tailoring treatments according to the underlying causal mechanisms. As the measurement of cardiac troponins is a mainstay for diagnosis and management of MI, we performed a systematic literature analysis of published works which concomitantly measured cardiac troponins in type 1 and 2 MI. METHODS: The electronic search was conducted in Medline, Scopus and Web of Science using the keywords "myocardial infarction" AND "type(-)2" OR "type II" AND "troponin" in "Title/Abstract/Keywords", with no language restriction and date limited from 2007 to the present. RESULTS: Overall, 103 documents were identified, but 95 were excluded as precise comparison of troponin values in patients with type 1 and 2 MI was unavailable. Therefore, eight studies were finally selected for our analysis. Two studies used high-sensitivity (HS) immunoassays for measuring cardiac troponin T (HS-TnT), one used a HS immunoassay for measuring cardiac troponin I (HS-TnI), whereas the remaining used conventional methods for measuring TnI. In all studies, regardless of type and assay sensitivity, troponin values were higher in type 1 than in type 2 MI. The weighted percentage difference between type 1 and 2 MI was 32% for TnT and 91% for TnI, respectively. Post-discharge mortality obtained from pooling individual data was instead three times higher in type 2 than in type 1 MI. CONCLUSIONS: The results of our analysis suggest that the value of cardiac troponins is consistently higher in type 1 than in type 2 MI.

Early function decline after ischemic stroke can be predicted by a nomogram based on age, use of thrombolysis, RDW and NIHSS score at admission.

The availability of prediction tools for risk stratification after acute stroke is seen as a valuable perspective for tailored clinical management. This retrospective study was aimed to identify significant predictors of poor outcome in patients presenting with acute ischemic stroke, which could then be used for constructing a prediction model. The study population consisted of 837 patients admitted to the Stoke Unit of University Hospital of Verona (Italy) for acute ischemic stroke within 12 h of symptoms onset. In multivariate analysis, age, use of thrombolysis, red blood cell distribution width (RDW) and NIHSS score at admission were found to be significant predictors of 3-month functional decline. A nomogram constructed by integrating these four variables exhibited an area under the curve of 0.832 for predicting functional impairment. The >80% risk cut-off derived from the nomogram was associated with 0.91 positive predictive value, whereas a risk probability <10% displayed 0.93 negative predictive value for predicting functional impairment. These results demonstrate that a prediction tool integrating some important clinical, laboratory and demographic variables may enable an efficient risk stratification of poor outcome after acute stroke.

Massive pneumomediastinum following orbital fracture.

Pneumomediastinum is a rare complication of facial fractures, always persuading the physicians to search for other and potentially more serious injuries such as esophageal or tracheal rupture. A 75-year old man presented to the Emergency Department (ED) reporting an accidental fall while walking on the road. He did not report loss of consciousness (LOS), was not taking anticoagulant drugs, did not report chest, abdomen or limb trauma. On physical examination he only showed swelling of nose and right orbit. The patient underwent a Computed Tomography (CT) scan of head and facial bones, showing a complex fracture involving right nasal bone, ethmoid, right orbital lateral wall, and right maxillary sinus lateral wall. No intracranial lesions were found. Due to the finding of subcutaneous emphysema in the right cheek, the scan was extended to the whole neck and chest. The exam showed a massive pneumomediastinum, extending till the diaphragmatic hiatus. The patient thus underwent bronchoscopy and esophagogastroscopy, but no further lesions could be found. Antibiotics therapy was then administered, and was discharged in good conditions after a five-days observation. In our patient, air had probably escaped into the pharyngo-maxillary space from the right maxillary sinus and tracked into both the retropharyngeal space and, for contiguity, into the pre-tracheal space. As our case report shows, if the airway is secure, the pneumomediastinum does not necessarily require treatment other than clinical observation and management of the fracture. If no other injuries are present, resolution of the pneumomediastinum may be expected without further medical interventions.

Incidence of primary spontaneous pneumothorax is not associated with microclimatic variations. Results of a seven-year survey in a temperate climate area.

Some diseases, such as renal colic and atrial fibrillation, display an association with microclimatic variations. In particular, despite a correlation has been reported between incidence of primary spontaneous pneumothorax (PSP) and meteorological variations, the evidence remains poor and conflictual. The aim of this study was to assess the influence of day-by-day meteorological variations on the number of visits for PSP in the Emergency Department (ED). All PSP cases were retrieved from the hospital database from January 2008 to December 2014. For all the observational days, meteorological data about the Parma Province were obtained from the Environment and Climate Regional Agency.  The correlation between ED visits for PSP and variation of air temperature (T°), atmospheric pressure (hPa) and humidity (%) was then tested. The chronological data of all the visits for PSP were correlated with climate data by univariate linear regressions analysis. A total number of 608.215 ED visits were recorded during the observational period, with an average of 238 patients per day. Overall, 257 PSP cases were observed (mean age 37±21 years), 79% males and 21% females. No significant correlation between average daily visits for SP and daily change of average temperature, humidity, or atmospheric pressure was observed throughout the observational period (p>0.05 for all). The results of the study show that the incidence of PSP is not significantly associated with changes of microclimatic variables.

The Mean Platelet Volume Is Decreased in Patients Diagnosed with Venous Thromboembolism in the Emergency Department.

Platelets are small corpuscular elements, which play an essential role in hemostasis and thrombosis. As active players in the thrombotic process, hyperactive platelets are involved in the pathogenesis of cardiovascular disorders. Nevertheless, the role of platelet size, as a biological marker of platelet activation, remains debated in the setting of venous thrombosis. Therefore, we conducted a retrospective case-control study to clarify the potential association between mean platelet volume (MPV) and newly diagnosed venous thromboembolism (VTE) by reviewing data of all consecutive patients receiving a diagnosis of VTE at the emergency department (ED) of the University Hospital of Parma (Italy) between January and December, 2014. The control population was represented by outpatients undergoing routine laboratory testing for health checkup at the phlebotomy center of the same University Hospital during the same period. MPV was found to be comparatively decreased in the entire cohort of patients with VTE compared with the outpatient population, as well as in those with isolated deep vein thrombosis (DVT) or pulmonary embolism (PE). A decreased MPV value (i.e., < 10.8 fL) was found to be associated with an increased risk of diagnosing VTE (relative risk, 1.18; 95% CI, 1.09-1.28; p < 0.001), as well as of diagnosing isolated DVT (relative risk, 1.19; 95% CI, 1.07-1.31; p = 0.001) and isolated PE (relative risk, 1.17; 95% CI, 1.04-1.30; p = 0.007). A decreased MPV value in active cancer patients was associated with the highest risk of diagnosing thrombosis (relative risk, 1.29; 95% CI, 1.10-1.51; p = 0.002). These results support an inverse association between MPV and the risk of venous thrombosis at diagnosis.

A Web Site to Improve Management of Patients with Inherited Bleeding Disorders in the Emergency Department: Results at 2 Years.

Treatment of patients with inherited bleeding disorders (PWIBD) in the emergency department (ED) is challenging. In 2010, a project was started involving all eight hemophilia centers (HC) and all 44 EDs of the Region of Emilia-Romagna (Italy) to improve emergency care for PWIBD. The project incorporates guidelines for emergency treatment, education for ED staff, and a dedicated Web site providing extensive information, proposing treatments, and sharing data with patients' electronic clinical records. A Web algorithm, accessible to PWIBD as well as ED and HC staff, suggests the first dose of concentrate for each type and severity of bleed or trauma. Following training courses in each ED, the network was activated. During 2012 and 2013, the site was visited 14,000 times, the EDs accessed the Web site 1,739 times, and used the algorithms 206 times. In two reference EDs, triage-assessment and triage-treatment times were reduced in 2013 and 2012 (27/20 and 110/71.5 minutes, respectively) and medical advice from the HC increased (54 vs. 24% cases). The main advantages of this system are better management of patients in ED (shorter triage-to-treatment times) and improved collaboration between HCs and EDs. The most critical point remaining is staff turnover in EDs, necessitating continual training.

Hypoglycemia Alert Dogs: A Novel, Cost-effective Approach for Diabetes Monitoring?

The recent publication of the results of 3 small trials, and as many as 5 case reports on dogs producing clear and intelligible alerts in the presence of their owners' hypoglycemia, opens an intriguing clinical scenario for management of diabetes. The skill seems attributable to the ability of dogs to identify patterns in skin and breath odors as well as to understand and interpret visual cues from humans during hypoglycemia. Provided that further trials can confirm the findings, the use of diabetes alert dogs that are trained to detect the onset of hypoglycemia can be regarded as a fast, versatile, reliable, and cost-effective approach for safeguarding the health of individuals with diabetes.

Red blood cell distribution width and haemoglobin are associated with hospital admission in patients with acute allergic reactions.

INTRODUCTION: Red blood cell distribution width (RDW) is significantly associated with a variety of human disorders. This study aimed to investigate whether RDW value at admission may predict the need of hospitalisation in patients presenting to the emergency department (ED) with acute allergic reactions. MATERIALS AND METHODS: The study population consisted of adult patients (aged > 17) admitted to the ED for acute allergic reactions. RESULTS: One hundred and thirty-two subjects were included, 12 of whom (9%) required hospital admission for severity of symptoms. Patients who needed hospital admission displayed significantly lower values of haemoglobin and significantly higher values of RDW-coefficient of variation (RDW-CV). In multivariate analysis, haemoglobin and RDW-CV were found to be independent predictors of hospital admission. The area under the curve (AUC), sensitivity and specificity for predicting hospital admission were 0.72, 0.88 and 0.42 for haemoglobin and 0.73, 0.88 and 0.50 for RDW-CV, respectively. The combination of these tests (both positive) was characterised by 0.76 AUC, 0.83 sensitivity, 0.67 specificity, 0.96 negative predictive value and 0.30 positive predictive. DISCUSSION: The results of this study suggest that two common and inexpensive parameters such as haemoglobin and RDW are independent predictors of hospital admission in patients presenting to the ED with acute allergic reactions.

Quality and safety issues of direct oral anticoagulants in the emergency department.

The direct oral anticoagulants (DOACs) are increasingly used in patients with atrial fibrillation and venous thromboembolism. The decision making of clinicians and especially emergency physicians for the appropriate management of patients taking DOACs entails a thorough understanding of pharmacologic profile, practical guidance on their usage, and management of bleeding and/or thrombotic events. The available evidence suggests that the bleeding complications observed in patients taking DOACs are less frequent and potentially less severe than those in patients taking vitamin K antagonists or heparins. This should be regarded as an advantage for emergency physicians, since it would decrease the admission rate of anticoagulated patients and probably require a less aggressive treatment in the emergency department (ED). The greatest challenge of DOACs is so far represented by the lack of clinically usable antidotes, since these (i.e., idarucizumab, andexanet alfa, and aripazine) are in different phases of development. A second major concern is the current lack of consensus about laboratory monitoring for these drugs. Although there is widespread perception that patients on DOACs do not require dose adjustment based on laboratory testing, in some selected clinical situations, laboratory testing may be taken into consideration in the ED. The type of laboratory diagnostics needed for emergency management should hence include tests that are promptly available, affordable to all stat laboratories, and cost effective. The aim of this article is to provide a personal overview on quality and safety issues of DOACs with an ED perspective.

Cell-free DNA for diagnosing myocardial infarction: not ready for prime time.

A modest amount of cell-free DNA is constantly present in human blood, originating from programmed cell death, apoptosis and rupture of blood cells or pathogens. Acute or chronic cell injury contributes to enhance the pool of circulating nucleic acids, so that their assessment may be regarded as an appealing perspective for diagnosing myocardial ischemia. We performed a search in Medline, Web of Science and Scopus to identify clinical studies that investigated the concentration of cell-free DNA in patients with myocardial ischemia. Overall, eight case-control studies could be detected and reviewed. Although the concentration of cell-free DNA was found to be higher in the diseased than in the healthy population, the scenario was inconclusive due to the fact that the overall number of subjects studied was modest, the populations were unclearly defined, cases and controls were not adequately matched, the methodology for measuring the reference cardiac biomarkers was inadequately described, and the diagnostic performance of cell-free DNA was not benchmarked against highly sensitive troponin immunoassays. Several biological and technical hurdles were also identified in cell-free DNA testing, including the lack of specificity and unsuitable kinetics for early diagnosis of myocardial ischemia, the long turnaround time and low throughput, the need for specialized instrumentation and dedicated personnel, the lack of standardization or harmonization of analytical techniques, the incremental costs and the high vulnerability to preanalytical variables. Hence it seems reasonable to conclude that the analysis of cell-free DNA is not ready for prime time in diagnostics of myocardial ischemia.

Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury.

BACKGROUND: Brain injury is a medical emergency that needs to be diagnosed and treated promptly. Several proteins have been studied as biomarkers of this medical condition. The aims of this study were to: 1) evaluate the selectivity and precision of a commercial ELISA kit for neurofilament medium polypeptide (NFM) protein; and 2) evaluate the concentration in cerebrospinal fluid (CSF) and serum of healthy individuals and patients with brain damage. METHODS: An ELISA from Elabscience was used. The selectivity was evaluated using size-exclusion chromatography and mass spectrometry. Intra- and inter-batch coefficients of variation (CV) were also studied. Fifty-one CSF samples from 36 age-matched patients with hemorrhagic stroke (HS) (n=30), ischemic stroke (IS) (n=11) and healthy individuals (n=10) were assayed. In addition, serum samples from healthy volunteers (n=47), 68 serum samples from seven patients with HS, 106 serum samples from 12 patients with traumatic brain injury (TBI) and 68 serum samples from 68 patients with mild traumatic brain injury (mTBI) were also analyzed. RESULTS: NFM was identified in the chromatographic fraction with highest immunoreactivity. The intra- and inter-batch CVs were ≤10% and ≤13%, respectively. The CSF-NFM concentration in HS was significantly higher (p<0.0001) than in IS and controls. Serum NFM concentration ranged from 0.26 to 8.57 ng/mL in healthy individuals (median=2.29), from 0.97 to 42.4 ng/mL in HS (median=10.8) and from 3.48 to 45.4 ng/mL in TBI (median=14.7). Finally, 44% of patients with mTBI had increased NFM concentration, with significantly higher levels (p=0.01) in patients with polytrauma. CONCLUSIONS: To our knowledge this is the first study describing increased NFM levels in CSF and serum from patients with brain damage.

Epidemiological association between migraine and lipoprotein(a): a systematic review.

Migraine is a relatively frequent and disabling condition, which poses a large clinical and economical burden on human society. Since there is now emerging evidence that the risk of cardiovascular diseases may be significantly increased in patients with migraine, and that lipoprotein(a) is a powerful, independent cardiovascular risk factor, we performed an electronic searched on Medline, Scopus and Web of Science using the keywords "migraine" and "lipoprotein(a)" or "apolipoprotein(a)" or "Lp(a)" or "apo(a)", with no language or date restriction. The electronic search produced four cross-sectional studies which reported original data about the epidemiological association between lipoprotein(a) and migraine, and used standardized criteria for diagnosing migraine. In only one out of the four studies the concentration of lipoprotein(a) was found to be higher in migraineurs than in controls, whereas in the remaining three investigations lipoprotein(a) levels were found to be virtually identical between cases and controls. This analysis suggests that if any epidemiological and clinical link exists between migraine and cardiovascular disease, a direct involvement of lipoprotein(a) seems unlikely according to the available epidemiological evidence.