Recommendations for Pregnancy in Rare Inherited Anemias

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders

Cardiac Rehabilitation in Patients With Ventricular Assist Device

PURPOSE: The aim of this study was to investigate changes in exercise capacity (EC) and quality of life (QoL) of patients with ventricular assist devices (VADs) during cardiac rehabilitation (CR). METHODS: Data from patients with VAD implantation and subsequent CR between 2007 and 2017 were analyzed retrospectively. Measures of the 6-min walk test [6MWT] distance, Functional Independence Measure [FIM], ergometry, MacNew Heart Disease Questionnaire [MNH], and Hospital Anxiety and Depression Scale [HADS] at entry and discharge were examined. RESULTS: Data from 110 patients (age 53 ± 12 yr; male 82%) were analyzed. Patients improved during CR significantly in the 6MWT (114 ± 85 m, P < .001), ergometry (20 ± 17 W, P = .002), FIM (8 ± 7 points, P < .001), and MNH (0.8 ± 0.7 points, P < .001). Initial HADS levels were high with a mean value of 9 and did not improve during CR (-0.4 ± 5 points, P = .637). Significant differences of improvements in the 6MWT were observed between left and biventricular VAD (129 ± 90 m vs 85 ± 67 m, P = .043) as well as destination therapy and bridge-to-transplant (184 ± 88 m vs 102 ± 82 m, P = .005). CONCLUSIONS: Patients with VAD implantation had statistically and clinically significant improvements in EC and QoL as assessed with the MNH during CR. Patients on destination therapy showed a larger benefit from CR than bridge-to-transplant patients and patients with left VAD improved more than biventricular VAD patients

Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (151 74T and 151 034) and of SCF in 9 of 1 1 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS1 74T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of 151 74T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. 151 74T cells expressed the Mr 1 45,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of 151 74T by 40%. Interleukin 4 (11-4) completely inhibited SCF-induced proliferation of 151 74T cells. Interestingly, 11-4 induced an almost complete down-regulation of both c-kit and SCF expression in [Si 74T. Our findings suggest that in LS1 74T cells, an SCF-mediated autocrine loop is functional and that 11-4 down-regulates the expression of both the receptor and the ligand of this circuit