Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long-term survivors after allogeneic hematopoietic stem cell transplantation

We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 μg/L. Liver iron content (LIC) was 117 μmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (

Exploiting Mitochondrial Dysfunction for Effective Elimination of Imatinib-Resistant Leukemic Cells

Challenges today concern chronic myeloid leukemia (CML) patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention

Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity. In the present study, we show that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) protected from cisplatin-induced nephrotoxicity and neuropathic pain in mice with or without tumors. Moreover, we also demonstrate that the antitumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and could even be potentiated. Altogether, our results support the use of istradefylline as a valuable preventive approach for the clinical management of patients undergoing cisplatin treatment

Leucocytosis-induced plasma hyperkalaemia in samples conveyed by a pneumatic transport system: tips and tricks

[no abstract available

Potential of the Sebia Capillarys® neonat fast automated system for neonatal screening of sickle cell disease

Peer Reviewe

Leukocytosis interference in clinical chemistry: shall we still interpret test results without hematological data?

Background: Extreme leukocytosis is known to induce remarkable variations of some clinical chemistry tests, thus leading to possible clinical misinterpretation. This study aimed to define whether also moderate leukocytosis may influence the stability of glucose and blood gases. Methods: Blood samples are sent to the local laboratory through a pneumatic tube system. Clinical chemistry testing is routinely performed using Lithium-heparin tubes (for glucose) and heparin blood gases syringes (for blood gas analysis). Stability of glucose (in uncentrifuged blood tubes) and blood gases (in syringes) was hence evaluated in samples maintained at room temperature. Results were also analyzed in 2 subgroups of samples with different leukocyte counts, i.e., those with leukocytes <15 7 109/L and those with leukocytes >15 7 109/L. Results: An accelerated decrease of pH was observed in blood gases syringes with leukocytosis (i.e., >15 7 109/L), while no difference was noted for other blood gases parameters (PCO2, PO2). Spurious and time-dependent hypoglycemia was noted in uncentrifuged blood tubes of patients with leukocytosis. Conclusions: The results of our study suggest that even modest leukocytosis (i.e., around 15 7 109/L), which is frequently encountered in clinical and laboratory practice, may be associated with significant variations of both glucose and pH. This would lead us to conclude that results of these parameters shall be accompanied by those of hematologic testing to prevent clinical misinterpretation, namely with leukocyte counts

Pneumatic tube system transport and false hyperkalemia related to leukocytosis: a retrospective analysis

Extreme leukocytosis may lead to false hyperkalemia when blood samples are conveyed by pneumatic tube system (PTS). The aim of this study was to define whether even moderate leukocytosis and also non malignancy cells like neutrophils may influence potassium values after PTS transportation. Materials and methods. Uncentrifuged blood samples are sent to the local laboratory through PTS. Data were retrospectively collected from routine testing carried out on all specimens arrived in the laboratory between September 2017 and March 2018. Clinical chemistry testing is routinely performed using lithium-heparin tubes. When false hyperkalemia induced by leukocytosis is suspected, potassium measurement is then performed in serum (clotting activator tubes) or whole blood samples. The analysis was focused on samples with both leukocytosis (i.e., >15 x 10(9)/L) and plasma potassium >5.0 mmol/L, before any corrective therapeutic measure to lower potassium levels was established. Results. A total number of 18 samples were included in our analysis, 9 drawn from patients with hematologic malignancies and 9 without. In the 9 patients without hematologic malignancies (median leukocyte count, 20.4 x 10(9)/L), the median potassium value was 5.4 mmol/L in plasma and 4.5 mmol/L in serum or whole blood. In the 9 patients with hematologic malignancies (median leukocyte count, 151.9 x 10(9)/L; p <0.001), the median potassium value was 7.7 mmol/L in plasma and 4.3 mmol/L in serum or whole blood (median difference, 2.9 mmol/L; p <0.001). Conclusion. The results of our study suggest that even modest leukocytosis (i.e., around 15x10(9)/L), which can be frequently encountered in clinical practice, may be associated with a significant variation of plasma potassium. This would lead us to conclude that plasma samples transportation by PTS should be avoided in patients with even mild leukocytosis

Albumin-adjusted calcium and ionized calcium for assessing calcium status in hospitalized patients

Albumin-Adjusted Calcium and Ionized Calcium for Assessing Calcium Status in Hospitalized Patients

Addition of regular insulin to ternary parenteral nutrition: a stability study

International audienceBACKGROUND: Parenteral nutrition (PN) is a complex medium in which added insulin can become unstable. The aim of this study is, therefore, to evaluate the stability of insulin in PN and to identify influencing factors.METHODS: A total of 20 IU/L of regular insulin was added to PN in either glass or Ethylene Vinyl Acetate (EVA) containers. A 24 h stability study was performed via an electrochemiluminescence immunoassay in different media: A ternary PN admixture, separate compartments of the PN bag and a binary admixture. This study was repeated in the absence of zinc, with the addition of serum albumin or tween and with pH adjustment (3.6 or 6.3). Insulin concentration at t time was expressed as a percentage of the initial insulin concentration. Analysis of covariance (ANCOVA) was applied to determine the factors that influence insulin stability.RESULTS: In all PN admixtures, the insulin concentration ratio decreased, stabilising at a 60% and then plateauing after 6 h. At pH 3.6, the ratio was above 90%, while at pH 6.3 it decreased, except in the amino acid solution. ANCOVA (r2pCONCLUSIONS: A low pH level seems to stabilise insulin in PN admixtures. The influence of dextrose content suggests that insulin glycation may influence stability

Accuracy of alpha amylase in diagnosing microaspiration in intubated critically-ill patients.

Amylase concentration in respiratory secretions was reported to be a potentially useful marker for aspiration and pneumonia. The aim of this study was to determine accuracy of α-amylase in diagnosing microaspiration in critically ill patients.Retrospective analysis of prospectively collected data collected in a medical ICU. All patients requiring mechanical ventilation for at least 48 h, and included in a previous randomized controlled trial were eligible for this study, provided that at least one tracheal aspirate was available for α-amylase measurement. As part of the initial trial, pepsin was quantitatively measured in all tracheal aspirates during a 48-h period. All tracheal aspirates were frozen, allowing subsequent measurement of α-amylase for the purpose of the current study. Microaspiration was defined as the presence of at least one positive tracheal aspirate for pepsin (>200 ng.mL-1). Abundant microaspiration was defined as the presence of pepsin at significant level in >74% of tracheal aspirates.Amylase was measured in 1055 tracheal aspirates, collected from 109 patients. Using mean α-amylase level per patient, accuracy of α-amylase in diagnosing microaspiration was moderate (area under the receiver operator curve 0.72±0.05 [95%CI 0.61-0.83], for an α-amylase value of 1685 UI.L-1). However, when α-amylase levels, coming from all samples, were taken into account, area under the receiver operator curve was 0.56±0.05 [0.53-0.60]. Mean α-amylase level, and percentage of tracheal aspirates positive for α-amylase were significantly higher in patients with microaspiration, and in patients with abundant microaspiration compared with those with no microaspiration; and similar in patients with microaspiration compared with those with abundant microaspiration. α-amylase and pepsin were significantly correlated (r2 = 0.305, p = 0.001).Accuracy of mean α-amylase in diagnosing microaspiration is moderate. Further, when all α-amylase levels were taken into account, α-amylase was inaccurate in diagnosing microaspiration, compared with pepsin