Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.     

Natural history and risk factors of long-term mortality in acute coronary syndrome patients with cardiogenic shock

PurposeCardiogenic shock (CS) is a severe complication of acute coronary syndromes (ACS). Intra-aortic balloon pump (IABP) is considered important mechanical therapy for acute CS. We aimed to analyze the natural history and possible prognostic factors in patients with CS complicating ACS.Patients/methodsAll 126 patients (mean age 65.8 ± 12.5 years), who were hospitalized in single center due to an episode of CS in the course of ACS, had IABP and were scheduled for coronary angiography. The assessed end-point was 5-year death from any cause.ResultsMedian left ventricle ejection fraction (LVEF) 28% (interquartile range (IQR) 23–35%), 39 patients (31%) were female, in 91 (72%) the initial diagnosis was ST-elevation myocardial infarction (STEMI). Mean time on the IABP was 3.8 ± 3 days. During index hospitalization there were 56 deaths (44%). Other 27 patients (out of 70 discharged – 38.5%) died during 5-year follow-up. In univariate logistic regression, the significant effect on long term mortality had age, female gender, reduced ejection fraction below 31% and hypotension on admission. The out of hospital survival was also determined by age, gender and hypotension, while LVEF lost its predictive value The multivariate survival analysis both in whole group and in patients discharged from hospital was independently affected by age and hypotension on the admission.ConclusionsThe mortality of patients with CS despite treatment with IABP remains very high, especially during the in-hospital period and early after discharge. Among assessed parameters age and hypotension on the admission are the most important predictors of adverse long term prognosis.     

Labile plasma iron,more practical and more sensitive to iron overload in myelodysplastic syndromes

Objectives: In order to gain an insight into labile plasma iron (LPI) in iron metabolism microenvironment in MDS.

Methods: We performed ELISA, quantitative real-time polymerase chain reaction, flow cytometry, MRI T2* assays to test LPI, iron biochemical parameters, and liver iron concentration (LIC) among 22 MDS patients.

Results: LPI has a statistical difference (P?P?=?0.086 by ANOVA). After DFO treatment, serum hepcidin expression increased from 301.26?±?59.78 to 340.33?±?49.78?µg/l (P?=?0.032), while hepcidin/ASF was upregulated gradually from 0.16?±?0.08 to 0.22?±?0.03 (P?=?0.045). APAF-1 expression (P?=?0.047) and erythroid apoptosis rate (P?=?0.009) decreased significantly, respectively. No statistical difference was found in EPO (P?=?0.247) and GDF15 expression (P?=?0.172). LIC dropped from 9.83?±?4.84 to 6.28?±?4.01?mg/g dry weight (P?P?=?0.594). LPI has a closer connection to LIC than ASF (r?=?0.739, P?r?=?0.321, P?=?0.034).

Discussion: LPI seems to be a real-time indicator which reflects body iron loading status instantaneously. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens.     

Distinguishing constitutional from acquired bone marrow failure in the hematology clinic

Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune aplastic anemia, the commonest BMF, is a diagnosis of exclusion. In this review, we discuss a general approach to the evaluation of BMF, focusing on clinical presentations particular to immune and various constitutional disorders as well as the interpretation of bone marrow histology, flow cytometry, and karyotyping. Additionally, we examine the role of specialized testing in both immune and inherited BMF, and discuss genetic testing, both its role in patient evaluation and interpretation of results.     

Acute coronary syndromes with ongoing myocardial ischemia (ACS with OMI) versus acute coronary syndromes without ongoing ischemia (ACS without OMI): The new classification of acute coronary syndromes should replace old classification based on ST segment elevation presence or absence—Expert consensus statement of the Czech Society of Cardiology

The Czech Society of Cardiology is proposing here the new classification of acute coronary syndromes at the time of the first medical contact. The proposal suggests to remove the terms “ST elevation myocardial infarction” and “non-ST elevation acute coronary syndrome” and to replace these terms by “acute coronary syndrome with ongoing myocardial ischemia” and “acute coronary syndrome without ongoing myocardial ischemia”. The proposed new classification better reflects current treatment approaches and will facilitate the decision making at the first medical contact.     

Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A₂ synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.     

New drugs for the treatment of coronary artery syndromes: otamixaban and ticagrelor

Acute coronary syndromes are a major cause of mortality and morbidity. The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anticoagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the antiplatelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.