Ultrasound arterial anomalies in patients exposed to nilotinib therapy for chronic myeloid leukemia.

INTRODUCTION: Patients exposed to nilotinib for chronic myeloid leukemia (CML) appear to be at risk of arterial complication. The prevalence and aspect of ultrasound asymptomatic arterial lesions are unknown. OBJECTIVE: To describe prevalence and characteristics of ultrasound arterial anomalies in patients treated with nilotinib for CML. METHODS: Patients treated with nilotinib from 2006 to 2015 in the department of the Paoli-Calmettes Institute, Marseille, were included retrospectively. A vascular ultrasound screening was carried out from 2010. The arterial lesions at the first examination were described: plaque and its echogenicity, stenosis or occlusion. A vascular arterial anomaly (VAA) was defined by the presence of a clinical and/or ultrasound anomaly. Patients with or without VAA at initial vascular examination were compared using bivariate and multivariate analysis. RESULTS: 74 patients were included (51.4% men, mean age 54.5 years); 25 patients had ultrasound arterial anomalies (33.8%). Carotid bulb was the most involved territory (44%). Arterial anomalies were: 88% plaques, 44%>50% stenosis and 12% occlusion. 72.7% plaques were echolucent or hypoechogenic. A VAA was present in 25 patients with initial vascular evaluation (33.8%). Patients with VAA at baseline were significantly older (64.9 vs 49.3, P<0.001), older at nilotinib initiation (60.8 vs 46.5, P<0.001), with more arterial hypertension (40% vs 12.2%, P=0.01), with more cardiovascular risk factors (P=0.03). In patient with no cardiovascular risk factor 12.5% had VAA (n=24). CONCLUSION: Nilotinib seems to be associated to arterial lesions of unstable lipid-like appearance. The most involved arterial territory was the carotid bulb and the most common lesion was echolucent or hypoechogenic plaque. VAA can occur in patients without cardiovascular risk factors. This result encourages us to systematically screen and follow all patients exposed to nilotinib even those without cardiovascular risk factors.

Descriptive study of the general practitioners' perception of direct oral anticoagulants and the risk of genital bleeding in women of childbearing age.

AIM OF THE STUDY AND PATIENTS: Direct oral anticoagulants (DOA) tend to replace antivitamins K (VKA). The incidence of major and minor hemorrhages is higher in women, a difference potentially linked to genital hemorrhages. The objective is to assess the practices and perception of general practitioners of the use of oral anticoagulant therapy in women of childbearing age. MATERIALS AND METHODS: Descriptive, observational, transversal and monocentric study. An 11-items questionnaire was sent to 900 randomized general practitioners, assessing the type of patient, the type of anticoagulant prescribed, the management of genital bleeding, and the assessment of the quality of life of anticoagulated patients. RESULTS: DOA were the most prescribed anticoagulants. Genital hemorrhage was the second leading cause of minor hemorrhage. Most doctors (60.6%) believed they were due to VKAs. 25% reported an alteration in the quality of life of patients following these genital hemorrhages and 47.5% addressed this subject in consultation. CONCLUSION: Our study suggests that, according to the general practitioners interviewed, genital hemorrhage is more frequent on VKA than on DOA in women of reproductive age, which is contradictory with the data in the literature. The probably taboo subject is rarely mentioned in consultation and is responsible for a deterioration in the quality of life in these young patients. No recommendation exists on the management of this type of genital hemorrhage in these women. An algorithm is proposed for their management.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Clozapine augments delta, theta, and right frontal EEG alpha power in schizophrenic patients.

Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4-3.6 Hz), theta (4.2-7.8 Hz), alpha (8.2-11.8 Hz), beta1 (12.2-15.8 Hz), beta2 (16.2-19.8 Hz), and beta3 (20.2-23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Demyelinating sensorimotor polyneuropathy associated with the use of sirolimus: a case report.

Liver transplantation is associated with a number of neurological complications. We herein report a case of chronic inflammatory demyelinating polyneuropathy associated with the use of sirolimus-based immunosuppression. The patient was treated by converting the immunosuppression from sirolimus to cyclosporine and by a short course of oral steroids. Following this, we observed almost complete clinical and electrophysiologic resolution of this syndrome. We believe that this is the first described case of such a complication occurring in association with sirolimus. This immunosuppressive agent can, therefore, lead to neurological complications similar to the ones that have been observed with calcineurin inhibitors.

Mechanical circulatory assistance in myocardial infarction with refractory cardiogenic shock: clinical experience in 10 patients at a teaching hospital in Rouen.

BACKGROUND: In patients with acute myocardial infarction (MI), cardiogenic shock (CS) remains associated with a high mortality (close to 50%) despite optimal therapeutic strategy. For those patients who are unlikely to survive, mechanical circulatory support (MCS) might be an additional life saving strategy. OBJECTIVE: To evaluate the efficacy of circulatory assistance in myocardial infarction complicated by cardiogenic shock. METHODS: We retrospectively studied the characteristics and clinical outcome of 10 patients hospitalized with acute MI and CS who required MCS. Mean age was 52+/-8 years; location of MI was anterior in 80% of cases. Immediate coronary angiography was performed in all cases 5.8+/-7.0 hours from the onset of symptoms. Intra-aortic balloon pumping was used in 70% of patients and 30% received thrombolysis. Angioplasty with stent implantation was performed in 8 patients. RESULTS: In all patients MCS was placed within a mean of 57+/-92 hours after admission for hemodynamic instability (systolic aortic pressure: 85+/-13 mmHg; mean: 64+/-10 mmHg). Extracorporeal membrane oxygenation (ECMO) was implanted in 8 patients followed by Thoratec in one. The other 2 patients received a Thoratec and a Heartmate II system respectively. Survival rate was 40% (4 patients): 3 patients underwent heart transplantation at a mean of 93+/-97 days and one patient is alive with definitive implantable Heartmate. The other six patients died in hospital. CONCLUSION: Mechanical circulatory support appeared life saving in 4 out of 10 patients with acute MI and cardiogenic shock refractory to optimal treatment. In this situation, circulatory assistance deserves discussion and the choice of optimal device should be further evaluated.

[Revascularisation of unprotected left main coronary artery disease: an update]. / Revascularisation du tronc commun coronaire gauche non protégé.

Coronary bypass grafting is the reference treatment of unprotected left main coronary disease. Nevertheless, the experience of invasive cardiologists and the introduction of active stents make angioplasty possible in selected cases. Only the results of controlled clinical trials (SYNTAX trial currently under way) will enable physicians to choose the most appropriate method of revascularisation for their patients.

[Aortic bioprosthesis implanted percutaneously: three year follow up]. / Bioprothèse aortique implantée par voie percutanée: suivi à trois ans.

Percutaneous implantation of a bioprosthesis for the treatment of degenerative aortic stenosis ushered in a new era for interventional cardiology, and now represents the best therapeutic option for a growing number of patients for whom surgical aortic replacement would be too risky. This is the case in about a third of symptomatic patients affected. Between 2003 and 2005, we performed initial feasibility studies (I-REVIVE and RECAST) in Rouen, on non-operable patients in a critical state, included for purely compassionate reasons. The valve used was a pericardial bioprosthesis mounted in an expandable balloon stent. The mean age of the patients was 80 years, all had multiple co-morbidity and had been turned down by the cardiac surgeons. In 33 of the 36 included patients, the technique was attempted by the anterograde trans-septal approach (n=27, success rate 80%) or by the retrograde arterial route (n=7, success rate 57%). Echocardiography following implantation revealed a final aortic surface area of 1.70 cm2 and a transvalvular gradient of 9 mmHg. A significant paravalvular aortic leak was noted in 5 cases. There were 6 deaths by 1 month, related to the procedure, and 10 deaths by 6 months, from non-cardiac causes and not related to the procedure. There was no occurrence of coronary occlusion, secondary displacement or dysfunction of the prosthesis. In December 2006, 8 patients reached 2 years of follow up, and two others reached 3 years, symptom free and still with an unchanged valvular function. Significant technological improvements have made the technique simpler, quicker and safer, with very much improved short and long term results. The new trans-apical approach is under evaluation with some promising initial results. More than 280 patients have been implanted to date. Other implantable prostheses are under evaluation. This therapeutic modality looks likely to develop rapidly, and in the near future it should offer a new and optimal solution for all high surgical risk or non-operable patients.

A founder haplotype for autosomal dominant sensory ataxia in Eastern Canada.

We present phenotypic and genotypic data for an additional family with autosomal dominant sensory ataxia, a disease characterized by gait difficulties associated with diminished sensation in the limbs and areflexia. The same disease haplotype spanning the entire SNAX1 locus is observed in affected members of this second family, enabling the locus to be reduced to a 7.3-cM interval.

The Paced Auditory Serial Addition Test: to what extent is it performed as instructed, and is it associated with disease course?

One commonly used outcome measure in multiple sclerosis (MS) clinical trials is the Multiple Sclerosis Functional Composite, which includes the Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive function. Concerns have been raised about the standard PASAT scoring method, whereby the number of correct responses is summed. This method does not take into account whether the test is performed as intended, which may affect interpretation of the results. Accordingly, another scoring method has been proposed, which examines the number of times a correct response is immediately preceded by another correct response (termed a dyad). We compared the two scoring methods for the PASAT, and found that the mean percentage of correct responses not accounted for by dyads ranged from 27.5% to 49.5%, indicating that much of the time the test is not performed as instructed. We also examined disease course and the PASAT score, as studies have produced conflicting results as to whether disease course is associated with cognitive impairment. Although disease course was significantly associated with the PASAT score, it accounted for little of the variation in scores, even when adjusting for other predictors. Finally, as 14.2% of participants refused to do the PASAT or failed to complete it, we also examined whether the Perceived Deficits Questionnaire (PDQ), a self-reported measure of cognitive function, is a potential proxy measure for the PASAT. The correlation between the two tools was low (-0.14), suggesting that the PDQ is not a useful substitute for the PASAT.

Water and soil pollution in vineyards of central Thailand.

Very intensive cultivation systems have been developed in the delta of the Chao Phraya River for about a century. The objective of the study was to determine the fate of the fertilisers and pesticides applied to vineyards grown on raised beds. Water samples were collected from the outlet of a vineyard to determine the discharge of pollutants in the canal. The accumulation of elements in the soil was investigated by analysing soil samples from different fields. Fertilisation was estimated at 670 kg N, 300 kg P, and 560 kg K year(-1) ha(-1). Insecticides and fungicides were applied every four days on average, using up to 23 different molecules. Little N and no P were discharged in the canals in solution and discharge in suspension was minor. Pesticides were detected in 36% of the water samples. The topsoil contained 1600 mg kg(-1) Bray II P, 936 mg kg(-1) exchangeable K, 170 mg kg(-1) total Cu, and 167 mg kg(-1) total Zn. Pesticides were detected in 62% of the fruits after peeling. Overuse of fertilisers did not lead to water pollution, but overuse of pesticides resulted in pollution of the water bodies and of the fruits. Most applied elements accumulated in the soil, resulting in high values of P, K, Cu, and Zn.

Genetic susceptibility to MS: a second stage analysis in Canadian MS families.

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Characteristics of responders and nonresponders to brief-pulse right unilateral ECT in a controlled clinical trial.

In a double-blind, randomized controlled study of electroconvulsive therapy (ECT) in patients with major depression, 7 of the 17 patients allocated to the right unilateral group failed to respond to treatment. The nonresponders were subsequently openly treated with bitemporal treatment, which produced an acceptable outcome in these cases of right unilateral treatment failure. This paper describes the clinical outcome, electrophysiological characteristics (impedence, estimated seizure threshold, and change in threshold), and the degree to which stimuli exceeded threshold in the responder and nonresponder groups. Responders had lower seizure thresholds and longer seizures than nonresponders. In comparison with nonresponders, responders showed trends toward greater impedance and treatment at a somewhat greater degree above threshold during the first few treatments. Threshold change with treatment was found not to be related to clinical outcome. Early identification of patients likely to respond to low-dose right unilateral ECT, together with the avoidance of benzodiazepine prescription during ECT, may permit many patients to receive low-dose right unilateral ECT successfully and with a minimum of cognitive impairment.

Regional access to acute ischemic stroke intervention.

BACKGROUND AND PURPOSE: Benefit-risk ratios from recombinant tissue plasminogen activator (rtPA) therapy for acute ischemic stroke demonstrate lack of efficacy if intravenous administration is commenced beyond 3 hours of symptom onset. We undertook to enhance therapeutic effectiveness by ensuring equitable access to rtPA for patients affected by acute ischemic stroke within a 20 000 km(2) population referral base served by a tertiary facility. METHODS: Representatives of all provider groups involved in emergency medical services developed a Regional Acute Stroke Protocol (RASP), a coordinated regional system response by dispatch personnel, paramedics, physicians, community service providers, emergency and inpatient staff in community hospitals, and the tertiary facility acute stroke team. RESULTS: As of July 26, 1999, all ambulance services in Southeastern Ontario began bypassing the closest hospital to deliver patients meeting the criteria for the RASP to the Kingston General Hospital. At 12 months, approximately 403 ischemic strokes have occurred in the region, the RASP has been activated 191 times, and 42 patients have received rtPA. CONCLUSIONS: We conclude that (1) acute stroke patients in Southeastern Ontario have improved access to interventions for stroke care; (2) geography of the region is not a barrier to access to interventions for patients with acute stroke; and (3) acute ischemic stroke patients treated with rtPA account for 5% of all acute strokes and 10% of all ischemic strokes in this region.