Glomerular hyperfiltration and albuminuria are two pathological conditions that could alter renal drug elimination, but they have been rarely studied in a critical care setting. The aims of this descriptive, prospective study performed on 89 critically ill patients are to determine rates of glomerular hyperfiltration (main objective) and albuminuria (secondary objective). On admission, 17.9% of patients presented with glomerular hyperfiltration, climbing to rates as high as 30% during the first week of admission. Seventy-five percent showed albuminuria on admission, with rates remaining high throughout the week of the study. Since glomerular hyperfiltration as well as albuminuria are frequent pathophysiological conditions in critical care patients, the implications that these phenomena may have regarding drug elimination need further evaluation.

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Chromosomal translocations in hematological malignancies often result in novel fusion chimeric genes. We report a case of acute myeloid leukemia with a clonal translocation t(11;12)(p15;q13) display- IntroductionChromosomal translocations in hematological malignancies often result in the generation of novel chimeric genes. The nucleoporin 98 gene (NUP98) located at chromosome 11p15 is recurrently involved in a variety of rearrangements in both myeloid and lymphoid malignancies. 1,2 After the first NUP98 rearrangement, Homeobox A9 gene (NUP98/HOXA9), was discovered, more than 20 different fusion partners were reported. 1 Among these partners, other homeobox and non-homeobox genes have been identified as fusion partners of NUP98. We report here a novel NUP98 rearrangement in a patient with acute myeloid leukemia displaying morphologic and immunophenotypic features resembling the classical hypergranular subtype of acute promyelocytic leukemia. This case harbored a novel fusion gene as a result of a chromosomal break point at 12q13 detected in a new 11p15 rearrangement. The gene fused to NUP98 was identified by comparative genomic hybridization (CGH) array as the retinoid acid receptor gamma gene (RARG). RARG is a member of the nuclear receptor superfamily and shares high homology (90%) with RARA and RARB, the other retinoic acid receptors that are involved in retinoid signaling. While an artificial construct has been reported in which RARG is fused to the promyelocytic leukemia gene product (PML), resulting in an oncogenic protein, 3 no cases of human leukemia-bearing RARG fusions have been described. Methods Case reportsThis study was approved by the institutional review board of the Hospital Universitario La Fe. A 35-year-old man was referred to our department with asthenia, mucosal bleeding, spontaneous ecchymoses, and fever. Blood tests showed a hemoglobin level of 6 g/dL, a platelet count of 8 ϫ 10 9 /L, and a white blood cell count of 12 ϫ 10 9 /L with 82% blasts and atypical promyelocytes. Although increased levels of D-dimer were present, the patient did not fulfill the criteria for coagulopathy. 4 Morphologic examination of bone marrow (BM) smears disclosed a monomorphic infiltration by blast cells, 80% hypergranular (atypical promyelocytes, which frequently displayed Auer rods) resembling the hypergranular subtype of acute promyelocytic leukemia (M3) of the French-American-British classification ( Figure 1A-B). The immunophenotype of peripheral blood blasts was positive for CD13, CD33, CD45, CD117, and cMPO, weakly positive for CD34, and negative for HLA-DR and B-cell and T-cell markers. The immunofluorescence staining with the anti-PML monoclonal antibody (PG-M3) 5 was negative in both BM and peripheral blood samples. Moreover, reverse transcription polymerase chain reaction (RT-PCR) to amplify the PML/RARA fusion gene and conventional karyotyping to search for the t(15;17) were also negative. Due to the clinical suspicion of acute promyelocytic leukemia, the patient was started on all-trans retinoic ac...

BackgroundFms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and MethodsWe evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis. ConclusionsFLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens. monochemotherapy. Haematologica 2011;96(10):1470-1477. doi:10.3324/haematol.2011 This is an open-access paper.

Red blood cell distribution width (RDW) is a routine red blood cell count parameter which has been shown to be associated with inflammatory parameters. Recently, some authors proposed that RDW seems to be a marker of an adverse lipidic profile. In order to clarify whether RDW is related to inflammation, plasma lipids, or both, we determined anthropometric, hematimetric, inflammatory and lipidic parameters in 1111 healthy subjects. RDW correlated directly with age, body mass index (BMI), inflammatory parameters (plasma viscosity, erythrocyte sedimentation rate (ESR), fibrinogen, leukocyte and neutrophil count), and inversely with iron and hematimetric parameters (P < 0.05). When subjects were divided according to gender, RDW correlated inversely with triglycerides only in women (P < 0.05). When subjects were classified into RDW-quartiles, increased RDW values were accompanied by decreased serum iron levels and hematimetric indices (P < 0.01), whereas age and inflammatory markers increased according to RDW-quartiles (P < 0.001 and P < 0.05, respectively). However, plasma lipids did not change with increasing RDW-quartiles (P > 0.05). In the linear regression analysis, age, hemoglobin, MCV (beta coefficient: 0.202, -0.234, -0.316, P < 0.001) and fibrinogen (beta coefficient: 0.059, P = 0.048) were the only independent predictors of RDW. The present study indicates that RDW is associated with inflammatory markers and hematimetric indices, but not with plasma lipid levels in a healthy population.