Background Transcatheter mitral valve in ring procedure has emerged as a minimally invasive alternative to re-do surgery among patients with failed mitral annuloplasty rings. Uncommonly, haemolysis ...presents as a complication after the percutaneous valvular procedures and often require aggressive measures to correct paravalvular leaks and mechanical collision. Case summary We report a case of an 82-year-old female who underwent a transcatheter valve in ring procedure (Edwards Sapien S3, Edwards Lifesciences) for symptomatic severe mitral regurgitation from a bioprosthetic annuloplasty ring failure complicated by acute haemolytic anaemia a week after the procedure manifesting as dark coloured urine, profound icterus, and acute renal injury. She was treated with a post-dilation balloon valvuloplasty leading to reduction in haemolysis, but the patient was readmitted with acute haemolysis episode again. At this time, a decision was made to perform a repeat valve in valve TMVR with a 29 mm S3 Edwards Sapien valve which led to a resolution of haemolysis. Discussion In this case, the leaflets of previously placed S3 valve sealed the blood flow through the valve frame thus diverting the blood flow away from the area of collision leading to resolution of haemolysis. Keywords Haemolytic anaemia * Transcatheter mitral valve in ring * Mitral valve disease * Haemolysis * Case report ESC curriculum 4.3 Mitral regurgitation * 7.4 Percutaneous cardiovascular post-procedure
A detailed description of equine infectious anemia virus and host responses to it are presented. Current control and eradication of the infection are discussed with suggestions for improvements to ...increase their effectiveness.
Summary Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially ...reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ0 thalassaemia, were aged 9–18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on99 Tc spleen scan) and renal function (glomerular filtration rate by99m Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2–4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00006400. Findings 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m2 , p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. Interpretation On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. Funding The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.
Disease Overview
Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory ...anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS‐RS) and RARS with thrombocytosis (RARS‐T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN‐RS‐T).
Diagnosis
MDS‐RS is a lower‐risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥ 15% BM RS (≥5% in the presence of SF3B1 mutations). MDS/MPN‐RS‐T, now a formal entity in the MDS/MPN overlap syndromes, has diagnostic features of MDS‐RS‐SLD, along with a platelet count ≥450 × 10(9)/L and large atypical megakaryocytes.
Mutations and Karyotype
Mutations in SF3B1 are seen in ≥80% of patients with MDS‐RS‐SLD and MDS/MPN‐RS‐T, and strongly correlate with the presence of BM RS; MDS/MPN‐RS‐T patients also demonstrate JAK2V617F, ASXL1, DNMT3A, SETBP1, and TET2 mutations. Cytogenetic abnormalities are uncommon in both.
Risk stratification
Most patients with MDS‐RS‐SLD are stratified into lower‐risk groups by the revised‐IPSS. Disease outcome in MDS/MPN‐RS‐T is better than that of MDS‐RS‐SLD, but worse than that of essential thrombocythemia. Both diseases have a low risk of leukemic transformation.
Treatment
Anemia and iron overload are complications seen in both and are managed similar to lower‐risk MDS and MPN. The advent of luspatercept, a first‐in‐class erythroid maturation agent will tremendously boost the ability to manage anemia. Aspirin therapy is reasonable in MDS/MPN‐RS‐T, especially in the presence of JAK2V617F, but the value of platelet‐lowering drugs remains uncertain.
Summary
Iron deficiency and anaemia are global health problems and major causes of morbidity in women. Current definitions of anaemia in women are historic and have been challenged by recent data ...from observational studies. Menstrual loss, abnormal uterine bleeding and pregnancy put women at risk of developing iron deficiency which can result in severe fatigue, reduced exercise capacity and poor work performance. Iron deficiency and anaemia during pregnancy are associated with adverse maternal and fetal outcomes, including neurocognitive deficits in children born to iron‐deficient mothers. Both iron deficiency and anaemia are common in women undergoing surgery but their association with poor outcomes remains uncertain. The enduring burden of iron deficiency and anaemia in women suggests that current strategies for recognition, prevention and treatment are limited in their utility. Improvements in our understanding of iron homeostasis and the development of new iron preparations, which are better absorbed with fewer side‐effects, may improve therapeutic effectiveness of oral iron. Intravenous iron is efficacious for correcting anaemia rapidly but high‐quality data on patient‐centred outcomes and cost‐effectiveness are currently lacking. Many recommendations for the treatment of iron deficiency and anaemia in national guidelines are not supported by high‐quality evidence. There is a need for robust epidemiological data and well‐designed clinical trials. The latter will require collaborative working between researchers and patients to design studies in ways that incorporate patients’ perspectives on the research process and target outcomes that matter to them.
Fanconi anaemia (FA) is a cancer predisposition syndrome characterized by cellular sensitivity to DNA interstrand crosslinkers. The molecular defect in FA is an impaired DNA repair pathway. The ...critical event in activating this pathway is monoubiquitination of FANCD2. In vivo, a multisubunit FA core complex catalyzes this step, but its mechanism is unclear. Here, we report purification of a native avian FA core complex and biochemical reconstitution of FANCD2 monoubiquitination. This demonstrates that the catalytic FANCL E3 ligase subunit must be embedded within the complex for maximal activity and site specificity. We genetically and biochemically define a minimal subcomplex comprising just three proteins (FANCB, FANCL, and FAAP100) that functions as the monoubiquitination module. Residual FANCD2 monoubiquitination activity is retained in cells defective for other FA core complex subunits. This work describes the in vitro reconstitution and characterization of this multisubunit monoubiquitin E3 ligase, providing key insight into the conserved FA DNA repair pathway.
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•A native Fanconi anaemia core complex is purified from vertebrate cells•Purified FA core complex monoubiquitinates FANCD2 in vitro•FANCB, FANCL, and FAAP100 constitute the minimal monoubiquitination module•Other subunits contribute to maximal activity and site specificity of FANCL
FANCD2 monoubiquitination by the multisubunit Fanconi anaemia (FA) core complex is the key activating event in a conserved DNA repair pathway. Rajendra et al. now purify the core complex and reconstitute the monoubiquitination event in vitro. Genetic and biochemical dissection define a three-component subcomplex that functions as the catalytic monoubiquitination module.
Aplastic Anemia Young, Neal S
The New England journal of medicine,
10/2018, Letnik:
379, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Once a uniformly fatal disease, aplastic anemia is now curable with allogeneic transplantation in 80% of children and 40% of adults, and immunosuppression with or without eltrombopag can induce long ...remissions in most adults.
Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple ...clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).
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