De novo acute myeloid leukemia with 20-29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study.

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged >50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10-19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2. FLT3 and NPM1 mutations and monocytic morphology occurred more commonly in AML30 than in RAEBT. RAEBT patients were treated less often with induction therapy than AML30, whereas allogeneic stem cell transplant frequency was similar. The median and 4-year OS of RAEBT patients were longer than those of AML30 patients (20.5 vs 12.0 months and 28.6% vs 20.4%, respectively, P = 0.003); this difference in OS was manifested in patients in the intermediate UKMRC karyotype risk group, whereas OS of RAEBT patients and AML30 patients in the adverse karyotype risk group were not significantly different. Multivariable analysis showed that RAEBT (P < 0.0001), hemoglobin (P = 0.005), UKMRC karyotype risk group (P = 0.002), normal BM karyotype (P = 0.004), treatment with induction therapy (P < 0.0001), and stem cell transplant (P < 0.0001) were associated with longer OS. Our findings favor considering de novo RAEBT as a favorable prognostic subgroup of AML.

Management of paroxysmal nocturnal hemoglobinuria in CALR mutated post-essential thrombocythemia myelofibrosis: A case report.

Paroxysmal nocturnal hemoglobinuria (PNH) results from the loss of erythrocyte surface proteins, leading to complement activation and its spectrum of effects. We explore this case of a 57-year-old man with post-essential thrombocythemia (ET) myelofibrosis (MF) who developed symptomatic anemia with evidence of hemolysis on lab work. While hemolysis was localized to be intramedullary based on workup, the exact diagnosis was undetermined, leading to a prolonged course of steroid therapy to control anemia. The hemolysis was eventually attributed to PNH diagnosed on flow cytometry and the patient was treated with complement inhibitors with eventual failure of therapy. He ultimately underwent a successful hematopoietic cell transplant (HCT) with post-transplantation flow cytometry showing complete resolution of PNH. While PNH has been identified as a progression of myelodysplastic syndromes, the mechanisms of its rare development in myeloproliferative neoplasms are poorly elucidated. Furthermore, its rarity and often vague symptoms make diagnosis and treatment a challenge. This is the second reported case of a JAK2-negative, CALR-positive post-ET MF and the first reported case to be treated with HCT. This case probes for further insight into the clinical significance between MF and PNH, its impact on management, and further consideration for HCT as curative therapy in such patients who fail complement inhibitor therapy.

Comparison of air-fluidized therapy with other support surfaces used to treat pressure ulcers in nursing home residents.

To provide empirical evidence comparing pressure ulcer healing rates between different support surfaces, data were analyzed from eligible residents with pressure ulcers (N = 664) enrolled in the National Pressure Ulcer Long-Term Care Study, a retrospective pressure ulcer prevention and treatment study. Support surfaces were categorized as: Group 1 (static overlays and replacement mattresses), Group 2 (low-air-loss beds, alternating pressure, and powered/non-powered overlays/mattresses), and Group 3 (air-fluidized beds). Calculation of healing rates, using the largest ulcer from each resident, found mean healing rates greatest for air-fluidized therapy (Group 3) (mean = 5.2 cm(2)/week) versus Group 1 (mean =1.5 cm(2)/week) and Group 2 (mean = 1.8 cm(2)/week) surfaces (P = 0.007). Healing rates also were assessed using 7- to 10-day "episodes"; each ulcer generated separate episode(s) that included all ulcers when residents had multiple ulcers. Mean healing rates were significantly greater for Stage III/IV ulcers on Group 3 surfaces (mean = 3.1 cm(2)/week) versus Group 1 (mean = 0.6 cm(2)/week) and Group 2 (mean = 0.7 cm(2)/week) surfaces (Group 2 versus Group 3: P = 0.0211). This finding persisted for ulcers with comparable initial baseline areas (20 cm(2) to 75 cm(2)) on Group 2 and Group 3 surfaces; healing improved on Group 3 surfaces (+2.3 cm(2)/week) versus Group 2 surfaces (-2.1 cm(2)/week, P = 0.0399). Residents on Group 3 (6 out of 82; 7.3%) and Group 1 (47 out of 461; 10.2%) surfaces had fewer hospitalizations and emergency room visits than those on Group 2 surfaces (23 out of 121; 19.0%, P = 0.01) despite significantly greater illness in residents on Group 2 and 3 versus Group 1 surfaces (P is less than 0.0001). Despite limitations inherent in retrospective studies, ulcers on Group 3 surfaces versus Groups 1 and Group 2 surfaces had statistically significant faster healing rates (particularly for Stage III/IV ulcers) with significantly fewer hospitalizations and emergency room visits (Group 3 versus Group 2), despite significantly more illness in residents on Group 2 or Group 3 versus Group 1 surfaces. Episode analyses -- providing greater power, uniform treatment duration, and comparable baseline sizes -- confirmed these findings. Air-fluidized support surfaces represent great healing potential that justifies further exploration.

Molecular genetic characterization of lymphoma: application to cytology diagnosis.

Mature B- and T-cell lymphomas are increasingly being associated with specific genetic alterations; characterization of these changes can sometimes be crucial to both diagnosis and prognosis. Molecular testing encompasses fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based assays, as well as classical cytogenetics. FISH and PCR-based assays can be performed on cytology material without the need for advanced planning for testing with fresh tissue. As many lymphoproliferations are amenable to fine needle aspiration diagnosis, it is important for the cytopathologist to be aware of what testing is feasible in these (sometimes limited) specimens. Here, we review pertinent genetic changes in mature B- and T-cell lymphomas with a focus on those that may be encountered more commonly in cytology specimens.

Primary and secondary drug screening assays for Friedreich ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix for the assembly of iron-sulfur clusters (ISCs), which are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain (ETC). Decreased expression of frataxin or the yeast frataxin orthologue, Yfh1p, is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. Using yeast depleted of Yfh1p, a high-throughput screening (HTS) assay was developed in which mitochondrial function was monitored by reduction of the tetrazolium dye WST-1 in a growth medium with a respiration-only carbon source. Of 101 200 compounds screened, 302 were identified that effectively rescue mitochondrial function. To confirm activities in mammalian cells and begin understanding mechanisms of action, secondary screening assays were developed using murine C2C12 cells and yeast mutants lacking specific complexes of the ETC, respectively. The compounds identified in this study have potential relevance for other neurodegenerative disorders associated with mitochondrial dysfunction, such as Parkinson disease.