[Multidisciplinary management of the pediatric sickle cell patient in 2019]. / Prise en charge multidisciplinaire du patient drépanocytaire pédiatrique en 2019.

Sickle cell disease is a common genetic disorder that affects haemoglobin. It is manifested by haemolytic anaemia and vaso-occlusive crisis. It can affect all organs and its evolution is unpredictable. The multidisciplinary management of pediatric patients who suffer from it is essential to adapt their treatment and optimize their evolution. One of the major challenges is to succeed the transition to adult medicine. New therapeutic perspectives are in development and look promising.

La drépanocytose est une maladie génétique fréquente qui affecte l'hémoglobine. Elle se manifeste par une anémie hémolytique et des phénomènes vaso-occlusifs. Elle peut toucher tous les organes et son évolution est imprévisible. La prise en charge multidisciplinaire des patients pédiatriques qui en souffrent est essentielle pour optimaliser leur évolution et adapter leur traitement. Un des défis majeurs est de réussir la transition vers la médecine adulte. De nouvelles perspectives thérapeutiques sont en développement.

[Sweet's syndrome induced by pegfilgrastim during a myelodysplastic syndrome AREB2: A case report]. / Syndrome de Sweet induit par le pegfilgrastim au cours d'un syndrome myélodysplasique AREB2 : à propos d'un cas clinique.

INTRODUCTION: Sweet's syndrome is an acute neutrophilic dermatosis characterized by abrupt onset of skin lesions accompanied by fever, arthralgia, leukocytosis and diffuse neutrophilic infiltration of the dermis, as well as an excellent response to corticosteroid therapy. CASE REPORT: A 46-year-old patient with myelodysplastic syndrome was admitted for chemotherapy. On the eighth day of chemotherapy, he received a single dose of pegfilgrastim. Three days later, he developed pyrexia, conjunctivitis, arthralgia and erythematous and painful papulo-nodular lesions. Broad-spectrum empiric antibiotic therapy was started but the patient's condition deteriorated. Biology showed pancytopenia and inflammatory syndrome. Microbiological tests, autoimmune serologies and chest-computed tomography were negative. Cutaneous biopsy was compatible with Sweet's syndrome. A diagnosis of Sweet's syndrome induced by pegfilgrastim was made and intravenous corticosteroid therapy was started with a rapid favorable outcome. CONCLUSION: Sweet's syndrome is a rare adverse effect of G-CSF.

[Refractory anemias]. / Les anemies réfractaires.

Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

Gefitinib monotherapy in advanced nonsmall cell lung cancer: a large Western community implementation study.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.

[Complementary observational study of the efficacy, tolerance and safety of lansoprazole 15 mg as maintenance therapy of reflux esophagitis in daily medical practice in Belgium (record RU49749/R002]. / Etude casuistique complémentaire de l'efficacité, la tolérance et la sécurité du lansoprazole 15 mg dans le traitement d'entretien de l'oesophagite de reflux en pratique médicale quotidienne en Belgique (record RU49749/R002).

Gastroesophageal reflux disease is a frequent illness with important implications on quality of life. In order to evaluate in a general population the efficacy and safety of lansoprazole 15 mg in maintenance therapy of reflux oesophagitis in current medical practice, an open label observational study was conducted in Belgium. 1.709 patients were included by 429 general practitioners during 3 to 6 months from 1997 to 1999. At the end of the study, symptoms improved or disappeared in 88% of patients. No drug related severe adverse event was reported. This study confirmed that lansoprazole 15 mg is effective and safe in maintenance treatment of reflux oesophagitis.

The prothrombin gene G20210A variant in an unselected thromboembolic population. A Belgian prospective clinical study.

The presence of the 20210A allele of the prothrombin gene has recently been shown to be a risk factor of venous thromboembolism, probably mediated through increased prothrombin levels. The aim of the study was to determine the frequency of the prothrombin 20210A allele in 193 consecutive unselected patients with venous thromboembolism and 100 healthy controls and to analyze the clinical profile associated with this new inherited thrombophilic factor. In agreement with previous reports, we found a frequency of 7.3% of heterozygous carriers of the 20210A allele among patients and 1% among controls. We confirm that plasma prothrombin levels are more elevated in the individuals bearing the prothrombin 20210A allele compared with those who do not. We did not find any relationship between the presence of the prothrombin 20210A allele and either a family history of thromboembolism, the rate of recurrences or the age at disease onset. However, the co-inheritance in the same individual of both prothrombin 20210A allele and factor V Leiden was associated with a significantly lower age at disease onset suggesting a synergistic contribution of both abnormalities.

Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study.

OBJECTIVES: To assess the prevalence of activated protein C resistance (APC-R) among healthy subjects and thromboembolic patients and to determine the clinical characteristics associated with APC-R. DESIGN: A prospective study. SETTING: One academic medical centre. SUBJECTS: 91 health controls and 126 thromboembolic patients. MEASUREMENTS: Patients and control were genotyped for the factor V Leiden (VaQ506) mutation. The anticoagulant response of the patient's plasma to activated protein C was also determined. RESULTS: The frequency of APC-R was 3.3% among healthy control subjects and 22% among thrombotic patients of whom 18% were heterozygous and 4% were homozygous. The mean age at the first thrombotic event and the severity of thrombotic disease including the proportion of proximal deep vein thrombosis and the frequency of lung embolism were identical among APC-R positive and negative patients. A family history of thromboembolic disease was elicited more frequently in APC-R positive than in APC-R negative patients (57% vs. 22%, P < 0.001). The recurrence rate was higher for APCR-R positive patients (57% vs. 34%, P < 0.05). The percentage of cases with a factor predisposing to thrombosis was very similar in APC-R positive (57%) and negative (68%) patients. CONCLUSIONS: A familial history of thromboembolic disease and recurrences are significantly more frequent among APC-R positive than APC-R negative patients.

Recirculated normal platelets adhere to surfaces coated with plasma from patients with immune thrombocytopenia.

Immune thrombocytopenic purpura (ITP) patients have characteristic anti-platelet antibodies in their circulation. To assess the interaction between such antibodies adhering on to a non-physiological surface and human platelets, normal anticoagulated blood was perfused over ITP patient plasma-coated surfaces in a parallel plate flow chamber. At 300 s-1, platelet adhesion to patient plasma-coated glass coverslips (24.0 +/- 10%) was significantly higher than the adhesion to normal plasma-coated surfaces (9.8 +/- 7%). When perfused at 1300 s-1, the adhesion to patient plasma-(5.1 +/- 1.3%) and to normal plasma-(2.5 +/- 1.2%) coated coverslips were significantly weaker. Furthermore, patient platelet binding depended on simultaneous contributions by antibodies and fibrinogen present on the plasma-coated surface, since adherence was antagonized both by normal immunoglobulins added to the perfusate, as well as by the anti-GPIIb/IIIa monoclonal antibody 16N7C2, which competes with fibrinogen for binding to its receptor on the platelet. Accordingly, platelet adhesion was only observed to coverslips coated with the plasma but not the serum of ITP patients. Hence, perfusion of normal platelets over surfaces coated with ITP patient plasma enables a functional assessment of the presence in this plasma of anti-platelet antibodies.

Importance of a medical treatment in mesenteric vein thrombosis (MVT).

Mesenteric vein thrombosis (MVT) and particularly superior mesenteric vein thrombosis (SMVT) can induce 5 to 15 percent of mesenteric and intestinal infarctions in a small and large bowels. The thrombotic process can be idiopathic or consecutive to inherited or acquired thrombophilic states. The clinical diagnosis of this event remains difficult and requires always specific imaging investigation to treat as soon as possible. Its evolution and mortality rate are quite different than these observed in arterial mesenteric ischemic accident. Medical treatment with thrombolytic, anticoagulant, antiplatelet and antispasmodic agents, initiated promptly after precocious diagnosis is able not only to prevent surgical procedure but also to reduce significantly the mortality and recurrence rate of this venous thrombotic event.