Sex-specific risk factors for recurrent venous thromboembolism

Background

Men have higher risk of recurrent venous thromboembolism (VTE) than women but this sex difference remains unexplained. In addition, whether men and women share same risk factors for recurrent VTE is unclear.

Methods

In a prospective cohort study, 583 patients (234 men and 349 women) aged 18 to 90, with a first idiopathic VTE, were followed for an average of 28 months. We assessed the association between baseline characteristics and VTE recurrence by gender.

Results

Recurrent VTE occurred in 38 women and 36 men (incidence = 4.6% and 7.5% per year respectively; HR = 1.6; 95% CI, 1.0-2.6). This relation between sex and recurrent VTE was more pronounced in patients younger than 50 years and in the presence of factor V Leiden (FVL) mutation. Multivariate analyses showed that obesity (HR, 2.8 (95% CI, 1.3-6.0)) and aging (HR, 1.3 (95% CI, 1.1-1.4) per 10 years increase) were related to an increased risk of recurrent VTE in women while FVL mutation (HR, 3.5 (95% CI, 1.5-8.1)) was a risk factor of recurrent VTE among men.

Conclusion

Men and women do not share the same risk factors for recurrent VTE. Consequently, gender has to be taken into account to improve the risk stratification and prevention of VTE recurrence.     

Neurodevelopment of children born very preterm and free of severe disabilities: the Nord‐Pas de Calais Epipage cohort study

Aim: To describe the development of very preterm children free of cerebral palsy or severe sensory impairment in the domains of gross and fine motor functions, language and sociability at a corrected age of 2 years; to identify factors associated with performances in each domain. Methods: A total of 347 children born in 1997 before 33 weeks of gestation, part of the EPIPAGE population‐based cohort study, had their psychomotor development assessed with the Brunet‐Lezine scale. Results: The study population had a mean gestational age of 30.1 ± 2.0 weeks. Lower developmental quotients (DQ) were observed in the study group compared to the reference sample (96 ± 13 vs 104 ± 8, p < 0.01). Fine motor function, language and sociability were all affected with a p value <0.01. Multivariate analysis showed that duration of intubation and parents’ educational and occupational levels were the only variables significantly related to each developmental domain (p < 0.01). Conclusions: Children very preterm and free of severe disabilities had mild delays in multiple areas of development. The mechanisms by which neonatal factors played a role need further investigation. However socioeconomic status had a great impact on development and our results underline the need for improved support of socioeconomically disadvantaged parents after a preterm birth.     

Plasma fibrinogen explains much of the difference in risk of coronary heart disease between France and Northern Ireland. The PRIME study

The incidence of coronary heart disease is higher in Northern Ireland than in France. These differences have not been adequately explained. We have investigated the associations of plasma fibrinogen concentration and factor VII activity with the incidence of coronary heart disease in a prospective cohort study involving 10600 men aged 50-59 living in four regions (Lille, Strasbourg, and Toulouse in France, Belfast in Northern Ireland). Baseline fibrinogen and factor VII were measured in 9489 men free of coronary heart disease at entry (7167 in France and 2322 in Northern Ireland). Over 5 years of follow-up, 161 participants developed myocardial infarction (MI) or coronary death (100 in France and 61 in Belfast) and 151 developed angina pectoris (94 in France and 57 in Belfast). The risk of future coronary events was 1.9 times higher in Belfast than in France (95% confidence interval: 1.5-2.4). Baseline mean levels of fibrinogen were significantly higher in Belfast than in France and they were higher in participants who experienced coronary events compared with those who did not in both countries. The age-adjusted relative risk of coronary heart disease associated with a rise of one standard deviation in fibrinogen level was 1.56 (95% confidence interval: 1.29-1.95, P<0.0001) in the whole cohort. This association remained significant after adjustment for other cardiovascular risk factors (relative risk:1.36; 95% confidence interval: 1.14-1.68; P<0.0001). There was no clear geographical variation in factor VII and no significant association between factor VII levels and the risk of coronary events was observed. Classic risk factors explained 25% of the excess risk of coronary heart disease in Belfast compared with France, while fibrinogen alone accounted for 30%. These findings add to the epidemiological evidence that elevated fibrinogen is a major risk factor for coronary heart disease.     

Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men

ObjectiveCXCL16 is a chemokine involved in atherosclerosis by promoting inflammation, lipid accumulation and matrix degradation. The level of circulating CXCL16 has been proposed as a predictor of long-term mortality in acute coronary syndromes. We studied plasma CXCL16 in acute ischemic stroke and examined associations with long-term mortality following the acute event.MethodsCXCL16 samples were obtained from 244 patients with acute ischemic stroke (age: 69 ± 13 years) daily from presentation to day 5 and at half a year after the stroke. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all-cause and cardiovascular (CV) mortality as end-points.ResultsAt follow-up, 72 patients had died with 43 due to CV causes. Plasma CXCL16 was stably elevated in the first days after the acute event followed by a marked decrease after 6 months. In patients who subsequently suffered an adverse outcome, CXCL16 levels at 4 days after the initial event were elevated and were moderately associated with mortality. The increase in CXCL16 from day 1 to 4 was a predictor for all-cause and, in particular, CV mortality even after adjustment in the multivariate analysis for established risk factors such as age, the presence of heart/renal failure, troponin, C-reactive protein and stroke severity.ConclusionsAn increase in plasma CXCL16 during the first days after the initial event is associated with an adverse outcome in patients with acute ischemic stroke, supporting the potential pathogenic role of CXCL16 in atherosclerosis and vascular remodelling as well as their major clinical consequences.     

Brain volumes in late life: gender,hormone treatment,and estrogen receptor variants

Structural imaging studies suggest gender differences in brain volumes; however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippocampal volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippocampal and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.     

Deformability and intrinsic material properties of neonatal red blood cells

Whole cell and membrane deformability are essential for red blood cell (RBC) survival and for effective blood flow. Neonatal RBCs display several specific properties (eg, large size, high hemoglobin F) that could influence their deformation characteristics and contribute to their shortened life span. The present study was designed to compare selected rheologic properties (cellular deformability, pressure required to aspirate RBC into micropipettes, static and dynamic viscoelastic material properties) of neonatal and adult RBCs. RBC deformability, as studied by a rheoscope, was similar for neonates and adults over a shear stress range of 2.5 to 500 dyn/cm2. The pressure required to aspirate RBCs completely into 3.3-micron diameter pipettes was 129 +/- 87 dyn/cm2 for neonatal RBCs and 71 +/- 37 dyn/cm2 for adult RBCs. The aspiration pressure for neonatal and adult RBCs increased with increasing RBC volume, suggesting that the increased mean aspiration pressure for neonatal RBCs resulted from their larger volume. When RBCs with same volume and diameter were compared, the aspiration pressure tended to be smaller for neonatal RBCs than for adult cells. To characterize material properties determining RBC deformability, we measured membrane extensional (shear) and bending elastic moduli, the time constant for elastic recovery from extensional deformation and hemoglobin viscosity (ie, cytoplasmic viscosity) of neonatal and adult RBCs. Membrane surface viscosity and time constant for recovery from bending deformation were calculated. The extensional and bending moduli of neonatal RBCs were slightly smaller (10% and 16%, respectively) compared with adult cells. This suggests that the static resistance of neonatal RBC membrane to deformation and failure in response to a given force is slightly smaller. The time constant for recovery from extensional deformation of neonatal RBCs was larger by 14%, compared with adult cells. The time constant for bending deformation related to the RBC diameter and surface area was increased by 18% in the neonates. Membrane surface viscosity and hemoglobin viscosity were similar for both cell types. These results indicate that the deformability and viscoelastic properties of neonatal RBCs deviate only slightly from those of adult RBCs and that the increased aspiration pressure of neonatal RBCs is solely due to their large size. Some of the specific deformation characteristics observed in this study (increased aspiration pressure, decreased resistance to elastic deformation) may contribute to the shortened life span of neonatal RBCs.     

Iatrogenic subcutaneous facial emphysema secondary to a Class V dental restoration: a case report

Subcutaneous facial emphysema (SFE) following routine dental operative procedure is an uncommon but potentially life‐threatening complication. The present case details a Class V restoration where air was introduced into the fascial tissue planes via the gingival sulcus from the use of an air‐driven dental handpiece. Although the SFE is usually self‐limiting within 3–10 days, such instances should be regarded as a medical emergency as in severe cases, the air may spread to the neck, mediastinum and thorax to result in cervicofacial emphysema with potential pneumomediastinum and pneumothorax.     

Subjective signs in premotor epilepsy: confirmation by stereo-electroencephalography.

Subjective manifestations inaugurating frontal seizures are less well known than those observed in temporal seizures. We report eleven consecutive patients who underwent surgery for premotor epilepsy. Six of them had focal cortical dysplasia. Ictal symptomatology was analysed to establish electroclinical correlations. The localisation of the epileptogenic zone was assessed by stereoelectroencephalographic studies. Subjective manifestations were described in all cases, more frequently in a sensory rather than an emotional or psychological fashion. Focal seizures limited to subjective features were recorded in two patients. In one, psychological illusions and visual hallucinations were related to the superior frontal sulcus. Another presented isolated paraesthesia in the left arm with the implication of the supplementary motor area. Electrical stimulation of an electrode located in the premotor area evoked isolated subjective manifestations in three other patients. One patient reported sensory manifestations and another, ideational manifestations. Cephalic sensations and emotional manifestations were associated in one case. Subjective manifestations were observed in all patients, and were proved to be related to a discharge restricted to the premotor area in five. These were non-specific signs, but were always the same in a given patient. Spontaneous, isolated sensations and stimulation data tended to be contradictory. This illustrates the complexity of analyzing subjective signs, as well as the complexity of the neuronal networks participating in the propagation of discharges arising in the premotor frontal area.