TARP as immunotherapeutic target in AML expressed in the LSC compartment

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Lacosamide monotherapy in clinical practice: A retrospective chart review

Objective: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Materials and Methods: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). Results: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). Conclusions: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizuresThis study was supported by UCB Pharm

Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1

Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype. PED was characterized by choreoathetosis, dystonia or both, affecting mainly the legs. Predominant epileptic seizure types were primary generalized. A median CSF/blood glucose ratio of 0.52 (normal >0.60) in the patients and a reduced glucose uptake by mutated transporters compared with the wild-type as determined in Xenopus oocytes confirmed a pathogenic role of these mutations. Functional imaging studies implicated alterations in glucose metabolism in the corticostriate pathways in the pathophysiology of PED and in the frontal lobe cortex in the pathophysiology of epileptic seizures. Three patients were successfully treated with a ketogenic diet. In conclusion, co-occurring PED and epilepsy can be due to autosomal dominant heterozygous SLC2A1 mutations, expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for this clinical syndrome

Neonatal screening improves sickle cell disease clinical outcome in Belgium.

Objectives To compare the outcomes of sickle cell disease patients diagnosed through neonatal screening with those who were not. Methods In an observational multicenter study in Belgium, 167 screened and 93 unscreened sickle cell disease patients were analyzed for a total of 1116 and 958 patient-years of follow-up, respectively. Both groups were compared with propensity score analysis, with patients matched on three covariates (gender, genotype, and central Africa origin). Bonferroni correction was applied for all comparisons. Results Kaplan-Meier estimates of survival without bacteremia were significantly higher in the screened group than the unscreened group (94.47%; [95% CI, 88.64-97.36%] versus 83.78% [95% CI, 72.27-90.42%]), p = 0.032. Non-significant differences between both groups were reported for survival without acute chest syndrome, acute anemia, cerebral complication, severe infection, and vaso-occlusive crisis. Significantly lower hospitalization rate and days per 100 patient-years were observed in the screened compared with the unscreened group (0.27 vs. 0.63 and 1.25 vs. 2.82, p = 0.0006 and <0.0001). Conclusion These data confirm the benefit of a neonatal screening programme in reducing bacteremia and hospitalization

Les complications respiratoires de la drépanocytose chez les enfants: le syndrome thoracique aigu.

The acute chest syndrome (ACS) is one of the most frequent complications of sickle cell disease. It affects mostly young children and counts for one quarter of mortality in the young sickle cell disease (SCD) population. This retrospective study evaluates the impact of ACS among hospitalizations for other complications of SCD in patients at the University Childrens' Hospital Reine Fabiola (Brussels, Belgium) in order to isolate clinical conditions associated with a high risk of ACS development. The medical records of all SCD patients aged up to 18 years admitted for all SCD related acute complications over a period of 13 month have been reviewed. Two patient groups have been formed based on the presence of an ACS within the study period. Epidemiologic data, medical history, the clinical presentation at admission but also blood counts in steady state, at admission and along the hospital stay were compared for a total of 96 hospital stays. There is no difference for age or hemoglobin phenotype between the two major patient groups. Male sex and having had a previous ACS episode in the past were significantly more important in the group of patients hospitalized for ACS. Thoracic pain in an SCD patient who doesn't show typical ACS symptoms should be interpreted as a risk factor for ACS. In conclusion, male sex, medical history of at least one ACS and thoracic pain at hospital admission are associated with high risk of developing ACS.English AbstractJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe