Plaque neovascularization detected with contrast-enhanced ultrasound predicts ischaemic stroke recurrence in patients with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast-enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels in vivo. Our aim was to determine if CEUS-detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow-up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence. RESULTS: We included 78 patients whose mean age was 74.3 ± 10.4 years. There were 29 (37.2%) patients with a low-grade stenosis (<50%). The remainder presented moderate (50%-69%) or high-grade (≥70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow-up of 14.1 (interquartile range, 9.5-19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS-detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66-26.01). CONCLUSION: In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.

Insular damage, new-onset atrial fibrillation and outcome after acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Cortical insular damage is associated with cardiac arrhythmias and an increased risk of death. We investigated the influence of insular damage on the outcome of patients with acute intracerebral hemorrhage as well as the frequency and predictors of new-onset atrial fibrillation (nAF). METHODS: We studied consecutive patients with intracerebral hemorrhage from 2013 to 2016. We identified those patients who underwent continuous electrocardiographic monitoring (≥24 h), known atrial fibrillation and recent ischemic stroke. We prospectively collected demographic data, vascular risk factors, neurological severity, vital signs, radiological data, nAF and mortality at 3 months. Bivariate and multivariate regression analyses were performed. RESULTS: We evaluated 347 patients whose mean age was 73.5 ± 14.0 years (50.7% of them were men). We selected 183 patients to study the frequency and risk factors of nAF (mean age, 69.1 ± 14.7 years; 52.5% of them were men). We observed that 11/183 (6.0%) had nAF. Insular damage [odds ratio (OR), 7.6; 95% confidence interval (CI), 2.1-27.7] was associated with nAF. A total of 138/347 patients died within the first 3 months and insular damage was detected in 99/347 of them. Predictors of death were age (OR, 1.07; 95% CI, 1.04-1.10), blood glucose (OR, 1.00 per mg/dL;, 95% CI, 1.00-1.01), Glasgow Coma Scale score (OR, 0.85; 95% CI, 0.77-0.92), hematoma volume (OR, 1.02 per mL; 95% CI, 1.01-1.04), intraventricular hemorrhage (OR, 1.93; 95% CI, 1.03-3.64) and insular damage (OR, 3.98; 95% CI, 2.00-7.90). CONCLUSIONS: The frequency of nAF in our patients was 6.0%. Insular damage was a risk factor for nAF and an independent predictor of death at 3 months.

Does prior antiplatelet therapy influence hematoma volume and hematoma growth following intracerebral hemorrhage? Results from a prospective study and a meta-analysis.

BACKGROUND AND PURPOSE: Large baseline hematoma volume (HV) and hematoma growth (HG) are related to poor outcome in patients with intracerebral hemorrhage (ICH). It remains controversial whether prior antiplatelet therapy (APT) influences baseline HV and HG, and the outcome following ICH. METHODS: We collected clinical and radiological data from a prospective cohort of patients diagnosed with ICH within 24 h of symptom onset. Prior APT was ascertained from the clinical history. In patients for whom a follow-up computed tomography (CT) was available within 72 h, we assessed HG, defined as an increase of ≥33% and/or ≥12.5 mL in the HV. We assessed mortality and functional outcome during follow-up with the Rankin scale. To perform a meta-analysis, we searched for published studies reporting HG according to previous APT and pooled the available data. RESULTS: We included 223 patients (mean age 72.5 ± 13 years). Previous APT was reported in 74 patients (33.2%). The linear regression model showed that prior APT was independently associated with larger baseline HV. HG was detected in 49 of 130 patients (37.7%) and no differences related to prior APT were observed among our cohort. However, after pooling the data of seven studies in the meta-analysis, prior APT showed an increase in HG frequency (odds ratio, 1.85; 95% confidence interval, 1.37-2.5). Patients who received APT presented with worse outcome during follow-up, although this difference was not significant (P = 0.06). CONCLUSIONS: In the current study, prior APT was related to larger baseline HV in patients with ICH. Data from the meta-analysis also showed a higher risk of HG associated with APT.

Visual hallucinations in patients with acute stroke: a prospective exploratory study.

BACKGROUND AND PURPOSE: The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated. METHODS: Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge. RESULTS: In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively). CONCLUSIONS: Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.

Left atrial appendage closure in patients with intracranial haemorrhage and atrial fibrillation. / Cierre de orejuela en pacientes con hemorragia intracraneal y fibrilación auricular.

INTRODUCTION: The use of oral anticoagulants in patients with a history of atrial fibrillation (AF) and intracranial haemorrhage (ICH) is controversial on account of the risk of haemorrhagic stroke recurrence. This study presents our experience regarding the safety and efficacy of percutaneous left atrial appendage closure (LAAC), an alternative to anticoagulation in these patients. METHODS: We conducted a retrospective, single-centre, observational study. LAAC was performed in patients with a history of ICH and non-valvular AF. Risk of ischaemic and haemorrhagic events was estimated using the CHA2DS2-VASc and HAS-BLED scales. We recorded periprocedural complications, IHC recurrence, cerebral/systemic embolism, mortality and use of antithrombotic drugs following the procedure. RESULTS: LAAC was performed in 9 patients (7 men, 2 women) using the AMPLATZER Amulet device in 7 cases and the AMPLATZER Cardiac Plug device in 2. Mean age was 72.7±8.2 years. Time between ICH and LAAC was less than one month in 5 patients and more than one month in 4 patients. Median CHA2DS2-VASc score was 4 (interquartile range of 2.5). Median HAS-BLED score was 3 (interquartile range of 0). No periprocedural complications were recorded. All patients received single anti-platelet therapy (clopidogrel in 5 patients, aspirin in 4) after the procedure; 5 patients received this treatment for 6 months and 4 received it indefinitely. No ischaemic or haemorrhagic events were recorded during follow-up (mean duration of 15 months). CONCLUSIONS: In our series, LAAC was found to be safe and effective in patients with a history of ICH who required anticoagulation due to AF.

Reliability of point-of-care coagulometer measurements in patients with acute ischaemic stroke receiving intravenous fibrinolysis. / Fiabilidad del coagulómetro portátil en pacientes con ictus isquémico agudo tratados con fibrinólisis intravenosa.

BACKGROUND: Speed of administration conditions the effectiveness of intravenous fibrinolysis in treating acute ischaemic stroke. To reduce the risk of haemorrhagic complications, the intervention is contraindicated in certain cases, such as where the International Normalised Ratio (INR) is ≥ 1.7. This study aimed to determine the reliability of point-of-care INR readings (POC-INR) taken using the CoaguChek® XS portable coagulometer compared to laboratory results (L-INR). METHODS: We conducted a retrospective observational study of consecutive patients admitted to our centre with acute ischaemic stroke and who were treated with intravenous fibrinolysis, over a period of 4 years. Patients' INR was measured with a portable coagulometer and in the laboratory. Results were compared using the paired-sample t test; using L-INR results as a reference value, ROC analysis was performed to determine POC-INR with greater predictive value. RESULTS: The study included 210 patients with a mean age of 74.3±11.5 years old; 18 (8.6%) were taking vitamin K antagonist oral anticoagulants (OAC). There were no significant differences between the 2 INR measurements in the population as a whole (POC-INR-L-INR difference: 0.001±0.085; P=.82). In subgroup analysis, the results coincided for patients taking OACs (0.001±0.081; P=.42) and those with L-INR ≤ 1.2 (0.008±0.081; P=.16). For L-INR>1.2, however, the portable coagulometer underestimated INR (0.058±0.095; P=.01). Through ROC analysis, POC-INR < 1.6 was found to be the cut-off point with greatest sensitivity (100%) and specificity (98.97%) for identifying patients eligible for intravenous fibrinolysis (L-INR < 1.7). CONCLUSIONS: POC-INR shows a good correlation with L-INR. Our results suggest that the best threshold to predict an L-INR < 1.7 is POC-INR < 1.6. Internal validation studies for POC-INR should be considered in all treatment centres.

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma-induced coagulopathy: a randomized open-label trial.

Essentials An immediate supply of plasma in case of trauma-induced coagulopathy is required. The Traucc trial compared French Lyophilised Plasma (FLyP) and Fresh Frozen Plasma (FFP). FLyP achieved higher fibrinogen concentrations compared with FFP. FLyP led to a more rapid coagulopathy improvement than FFP. SUMMARY: Background Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy. Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6 h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45 min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality. Results Forty-eight patients were randomized (FLyP, n = 24; FFP, n = 24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90] min). FLyP achieved a higher fibrinogen concentration 45 min after randomization compared with FFP (baseline-adjusted mean difference, 0.29 g L-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6 h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP. Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.

[Is the research of posttransfusional alloantibodies still relevant?] / Est-ce que la réalisation de la recherche d'anticorps antiérythrocytaires post­transfusionnelle est toujours pertinente ?

The decision of November 6th, 2006 defining the principles of best practices recommends that posttransfusional red cell alloantibodies research is performed after one to three months after. In the University hospital of Brest, the haemovigilance unit takes charge of sending the medical prescription within the required time and centralizing the results. We wished to estimate if the realization of this research still remains relevant. METHODS: A prospective analysis was performed in 2015. We evaluated the realization rate, the red cell alloantibodies rate and the recipient adverse reactions with the diagnostic category: alloimmunization (delayed serological transfusion reaction, DSTR). RESULTS: In 2015, 2162 prescriptions were sent to the 3271 transfused patients. One thousand and eighteen red cell alloantibodies research were done, i.e. a return rate of 61%. Among them, 12 alloantibodies appeared (0.9%) within an average of 56 days. Thirty-three other alloantibodies appeared and were discovered most frequently before a new transfusion. In 10 cases, a posttransfusional research was done that was negative. A survey was conducted among GHCOH members to describe the practices in these health institutions. Twelve questionnaires were analysed. Ten institutions performed a posttransfusional alloantibodies research by issuing a prescription at the patient's exit with a return rate between 0.14 and 16%; 1 institution has a centralized organization with a return rate of 68.3%; 1566 red cell alloantibodies research were performed and among them, 24 alloantibodies appeared (1.53%). CONCLUSION: These results indicate that to be effective, the management of this biological test must be centralized. Despite this, the red cell alloantibodies rate remains very low (0.9 and 1.53%) and raises the question of the relevance of this systematic testing after transfusion, which is in any case mandatory before a new transfusion of red blood cells.

[Assessment of knowledge in blood transfusion of medical staff in 14 state-run hospitals]. / Evaluation des connaissances médicales transfusionnelles dans 14 établissements publics de santé

UNLABELLED: This multi-centre study aimed to assess the knowledge in blood transfusion of medical staff in 14 state-run hospitals. MATERIALS AND METHODS: A questionnaire was distributed to all potential prescribers of blood products. It contained 35 questions concerning various subjects: blood products, immuno-haematology, prescription of blood products, transfusion practice, interpretation of the final bedside controls. The rate of correct answers (RCA) was obtained for each question, for each subject, and for nine questions defined as essential for patient safety. A weighted score was also calculated by ranking each question between one and six according to its importance. RESULTS: Six hundred and ninety four questionnaires were analysed (rate of return 15%). The RCA ranged from 14 to 89%, according to the questions. The RCA ranged from 47 to 78% for seven of the nine essential safety questions, and 82% and 83% for the two questions concerning the interpretation of incompatible final bedside controls: there were 9% of wrong answers, which validated an incompatible blood transfusion. The mean weighted score was 62%. Both the RCA and the weighted score were higher for those that regularly prescribe blood products than for that only prescribe them occasionally. There were no significant differences between hospitals. CONCLUSION: This study has confirmed that medical staff have deficiencies in their knowledge of blood transfusion, deficiencies which are acknowledged by medical staff. These first results will help the members of the study group to develop and prioritize various actions to improve this state of affairs, and to follow the effects of the training given.

Transcranial Duplex Sonography Predicts Outcome following an Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Several radiologic features such as hematoma volume are related to poor outcome following an intracerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage. MATERIALS AND METHODS: We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs. We correlated these data with the CT scans and assessed the prognostic value of the transcranial duplex sonography measurements. We assessed early neurologic deterioration during hospitalization and mortality at 1-month follow-up. RESULTS: We included 35 patients with a mean age of 72.2 ± 12.8 years. Median baseline hematoma volume was 9.85 mL (interquartile range, 2.74-68.29 mL). We found good agreement and excellent correlation between transcranial duplex sonography and CT when measuring hematoma volume (r = 0.791; P < .001) and midline shift (r = 0.827; P < .001). The logistic regression analysis with transcranial duplex sonography measurements showed that hematoma volume was an independent predictor of early neurologic deterioration (OR, 1.078; 95% CI, 1.023-1.135) and mortality (OR, 1.089; 95% CI, 1.020-1.160). A second regression analysis with CT variables also demonstrated that hematoma volume was associated with early neurologic deterioration and mortality. When we compared the rating operation curves of both models, their predictive power was similar. CONCLUSIONS: Transcranial duplex sonography showed an excellent correlation with CT in assessing hematoma volume and midline shift in patients with intracerebral hemorrhage. Hematoma volume measured with transcranial duplex sonography was an independent predictor of poor outcome.

[Platelet transfusion and allergic transfusion reactions: experiences at Lille Hospital over a four year period]. / Transfusion de plaquettes et incidents de type allergique: expérience du CHRU de Lille sur une période de quatre ans.

Among the immediate transfusion reactions caused by the utilization of blood products, those suggesting immuno-allergic mechanisms posed problems for frequency, gravity, laboratory diagnosis and safety. We report here the Lille Hospital's experience over a four-year period concerning these manifestations after platelet concentrate transfusion. Eight hundred and fifty-two immediate transfusion reactions have been declared, of which 230 were allergic, which appeared in 181 patients (27%). Among the most frequent clinical signs, rash was often described (158 cases: 68.7%); less frequent were respiratory problems such as dyspnea (34 cases: 14.8%) and hypotensive reactions (18 cases: 7.8%). Seven patients presented severe reactions (3%). Twenty percent of them presented multiple allergic reactions and in 43.2%, the recurrence was more serious than the initial problem in spite of preventive medication; the use of washed blood components was necessary. The age of platelet concentrates does not appear to play a part in provoking these events (67% of platelet concentrates had been collected within four days). These allergic transfusion reactions posed problems for those who prescribe medication, because they are frequent, sometimes serious, can recur and at present, the proposed medication prevention is not always efficient.

[Diagnostic difficulties of transfusion incidents due to bacterial contamination: report of two cases]. / Difficultés diagnostiques des incidents transfusionnels par contamination bactérienne: à propos de deux observations.

The French hemovigilance system has recently underlined the relative frequency of transfusion-associated bacterial sepsis and the necessity to remain constantly aware of this eventuality. We describe the experience of a hematology unit over a 18-month period: 189 acute transfusion reactions were registered and bacterial cultures of the implicated cellular blood products realized in 82 of them. A positive result was obtained in two cases. For both cases, clinical symptoms of transfusion reaction were limited to a lasting fever, and a skin rash occurred in aplastic patients with preexisting signs of sepsis. The causal relationship between this contamination and the transfusion reaction is difficult to establish. Clinical manifestations justifying a bacterial inquiry must therefore be more precisely defined, particularly in multitransfused patients.

[Impact of a quality approach for transfusion safety on prescription, circuit optimization, traceability]. / Impact d'une démarche qualité en sécurité transfusionnelle sur la prescription, l'optimisation des circuits, la traçabilité. Expérience du CHRU de Lille.

The Quality Assessment Program undertaken at the Regional University Hospital of Lille benefits from previous experience making management of this project possible: continuing education, preliminary initiation into the quality approach, and existing reference systems. The aims are to master the rates of outdated and no longer efficient red cell concentrates, to control red cell concentrate delivery time, to validate the refrigeration line integrity and to ensure a flawless marking out process. The process studied is transverse, with those taking part in it belonging to several professional categories. The method will consist in a process identification, its description and characterization according to FMECA (Failure Mode Effects and Criticality Analysis), the creation of a new process and its improvement. Thus failures should be identified and classified hierachically. The corrective actions will consist in communication aids, an education program, blood product transport and blood depot reorganization, data processing improvement and medical equipment acquisition. Quality indicators are developed according to the objectives of the study, and progress indicators are developed as a periodical assessment of blood transfusion practice. This ambitious project relies on the involvement of Hospital Management and referent network. These referents facilitate the improvement processes for those taking part in this process.

The Posidonia oceanica marine sedimentary record: A Holocene archive of heavy metal pollution.

The study of a Posidonia oceanica mat (a peat-like marine sediment) core has provided a record of changes in heavy metal abundances (Fe, Mn, Ni, Cr, Cu, Pb, Cd, Zn, As and Al) since the Mid-Holocene (last 4470yr) in Portlligat Bay (NW Mediterranean). Metal contents were determined in P. oceanica. Both, the concentration records and the results of principal components analysis showed that metal pollution in the studied bay started ca. 2800yr BP and steadily increased until present. The increase in Fe, Cu, Pb, Cd, Zn and As concentrations since ca. 2800yr BP and in particular during Greek (ca. 2680-2465cal BP) and Roman (ca. 2150-1740cal BP) times shows an early anthropogenic pollution rise in the bay, which might be associated with large- and short-scale cultural and technological development. In the last ca. 1000yr the concentrations of heavy metals, mainly derived from anthropogenic activities, have significantly increased (e.g. from ~15 to 47µg g(-1) for Pb, ~23 to 95µg g(-1) for Zn and ~8 to 228µg g(-1) for As). Our study demonstrates for the first time the uniqueness of P. oceanica meadows as long-term archives of abundances, patterns, and trends of heavy metals during the Late Holocene in Mediterranean coastal ecosystems.

[Suitability of red blood cell transfusion: a multicenter study]. / Évaluation multicentrique de la pertinence des prescriptions de concentrés de globules rouges.

The purpose of this retrospective observational multicenter study was to assess appropriateness of red blood cell (RBC) transfusion, according to the French national guidelines (Agence française de sécurité sanitaire des produits de santé) published in 2002. Six hundred and thirty-nine RBC transfusions from nine institutions have been randomly selected and analysed. The data collected are issued from different specialities. Patients' characteristics, occurrences of transfusion, admission, pre-transfusion, post-transfusion and discharge haemoglobin concentrations have been collected. Two physicians (who are in charge) must evaluate the appropriateness of pre-transfusion, discharged haemoglobin concentrations, quantity and quality of transfused RBC. The mean pre-transfusion haemoglobin concentration was 7.89 ± 1.24, the median number of transfused RBC was two (extremes: 1-16), the mean discharge haemoglobin concentration was 10.14 ± 1.30 (-5 days after the end of transfusion). The pre-transfusion and discharge haemoglobin concentrations were higher if the patient presented a co-morbidity factor. Ninety-three percent of pre-transfusion and 79% of discharge haemoglobin concentrations are in accordance with the guidelines. According to the physicians, the RBC transfusions are too "precocious" when pre-transfusion haemoglobin concentration is above nine and the anaemia is asymptomatic. 50% of RBC transfusion with discharge haemoglobin concentration above 10 is not excessive. In case of acute anaemia, the pre-transfusion and discharge haemoglobin concentrations are higher and RBC transfusion excessive. In this study, the trigger haemoglobin concentration is "restrictive", but the target haemoglobin concentration is "liberal" with a high-discharge haemoglobin concentration. Inappropriate RBC transfusions are mainly due to over-transfusion.

Desmopressin is not always effective in mild haemophilia A patients undergoing urological surgery: the need of standardized protocols.

Desmopressin may be an efficient haemostatic treatment for mild A haemophiliacs because its infusion raises plasma factor VIII level. We report the use of desmopressin in five mild haemophilia A patients undergoing urological surgery. They all received a preoperative infusion (0.3 microg kg(-1), i.v.) 1 h before incision followed by repeated injections at 12- or 24-h intervals according to the severity of the procedure. Nevertheless, four patients presented a postoperative bleeding requiring again surgery performed for 3 of them under clotting factor concentrate instead of desmopressin. The occurrence of haemorrhage was not always correlated with particularly low plasma factor VIII level. Surgical management of urological procedures with desmopressin in mild haemophilia A patients requires standardized protocols.