Anticoagulant activity and pleiotropic effects of heparin.

The recognized therapeutic effect of heparins is an anticoagulant activity (anti-Xa and anti-IIa) acting in an indirect manner (cofactor of antithrombin) but which is carried by only 20% at best of the glycan chains composing any commercial preparation of heparin, whether unfractionated or low molecular weight. However, the effects of glycan chains that participate in the therapeutic but also potentially adverse effects of heparin preparations must also be considered. These specific effects of glycans are potentially different for each commercial preparation of heparins and, in particular, low molecular weight heparins (LMWH) compared with unfractionated heparin (UFH) and LMWH between them. The glycanic nature of heparin is responsible for its very particular pharmacology: exchange with the glycocalyx of cells in particular endothelial. Exchanges which depend on the length and structure of the glycan chains therefore different between UFH and LMWH between the different heparin preparations between them but also according to the state of glycocalyx differently altered according to the underlying diseases and their degree of evolution. If the anticoagulant effects of heparins can potentially be replaced with those of new oral anticoagulants, the glycan effects of heparins cannot be replaced by synthetic non-glycan molecules. This replacement will undoubtedly limit certain risks such as heparin-induced thrombocytopenia (HIT) but other beneficial effects participating to the overall efficacy of heparin (whose relative importance remains to be ascertained), will also disappear: effects on surfaces, anti-inflammatory effects, antineoplastic and anti-metastatic effects, ancillary anticoagulant effects (not dependent on antithrombin), effect on endothelial dysfunction. This review will be focused on all of these related/pleiotropic effects of heparins that are in fact the effects of the glycan nature of heparin. Among the antithrombotic effects not dependent on antithrombin one has been more recently highlighted: the passivation/neutralization of the positively charged fibrils of Netosis, by the negatively charged glycan chains of heparin. This also has clinical implications: in the era of generics and biosimilars where biosimilar heparins begin to appear, it is important to know that accordingly to FDA and EMEA rules: their biosimilarity is judged only on the "classical" anticoagulation effect cofactor of antithrombin (anti-IIa/anti-Xa) but that all glycan effects that are potentially beneficial or potentially deleterious are not taken into consideration in their assessment.

Determinants of aspirin resistance in patients with type 2 diabetes.

BACKGROUND: Cardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin. METHODS: Included were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated. RESULTS: Using LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2. CONCLUSION: Our results reveal that 'aspirin resistance' is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.

[Ear aid in Myanmar]. / Ohrenhilfe in Myanmar.

As the example of a small team working in Myanmar since 2010 has demonstrated, it is possible to achieve sustainable success in medical education and training in foreign countries with relatively little effort, in this case in middle ear surgery. The main requirements are outstanding communication within the team as well as with the authorities, organizations, and colleagues on site. Equally important is mindful and respectful work in the hosting country and the consideration of cultural particularities. Essential contributing factors for long-term success are intercultural exchange, interpersonal relationships, and especially the motivation of colleagues on site, which together create a foundation of trust. This trust combined with regular exchange visits enables constant professional development according to the current needs.

[ST elevation myocardial infarction in young adults: Is there an interest for thrombophilia screening?] / Syndrome coronarien aigu avec sus-décalage du segment ST chez les jeunes adultes : le bilan de thrombophilie a-t-il un intérêt ?

BACKGROUND: Coronary lesions characteristics as well as patient thrombogenicity can explain coronary events manifestation. In young patient, local conditions are usually less important and thrombogenicity could play a significant role. Assessing thrombophilia could be justified in young patients and may induce an adapted therapeutic management. PURPOSE: We aimed to assess the prevalence of thrombophilia and therapeutic modification in young adults aged≤55 years admitted in our department for ST elevation myocardial infarction (STEMI). METHODS: From January 2013 to January 2017, data on all patients aged≤55 years with STEMI admitted in emergency were retrospectively retrieved from our database. Thrombophilia investigation was made regarding clinical (with or without cardiovascular risk factors [CVRF]), biological and/or angiographic evaluation. RESULTS: A total of 133 patients aged≤55 years with STEMI were included. Cardiac arrest occurred in 15 patients (11%). One or less CVRF were found in 47 patients (35%). Smoking was reported in 93 patients (70%) and drug addiction (cannabis, cocaine) in 19 patients (14%). A subset of 51 patients (38%) were screened for thrombophilia. Patients with thrombophilia assessment were younger, less active smokers and presented less CVRF than patients without investigation (P<0.001). Single vessel diseased was found in 88 patients (66%). No differences regarding coronary procedural characteristic were found between the two groups. The most frequently encountered aetiology, found in 122 patients (92%), was de novo intra-arterial thrombosis related to atherosclerosis. In patients with thrombophilia assessment (n=51), one or more abnormal biological results was found in 22 patients (43%) and a therapeutic adjustment was made in 6 patients (12%). CONCLUSION: Thrombophilia screening in young STEMI adults showed an abnormality in 43% of cases. Antithrombotic treatment can be modified after its demonstration.

Prognostic value of plasma B-type natriuretic peptide in patients with severe cardiotoxic drug poisoning.

BACKGROUND/OBJECTIVES: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. METHODS: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. RESULTS: While BNP values on admission were poorly informative, subsequent BNP measurements (11 ± 6 h after admission) were significantly increased in patients with CS compared to those with non-CS (756; [364-1130] versus 24; [15-65] pg/ml respectively; P = 0.008). This second BNP level was also significantly increased in non-survivor patients compared to survivor patients (784; [654-1028] versus 29; [15-104] pg/ml respectively; P = 0.05): BNP levels above 360 pg/ml predicted in-hospital mortality (sensitivity = 100%, specificity = 92%). In a multivariate analysis, BNP, SAPS II score and lactate blood level were associated with death. CONCLUSIONS: Serial BNP measurements after admission for cardiotoxic drug poisoning are useful to identify patients at the highest risk of CS as well as in-hospital death.

Thoracic aortic disease: evaluation using a single MRA volume series.

OBJECTIVE: Use of MRA for thoracic aortic disease (TAD) evaluation has been limited. This report describes an initial experience with TAD evaluation using a single MRA volume series. MATERIALS AND METHODS: A single volume series, based on sequential 2D TOF MRA, was acquired in 30 cases (28 with suspected TAD and 2 normals). Each series was processed using multiplanar reconstruction (MPR) and maximum intensity projection (MIP); resulting tomographic (one base and two MPR) and MIP sets were blindly interpreted by four reviewers to detect TAD and, if present, to diagnose its specific form. For cases incorrectly interpreted, the standard MR images were subsequently interpreted. RESULTS: The TAD categories included aneurysm (n = 13), dissection (n = 9), and arch anomalies (n = 5). Sensitivities were high for TAD overall (89-100%) and TAD in ascending and descending portions; sensitivities were lower for TAD of the arch (two of four reviewers > or = 90% for TAD overall and descending TAD). Specificities for TAD overall had a wider range (67-100%), but were high for ascending, arch, and descending portions (three to four of four reviewers > or = 90% for each). Sensitivities for aneurysms (69-92%) and dissections overall (67-100%) were comparable, as they were in ascending and arch portions; descending dissection was better detected than descending aneurysm (two of four reviewers > or = 90% for ascending or arch aneurysm and for descending dissection); overall specificities (88-100 vs. 81-95%) and specificities in ascending, arch, and descending portions were also comparable (three to four of four reviewers > or = 90% for both in each portion; two of four reviewers > or = 90% for dissection overall). Each reviewer achieved > or = 70% diagnostic accuracy for TAD (one of four reviewers = 85%); accuracies for each category were comparable. Interpretation of standard MR images corrected all detection and most diagnostic (> or = 63%) errors. CONCLUSION: This initial experience with conventional TOF MRA for TAD evaluation is encouraging, but it indicates the potential for advancements in data acquisition and/or postprocessing.

Pulse sequence strategies for vascular contrast in time-of-flight carotid MR angiography.

A systematic evaluation in healthy volunteers of the relative efficacy of various techniques for background suppression to improve two-dimensional (2D) and three-dimensional (3D) time-of-flight magnetic resonance angiography of the cervical carotid arteries was performed. Conventional 2D and 3D FISP (fast imaging with steady-state precession) sequences with flow compensation were compared with modifications of these sequences, including a tracking saturation pulse (2D), prolonged absolute TEs for fat suppression based on T2* decay (2D and 3D), frequency-selective saturation of fat (2D and 3D), in-plane spatial saturation (2D), and magnetization transfer contrast (2D and 3D). The tracking saturation pulse and slight overlap of the excitation sections provided uniform background suppression without impairing depiction of the morphology of the cervical carotid arteries. Frequency-selective fat saturation was the most effective background suppression scheme among the 2D and 3D techniques but was occasionally compromised by local field inhomogeneities. Magnetization transfer contrast provided little suppression of stationary tissues in the neck because of the intrinsic limitations of the coil. In-plane spatial saturation yielded the highest background suppression but reduced apparent arterial diameters and could not be implemented in a 3D version. The T2* decay method not only reduced the apparent size of the vessels but also their signal intensity.

Lumbar degenerative disk disease: prospective comparison of conventional T2-weighted spin-echo imaging and T2-weighted rapid acquisition relaxation-enhanced imaging.

PURPOSE: To compare conventional T2-weighted spin-echo imaging with a rapid acquisition relaxation enhanced (RARE) technique in the routine evaluation of lumbar degenerative disk disease. METHODS: Thirty consecutive patients referred for evaluation of the lumbar spine for suspected degenerative disk disease were evaluated with sagittal and axial T1-weighted spin-echo, conventional T2-weighted spin-echo, and T2-weighted RARE "turbo spin-echo" sequences (4000/93/2 (repetition time/echo time/excitations), 192 x 256, echo train length of 8). Conventional T2-weighted and RARE images were evaluated independently by two neuroradiologists for image quality, presence of artifacts, cerebrospinal fluid signal intensity, extradural interface conspicuity, intradural nerve root conspicuity, soft-tissue detail, and signal intensity of normal and degenerated intervertebral disks. RESULTS: Both readers rated the cerebrospinal fluid signal higher, the extradural interface conspicuity higher, and the nerve root detail greater on the turbo spin-echo than on conventional spin-echo images. Neither reader had a significant difference in ranking "normal" or "degenerated" disk signal on the two sequences. Both readers rated soft-tissue detail higher for conventional than for turbo spin-echo. CONCLUSION: RARE sequences can replace conventional T2-weighted spin-echo sagittal studies for degenerative lumbar disk disease.

Three-dimensional time-of-flight MR angiography with a specialized gradient head coil.

A gradient head coil has been developed, incorporating two independent gradients within the conventional body coil of the magnetic resonance (MR) system, with reduced rise times (200 microseconds) and maximum amplitudes of 37 and 18 mT/m in the z and y directions, respectively. This gradient coil was systematically evaluated by testing two-dimensional (2D) and three-dimensional (3D) time-of-flight (TOF) MR angiography sequences applied to a pulsatile flow phantom simulating a carotid stenosis and the intracranial vasculature. When standard 2D and 3D TOF MR angiography techniques were used to image the carotid stenosis model, dramatic signal loss in the stenotic segment and a large flow void distal to the stenosis were seen. The shorter (3.8 msec) absolute echo times (TEs) achievable with the gradient coil in 3D sequences substantially reduced the phase dispersion and associated signal loss in the region of stenosis. Shorter TEs alone (3.2 msec) did not minimize signal loss, and first-order flow compensation in the read and section-select directions provided further improvements (despite slightly longer TEs). Reduction of TEs in 2D sequences yielded relatively poor results regardless of the refocusing scheme or TE. This study confirms the predicted benefits of a dedicated coil with improved gradient capabilities for 3D MR angiography. The study suggests the limitations of 2D TOF MR angiography in the evaluation of severe stenoses.

3D MRI of the cervical spine: low flip angle FISP vs. Gd-DTPA TurboFLASH in degenerative disk disease.

The authors undertook this study to compare bright and dark CSF three-dimensional (3D) gradient-echo (GE) MR techniques to answer the following questions: Could a single Gd-DTPA enhanced T1-weighted GE volume sequence (with multiplanar reformats) be diagnostically equivalent for degenerative cervical disk disease to a standard sequence consisting of sagittal T1-weighted spin echo and axial low flip angle volume GE images (with reformatted images)? Does performing oblique coronal reformats perpendicular to the course of exiting cervical nerve roots improve diagnostic confidence over axial images alone? Thirty-one consecutive patients received a "routine" MR examination consisting of a sagittal T1-weighted spin echo and axial low flip angle volume sequence (FISP) [(35/7/5), 64 slices, 2 mm slice thickness, 192 x 256 matrix, 7.2 min]. Each patient was then given 0.1 mmol/kg Gd-DTPA intravenously, and reimaged with a T1-weighted volume GE sequence [(13/6/12), acquired as 128-1.2 mm coronal partitions, 192 x 256 matrix, 5.5 min]. Sequences were reconstructed on the standard diagnostic console in 1 mm increments. Sets of examinations (routine vs T1-weighted volume) were independently interpreted by three neuroradiologists for location, type, and severity of extradural degenerative disease. There was no strong or consistent trend for increased detection of disease by one imaging sequence over the other. For lateral disk disease, only 3% of the observations were in discordance. For disk disease, there was close agreement in the severity scores. All readers indicated that additional information was provided by the reformatted images more frequently with TurboFLASH (fast low angle shot) than with FISP. All readers indicated that increased confidence was provided by the reformatted images more frequently with TurboFLASH than with FISP. A single 3D contrast-enhanced TurboFLASH sequence is diagnostically equivalent to a set of two-dimensional T1-weighted sagittal spin echo and 3D axial low flip angle sequences for assessing the location and degree of cervical extradural degenerative disease. A screening examination of the cervical spine could be performed with a single contrast-enhanced 5.2 min study, and then relying on computer postprocessing to provide additional imaging planes.

Optimization of three-dimensional T1-weighted gradient-echo imaging of the cervical spine.

Various parameters of the three-dimensional (3D) T1-weighted magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence were evaluated to improve spatial resolution while maintaining T1 contrast and a short examination time in imaging of the cervical spine in volunteers. The most dramatic improvements in image resolution occurred by decreasing section thickness to 1.2 mm and increasing the in-plane matrix to 192 x 256, with a 230-mm field of view. The increase in imaging time due to the increased matrix was offset by the elimination of the preparation pulse and wait time, without dramatic changes in contrast-to-noise ratio or overall image quality. Optimum parameters included elimination of the preparation pulse and wait time, 12 degrees flip angle, 192 x 256 matrix, 1.2-mm section thickness, nonselective excitation (coronal acquisition), RF spoiling, and standard k-space ordering, for an examination time of 5 minutes 21 seconds.

Gd-DTPA-enhanced 3D MR imaging of cervical degenerative disk disease: initial experience.

PURPOSE: To assess whether a single enhanced T1-weighted gradient echo volume sequence, with the appropriate reformatted images, could be equivalent to a more conventional 2D set of MR sequences for the evaluation of cervical extradural degenerative disk disease (bony canal and foraminal stenosis; disk herniation). MATERIALS AND METHODS: Sixty-one patients evaluated for extradural degenerative disease by MR were imaged with a "standard" MR examination (Sagittal T1-weighted spin echo, axial low flip angle gradient echo), were then given 0.1 mmol/kg Gd-DTPA intravenously, and reimaged with either a 3D FLASH (fast low angle shot), TR 40/TE 7/1 excitation), 40 degree flip angle, acquired as 64, 2-mm sagittal partitions, or a 3D turbo FLASH (MP RAGE-magnetization prepared rapid acquisition gradient echo) (10/4/1), 10 degree flip angle acquired as 128, 2-mm coronal partitions. The volume sequences were reconstructed in the axial plane, and right and left 45 degree oblique coronal planes. The two sets of examinations (standard vs volume) were prospectively interpreted by two neuroradiologists for quality of examination, and location, type, and severity of extradural degenerative disease in a random, blinded, independent fashion. RESULTS: There was no significant difference between the standard examination and the 3D MP RAGE for central extradural disease. The 3D FLASH examination was significantly worse than the standard examination in identification of central extradural disease, with an average of 21 herniations not identified, or underestimated in size. Neither the 3D FLASH, nor the 3D MP RAGE examinations showed any significant improvement compared to the routine 2D examination for the location and severity of foraminal disease. CONCLUSION: If extradural degenerative disk disease is being evaluated, then a single enhanced 3D T1-weighted imaging sequence taking 6 minutes can be equivalent to a routine set of mixed 2D spin echo and low flip angle gradient echo sequences.