OPTIMAL MANAGEMENT OF CHRONIC HEART FAILURE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Chronic kidney disease and chronic heart failure are closely interlinked; an abnormality in one system adversely impacts upon the function of the other. Despite the wealth of evidence available for beneficial treatment strategies in chronic heart failure, the prognosis remains poor and optimum therapy under‐utilised. The applicability of proven therapies to patients with co‐morbidity remains a particular challenge, especially since marked renal impairment has often been an exclusion criteria in major studies. In this article we discuss the epidemiology and pathophysiology of the two conditions and then focus on the aspects of treatment most pertinent to those patients with heart failure patients and concomitant chronic kidney disease.     

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

Objective: Iron isomaltoside (Monofer^®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA.

Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000?mg of iron isomaltoside infused in single doses up to 2000?mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters.

Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500?mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0?g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found.

Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000?mg and cumulative doses up to 3000?mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.     

Anémie chez les patients avec syndrome coronarien aigu au centre hospitalier de Vichy

IntroductionObjectives were to determine the clinical, epidemiological and biological profile of the patients suffering from acute coronary syndrome and presenting the anaemia, the determinants of variation of the haemoglobin rate, and to estimate the impact of the anaemia on the prognosis of these patients.Patients and methodsRetrospective and observational study conducted in the cardiology department of Vichy Hospital in France. All patients with acute coronary syndrome admitted from 31 of October 2015 to 30 of April 2016 were selected. The patients were followed for 1 month. The anaemia was defined by: less than 13 g/dL in man and less than 12 g/L in woman (WHO definition). Biological markers were taken at the admission. Factors associated to the haemoglobin rate were analysed by multivariate linear regression and those associated to the mortality within 30 days were analysed by logistic regression.ResultsAmong 251 included patients, there were 180 males and 71 females with the average age of 67 years. 94 patients had ST elevation myocardial infarction (STEMI), 116 had Non ST myocardial infarction (NSTEMI) and 41 had unstable angina. Haemoglobin value was known in 238 patient's, among whom 44.1% were anaemic (105/238). The anaemia was more frequent in women. The tobacco was less frequent; High blood pressure, renal failure, malnutrition, subclinical atherosclerosis, lower limb arteritis and the inflammatory syndrome were more frequent in patients with anaemia. They presented more complications. The age (P = 0,003), the pulsed pressure (P = 0,007), LVEF (P = 0,005), the albumin (P = 0,010), Creatine kinase (CK) level (P = 0,048) and of CRP (P = 0,011), were linear factors of variations of the haemoglobin rate (R² = 0,955). Ten patients died during the follow-up. The multivariate analysis revealed the anaemia as independently associated with the mortality in 30 days (Odds Ratio 3,69; P = 0,02).ConclusionAnaemia is frequent in patients with an ACS, and it is associated with a particular clinical and biological profile. The patients with anaemia have a mortality rate in 30 days higher than the patients without anaemia.     

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

Growing awareness that heart failure, renal impairment, and anaemia are frequent co‐morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR‐HF trial raises a new hypothesis: is it time for ‘CRAS’ to be supplemented with new acronyms such as CRIDS (cardiorenal–iron deficiency syndrome) or even CRAIDS (cardiorenal–anaemia–iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14–2.17, P = 0.005). In the FAIR‐HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron‐deficient patients with heart failure, even in non‐anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.     

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.     

Treatment of anaemia in inflammatory bowel disease with iron sucrose

Background: Inflammatory bowel disease (IBD)‐associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. Methods: Sixty‐one patients with IBD and anaemia (average haemoglobin 97?g/L) were treated with iron sucrose (iron dose 1.4?±?0.5?g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of ≥20?g/L or to normal haemoglobin levels (≥120?g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. Results: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty‐four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow‐up period of 117?±?85 (4–291) (mean?±?s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. Conclusions: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow‐up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.     

Erythroblast Iron Metabolism in Sideroblastic and Sideropenic States

Iron appears to exert self-regulatory control over erythroblast iron uptake, iron storage and its incorporation into haem. It does this via iron regulatory proteins (IRPs) which bind reversibly to the iron responsive elements (IREs) on the mRNA of transferrin receptor (TfR), erythroid 5-aminolaevulinic acid synthase (ALA-S2) and ferritin. Iron deficiency leads to the binding of IRP to IRE. This binding inhibits the translation of mRNA for ALA-S2 and ferritin but stabilizes mRNA for TfR expression.

Sideroblastic erythropoiesis is highly ineffective and characterized by mitochondrial iron loading. The study of X-linked sideroblastic anaemia has shown that the entry of iron into the mitochondria is poorly controlled and able to occur when protoporphyrin production is reduced, as is seen with the ALA-S2 mutations, or when it is increased as has been seen with ABC7 transporter mutations.

Sideropenia characterises both iron deficiency anaemia (IDA) and the anaemia of chronic disease (ACD). Erythroblasts in ACD seem doubly equipped to protect their iron supply with their ability to increase the efficiency of transferrin-iron uptake as well as to activate the IRP/IRE system to increase surface TfR production. This increase in efficiency restricts the need to increase surface TfR production and maintains serum soluble TfR (sTfR) values within the normal range in iron replete ACD. The coexistence of iron deficiency with chronic disease, however, is associated with an increase in both the efficiency and number and a highly significant rise in sTfR values.     

The role of the bone marrow in bovine trypanotolerance I. Changes in blood and bone marrow inTrypanosoma congolense-infected cattle

This study compared the changes in the bone marrow (BM) of five trypanotolerant N'Dama cattle with those of four trypanosusceptible Boran cattle during trypanosome infection. In the early parasitaemic phase, from 12 to 21 days postinfection (DPI), tsetsetransmitted primaryTrypanosoma congolense IL 1180 infection induced parasitaemia, slight depression in packed cell volume (PCV), marked leucopenia due to lymphocytopenia and eosinopenia, and thrombocytopenia which were of similar intensity in Boran and N'Dama cattle. However, from 28 DPI until the end of the experiment on 112 DPI, the parasitaemia was higher in the Boran than in the N'Dama. Severe anaemia and leucopenia characterised by lymphopenia, neutropenia, eosinopenia and monocytopenia persisted in Boran cattle. In contrast, the PCV values dropped gradually in N'Dama cattle and from 77 DPI recovered slowly to values just below preinfection levels by 112 DPI. The total and differential leucocyte counts of the N'Dama cattle stabilised at approximately two-thirds of preinfection values between 28 and 112 DPI, and were double those of the Boran. Marked thrombocytopenia occurred in both breeds. The anaemia was initially macrocytic hypochromic but terminally became microcytic hypochromic in both breeds. Light and electron microscopic studies of sequential biopsies of the BM of these animals showed that the BM response was the key to these differences between the N'Dama and Boran. The biopsies of the BM of the N'Dama cattle were hypercellular (scored 4.5±1.0 compared to 4.0 for controls) with mild hyperplasia of erythroid cells and mild hypoplasia of myeloid cells from 28 to 112 DPI, endowing the animals with higher haemopoietic potential that enabled them to replace most lost cells. In contrast, the Boran cattle had hypocellular (scored 2.4±1.1) BM biopsies with relative erythroid hyperplasia and myeloid hypoplasia, resulting in low capacity of cell replacement manifested as severe unremitting anaemia and leucopenia. The BM of both breeds showed moderate hyperplasia of cells of the mononuclear phagocyte system. Therefore, this study showed, for the first time, that BM response is a key determinant factor of trypanotolerance as it determines the animal's capability for blood cell regeneration.     

三种采集血标本方法的效果比较

目的：探讨三种体位对采集血标本效果的影响。方法：对我院门诊177例需要输血和血标本采集的地中海贫血患儿或血液病患儿，根据穿刺肢体下垂角度的不同随机分为三组：以心脏为水平线，穿刺肢体下垂45°角为实验1组；肢体下垂90°角为实验2组；常规体位为对照组（穿刺部位与心脏同一水平位）。将三种方法的血标本合格数、穿刺成功率、操作时间、血管保护、患者满意率等指标进行统计分析。结果：穿刺肢体下垂45°角与对照组有显著性差异。结论：穿刺肢体下垂45°角体位进行血标本采集，方便操作，成功率高，减轻患儿痛苦，提高患者满意率，有效保护血管，是血标本采集的最佳体位，尤其适用于地中海贫血患儿的输血治疗。