Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

Epithelial Progenitors in the Normal Human Mammary Gland

The human mammary gland is organized developmentally as a hierarchy of progenitor cells that become progressively restricted in their proliferative abilities and lineage options. Three types of human mammary epithelial cell progenitors are now identified. The first is thought to be a luminal-restricted progenitor; in vitro under conditions that support both luminal and myoepithelial cell differentiation, this cell produces clones of differentiating daughter cells that are exclusively positive for markers characteristic of luminal cells produced in vivo (i.e., keratins 8/18 and 19, epithelial cell adhesion molecule [EpCAM] and MUC1). The second type is a bipotent progenitor. It is identified by its ability to produce mixed colonies in single cell assays. These colonies contain a central core of cells expressing luminal markers surrounded by cells with a morphology and markers (e.g., keratin 14⁺) characteristic of myoepithelial cells. Serial passage in vitro of an enriched population of bipotent progenitors promotes the expansion of a third type of progenitor that is thought to be myoepithelial-restricted because it only produces cells with myoepithelial features. Luminal-restricted and bipotent progenitors can prospectively be isolated as distinct subpopulations from freshly dissociated suspensions of normal human mammary cells. Both are distinguished from many other cell types in mammary tissue by their expression of EpCAM and CD49f (6 integrin). They are distinguished from each other by their differential expression of MUC1, which is expressed at much higher levels on the luminal progenitors. To relate the role of these progenitors to the generation of the three-dimensional tubuloalveolar structure of the mammary tree produced in vivo, we propose a model in which the commitment to the luminal versus the myoepithelial lineage may play a determining role in the generation of alveoli and ducts.     

La reconstruction des enveloppes psychiques et environnementales dans les dessins d’enfants des rues en Haïti : une étude post-séisme

Objectives

The objective of this paper is to show how children and adolescents, living in the street in Haïti after the 2010 earthquake, use the street as a space to rebuild their identity. Using drawings of children and adolescents encountered in the context of research on resilience and the creative process among child and adolescent victims of the earthquake (ANR-10-HAIT-002 RECREAHVI), we explored the difficulties, the trauma and the creative expression of these children in the aftermath of the earthquake. These young people found themselves in a particularly vulnerable situation, whether socially, psychologically, or in terms of their safety. Their environmental envelopes were uncertain, fluctuating or damaged, so that the psychic envelopes of these street children was also put to the test. This article concerns the analysis of the drawings of street children and adolescents. We focus on the characteristics of the graphic envelopes to understand how these young street-dwellers symbolize the damage to their environmental and psychic envelopes, and how they express their needs for reconstruction.

Does Primary Surgical Management of Liver Hydatid Cyst Influence Recurrence?

Background and aims  

Hydatid disease is still a major health problem in sheep-raising areas. Surgery remains the basic treatment for liver hydatid cyst (LHC). However, recurrences can occur after all therapies. Surgery for recurrence of LHC becomes technically more difficult with higher rate of morbidity and mortality. The aim of this study was to determine perfective factors associated to hepatic recurrence after LHC surgery and to propose and discuss postoperative follow-up schedules.     

Relevant factors in mitral valve reconstructive surgery. Report of 150 cases

150 patients had mitral valve repair for mitral valve incompetence. There were 57 males and 93 females with a mean age of 22 years, 39% were less than 15 years of age. 60% of the patients were in Class II NYHA and 40% in Class III and IV. According to Carpentier's classification, isolated type I was present in 18 patients (12%), type II in 98 patients (64%) and type III in 34 cases (24%). Mitral repair included correction of valve prolapse, valvular enlargement with pericardial patch and annuloplasty with semi-rigid ring in 128 cases and PTFE patch along the posterior leaflet in 12 cases. The perioperative mortality rate was 2.6% (4 patients). All patients had early post-operative echocardiography. According to this, mitral regurgitation was absent or tiny in 135 patients (92%), grade II in 10 cases and grade III in 2 cases. It was moderate or important in twelve patients (8%). In the late post-operative period, three patients were lost to follow-up. All the others patients were reoperated upon for mitral dysfunction in a mean time of 37 months. The reason for reoperation was in the majority of the cases the recurrence of mitral regurgitation related to increase of valvular and sub valvular disease. The late mortality rate is 7% (10 patients). Out of 126 reviewed survivors on the long run, 71 patients (56%) are asymptomatic in class I, 53 patients (42%) in class II and 2 patients in class III NYHA. Mitral valvuloplasty is the preferred procedure in mitral insufficiency surgical management. It is associated to a low early mortality and morbidity rate. Despite the need for reoperation in about 10% of the cases in the long follow-up, mitral repair offers a good quality of life without anticoagulant treatment.     

Semisynthesis of new sarcophine derivatives with chemopreventive activity

The natural cembranolide sarcophine (3) and its lactone ring-opened analogue (10) were oxidized using selenium dioxide under different reaction temperatures to prepare hydroxylated derivatives. Nine new compounds were obtained, six of them targeted hydroxylated derivatives. The determination of regio- and stereochemistry as well as the mechanistic considerations on the selectivity observed in these reactions are discussed on the basis of 2D NMR and molecular modeling. In preliminary in vitro tests on inhibition of EBV-EA activation, compounds 10 and 12-15 have shown higher activity than the known chemopreventive agent sarcophytol A.     

Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction

Studies during the past decade have provided a better understanding of the potential mechanisms responsible for the pathogenesis of preeclampsia. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion as a result of abnormal cytotrophoblast invasion of spiral arterioles. Placental ischemia/hypoxia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium which results in enhanced formation of endothelin, thromboxane, and superoxide, increased vascular sensitivity to angiotensin II, and decreased formation of vasodilators such as nitric oxide and prostacyclin. These endothelial abnormalities, in turn, cause hypertension by impairing renal function and increasing total peripheral resistance. While recent studies support a role for cytokines and other factors such as lipid peroxides and reactive oxygen intermediates as potential mediators of endothelial dysfunction, finding the link between placental ischemia/hypoxia and maternal endothelial and vascular abnormalities remains an important area of investigation. The quantitative importance of the various endothelial and humoral factors in mediating the vasoconstriction and elevation in arterial pressure during preeclampsia has also not been completely elucidated.     

Alpha interferon in children with Philadelphia chromosome-positive chronic myeloid-leukaemia

The present work focuses on the therapeutic efficacy and the toxicity of alpha interferon in patients younger than age 18 years. 5 patients younger than 18 years were treated and followed up between 1990 and 1999 at the department of haematology (Aziza Othmana Hospital) Hydroxyurea was given as initial treatment to all patients. After a median period of 8 months, these patients received alpha interferon (5 millions units/m2 once). Six months after the beginning of the alpha interferon a complete hematologic response was obtained in all patients. The median overall survival was of 66 months: 3 patients are still alive (2 patients in an advanced stage and one patient in chronic phase) and 2 patients died after transformation. The most common reported side effects of alpha interferon were asthenia, weight loss, fever, myalgia, chills and headaches--these toxic manifestations were mild and were noticed in all our patients. Myelosuppression was noted in two patients. Interferon is well tolerated in patients younger than age years 18 old, with CML. It may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without histocompatible donor. The role of new agents such as STI 571 needs to be evaluated as well.