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Background In ineffective erythropoiesis, hepcidin synthesis is suppressed by erythroid regulators, namely erythroferrone and growth differentiation factor-15. For the first time, the hypothesis that iron overload in megaloblastic anemia may be related to ineffective erythropoiesis is explored by describing the kinetics of hepcidin, erythroferrone, and growth differentiation factor-15 levels in a patient diagnosed with megaloblastic anemia associated with iron overload. Case presentation An 81-year-old Caucasian male was admitted for fatigue. He had type-2 diabetes previously treated with metformin, ischemic cardiac insufficiency, and stage-3 chronic kidney disease. Vitiligo was observed on both hands. Biological tests revealed normocytic non-regenerative anemia associated with hemolysis, thrombocytopenia, and elevated sideremia, ferritin, and transferrin saturation levels. Megaloblastic anemia was confirmed with undetectable blood vitamin B12 and typical cytological findings like hyper-segmented neutrophils in blood and megaloblasts in bone marrow. The patient received vitamin B12 supplementation. At 3 months, biological parameters reached normal values. Hepcidin kinetics from diagnosis to 3 months inversely correlated with those of erythroferrone and growth differentiation factor-15. Conclusions This case suggests that iron-overload mechanisms of dyserythropoietic anemias may apply to megaloblastic anemias.

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3–41.9) vs 63.9% (95% CI 5.1–72.7), p

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell&ndash, cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.

Clonal hematopoiesis (CH) of indeterminate potential has been described in blood samples from large series of patients. Its prevalence and consequences are still not well understood because sequencing methods vary and because most studies were performed in cohorts comprising individuals with nonhematologic diseases. Here, we investigated the frequency of CH in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers. Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. In bone marrow samples, clones were found in almost 40% of healthy volunteers more than 50 years old. The most frequent mutations were found in DNMT3A and TET2, with 1 individual carrying 3 variants. Variant allele frequencies were highly concordant between blood and bone marrow samples. Blood parameters were normal except for those in 2 individuals: 1 had a mild macrocytosis and 1 had a mild thrombocytosis. Furthermore, no morphologic abnormalities or dysplasia were detected when bone marrow smears were carefully evaluated. Individuals with CH differed from others by age (62.8 vs 38.6 years; P < .0001) and platelet count (294 vs 241 ×109/L; P = .0208), the latter being no more significant when removing the 2 individuals who carried the JAK2 p.V617F mutation. These results confirm that CH is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or the bone marrow.

Low reactive oxygen species (ROS) levels are well-established characteristics of mouse hematopoietic stem cells (HSCs). However, little is known about these levels in human HSCs. This study aimed at quantifying ROS levels in human CD34

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34posCD38low progenitor cells. Moreover, we identified a specific antioxidant signature, dubbed “antioxidogram,” for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with

The coexistence of dual hematological neoplasms is very rare. Sequential or synchronous neoplasms in hematology are an uncommon and complex clinical situation. The aim of the Hemo

Abernethy malformation is a rare congenital anomaly of the portal vein where the portal blood bypasses the liver. We report the first case of a patient with Abernethy malformation and tetralogy of Fallot associated with nodular regenerative hyperplasia and focal nodular hyperplasia (FNH), which finally evolved to a giant hepatocellular-cholangiocarcinoma (HCC-CC) of the liver, successfully resected. (Hepatology 2016;64:1800-1802).

Professionalism development entails learning to make judgments in ambiguous situations. A Concordance of Judgment Learning Tool (CJLT), comprised of 20 vignettes involving professionalism issues, was developed. Students obtained a measure of how concordant their judgments were with a panel of experts and learned from given explanations.Twenty clinical vignettes implying professionalism issues were written including, for each, four possible courses of action. Expert panel, nominated by all clerkship students, was made up of attending physicians that best represented professionalism role models. Experts completed CJLT and gave explanations for their answers. All clerks were invited to answer each vignette, and then received automated expert feedback including explanations.Seventy-nine students sat for the activity. The optimized test included 20 cases and 54 questions (Cronbach's alpha coefficient of 0.64). Student - expert concordance scores ranged from 54 to 77 with a mean at 64.6 (standard deviation 5.1). Satisfaction survey results indicated high satisfaction and relevance of tool despite some pitfalls. Post-test focus group data revealed relevant experiential learning on professionalism issues.Students' scores and perceptions suggest pedagogic relevance of the CJLT in fostering professionalism development in clerkship. CJLT is user-friendly and shows promise as a situation experiential learning activity.

of 50 physicians, postgraduate specialists, senior nurses, medical and nursing students and patients. Participants were asked to narrate critical incidents related to deficiencies in communication skills in physicians in which they had been involved or which they had witnessed first-hand. Eighty-one critical incident narrations were recorded and transcribed. They were analysed and grouped according to themes, categories and sub-categories. Communication skills deficiencies were identified from the themes, categories and sub-categories. In-depth analysis of communication gaps, cultural or contextual influences and their medical consequences were identified. One critical incident referred to the failure of a physician to identify the locus of decision making. An individual in need of surgery for a hernia was also at risk for cardiac complications during surgery. The patient felt that his family needed to make the decision, whereas the physician demanded that he make the decision. Another example referred to the fact that ward rounds are usually conducted in English, a language most patients do not understand. One day during discussions at the bedside, the word ‘surgery’ was mentioned causing much unnecessary anxiety and alarm in an elderly female patient. These are two of the incidents narrated which illustrate poor communication with medical consequences. What lessons were learned? Four categories of communication deficiency were developed from the narrated incidents: (i) content omission (8 sub-categories); (ii) inappropriate responses (6 sub-categories); (iii) inappropriate setting (4 sub-categories), and (iv) non-verbal communication issues (6 subcategories). These categories and sub-categories formed an interrelated framework for the content and learning activities of a new communication skills course for Sri Lankan doctors. Critical incident analysis themes provided the content necessary to design a culturally and contextually relevant solution to a significant problem in physician communication in Sri Lanka. The 81 authentic scenarios will also be useful in the teaching process during this course.