The WHO 2016 diagnostic criteria for Acute Myeloid leukemia with myelodysplasia related changes (AML-MRC) produce a very heterogeneous entity: A retrospective analysis of the FAB subtype RAEB-T.

We studied 79 patients with AML-MRC or RAEB-T, who were later reclassified according to the WHO classification. Marrow slides were examined cytomorphologically with regard to dysplasia. Patients were followed up until March 2020. Thirty-one patients underwent allogeneic stem cell transplantation (median survival (ms) 16 months), 14 were treated with induction chemotherapy (ms 8.4 months), 18 received hypomethylating agents (ms 9.2 months), 16 received low dose chemotherapy or best supportive care (ms 2.4 months). Only 30.4 % fulfilled the morphologic WHO criteria. 46.8 % were classified as AML-MRC by an antecedent MDS, 54.4 % of the pts were classified by MDS-related chromosomal abnormalities. 5 % did not fulfill any of the criteria and were entered based on 20-29 % medullary blasts. There was no difference in ms between pts presenting with > 50 % dysplasia as compared to pts with dysplasia between 10 % and 50 % (ms 9.1 vs 9.9 months, p = n.s.) or for pts with antecedent MDS (ms 9.1 vs 8.9 months, p = n.s.). Myelodysplasia-related cytogenetic abnormalities were associated with a worse outcome (ms 8.1 vs 13.5 months, p = 0.026). AML-MRC in its current definition is a heterogenous entity. Dysplasia of ≥ 50 % in ≥ two lineages is not helpful for diagnostics and prognostication and therefore should be deleted in future classifications. We recommend utilizing the WHO guidelines for defining dysplasia (10 % or greater in ≥ 1 of the three myeloid cell lines) assisting in establishing the diagnosis of MDS.

A Case of Acute Eosinophilic Leukemia with a Novel PHF6 Mutation.

Acute eosinophilic leukemia (AEL) is a rare form of acute myeloid leukemia (AML) that requires prompt exclusion of reactive etiologies of eosinophilia and identification of an underlying acute myeloid neoplasm. Myeloid neoplasms with prominent eosinophilia often have rearrangements in the platelet-derived growth factor receptor α (PDGFRA) or ß (PDGFRB) or are associated with core-binding factor AML. In this report, we describe a 35-year-old male presenting with chest discomfort and altered mental status, found to have marked leukocytosis with eosinophilic predominance and an elevated blast count. Bone marrow aspirate and biopsy findings were morphologically consistent with AEL. Fluorescence in situ hybridization (FISH) and standard karyotype analysis did not reveal any abnormalities, and mutation analysis using next generation sequencing (NGS) revealed a pathogenic mutation in PHF6. Cardiac work-up revealed findings suggestive of eosinophilic myocarditis. High-dose glucocorticoid therapy was initiated followed by standard intensive induction chemotherapy with cytarabine and idarubicin. He experienced a rapid reduction in peripheral blood eosinophil and blast count and was found to be in a complete remission at the time of his postinduction bone marrow examination. He underwent allogeneic stem cell transplantation with a matched sibling donor after consolidative high-dose cytarabine and remains in remission at the time of this report, 6 months following his initial diagnosis. The rarity of this condition has resulted in a paucity of data to guide management. Additional studies are needed to better characterize this entity and inform optimal management strategies to attain a long-term sustained remission in these patients.

Publisher Correction: GloPL, a global data base on pollen limitation of plant reproduction.

J. H. Burns was omitted in error from the author list of the original version of this Data Descriptor. This omission has now been corrected in both the HTML and PDF versions.

GloPL, a global data base on pollen limitation of plant reproduction.

Plant reproduction relies on transfer of pollen from anthers to stigmas, and the majority of flowering plants depend on biotic or abiotic agents for this transfer. A key metric for characterizing if pollen receipt is insufficient for reproduction is pollen limitation, which is assessed by pollen supplementation experiments. In a pollen supplementation experiment, fruit or seed production by flowers exposed to natural pollination is compared to that following hand pollination either by pollen supplementation (i.e. manual outcross pollen addition without bagging) or manual outcrossing of bagged flowers, which excludes natural pollination. The GloPL database brings together data from 2969 unique pollen supplementation experiments reported in 927 publications published from 1981 to 2015, allowing assessment of the strength and variability of pollen limitation in 1265 wild plant species across all biomes and geographic regions globally. The GloPL database will be updated and curated with the aim of enabling the continued study of pollen limitation in natural ecosystems and highlighting significant gaps in our understanding of pollen limitation.

Smokers Display Reduced Glucocorticoid Sensitivity Prior to Symptomatic Chronic Disease Development.

Background: Chronic stress plays a critical role in many of today's diseases and causes of death. Tobacco use reliably increases the likelihood of chronic disease development and premature death. In addition, habitual tobacco use elevates risk of chronic inflammatory diseases, and glucocorticoid therapy is often less effective in smokers compared with nonsmokers. Taken together, smokers may develop glucocorticoid insensitivity, thereby removing the body's greatest anti-inflammatory mechanism. Purpose: The purpose of this study was to examine glucocorticoid sensitivity among 24 smokers and 24 age-, sex-, and body mass index-matched never smokers who were clinically healthy individuals (i.e., no diagnosis or medication use for chronic diseases and normotensive). Method: Participants visited the lab after a 12 hr fast, provided a blood sample, and completed a series of psychosocial questionnaires. Smokers continued smoking ad libitum before the lab visit. Group differences in glucocorticoid sensitivity were examined using ANCOVA and repeated with linear mixed model to account for possible dependence among immune outcomes that matching participants on age, sex, and body mass index may have introduced. Results: Prior to clinical disease onset, smokers' peripheral blood mononuclear cells (PBMCs) exhibited reduced glucocorticoid sensitivity as well as a diminished inflammatory response to lipopolysaccharide compared with never smokers' PBMCs; results were identical regardless of statistical modeling used. Conclusions: Cigarette smoking, a self-initiated pharmacological chronic stressor, may provide a unique opportunity to examine early wear and tear on physiological functioning that may lead to chronic disease development. Additional research into PBMCs' intracellular changes must be examined as well as repeating this study in a larger, more heterogeneous population.

Reflections on, and visions for, the changing field of pollination ecology.

Since the launch of Ecology Letters in 1998, the field of Pollination Ecology has changed considerably in its focus. In this review, we discuss the major discoveries across the past two decades. We quantitatively synthesise the frequency by which different concepts and topics appeared in the peer-reviewed literature, as well as the connections between these topics. We then look forward to identify pressing research frontiers and opportunities for additional integration in the future. We find that there has been a shift towards viewing plant-pollinator interactions as networks and towards understanding how global drivers influence the plants, pollinators and the ecosystem service of pollination. Future frontiers include moving towards a macroecological view of plant-pollinator interactions, understanding how ecological intensification and urbanisation will influence pollination, considering other interactions, such as plant-microbe-pollinator networks, and understanding the causes and consequences of extinctions. Pollination Ecology is poised to advance our basic understanding of the ecological and evolutionary factors that shape plant-animal interactions and to create applied knowledge that informs conservation decision making.

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM).

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.

Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998).

Failure to undergo activation-induced cell death due to global dysregulation of apoptosis is the pathogenic hallmark of large granular lymphocyte (LGL) leukemia. Consequently, immunosuppressive agents are rational choices for treatment. This first prospective trial in LGL leukemia was a multicenter, phase 2 clinical trial evaluating methotrexate (MTX) at 10 mg/m(2) orally weekly as initial therapy (step 1). Patients failing MTX were eligible for treatment with cyclophosphamide at 100 mg orally daily (step 2). The overall response in step 1 was 38% with 95% confidence interval (CI): 26 and 53%. The overall response in step 2 was 64% with 95% CI: 35 and 87%. The median overall survival for patients with anemia was 69 months with a 95% CI lower bound of 46 months and an upper bound not yet reached. The median overall survival for patients with neutropenia has not been reached 13 years from study activation. Serum biomarker studies confirmed the inflammatory milieu of LGL but were not a priori predictive of response. We identify a gene expression signature that correlates with response and may be STAT3 mutation driven. Immunosuppressive therapies have efficacy in LGL leukemia. Gene signature and mutational profiling may be an effective tool in determining whether MTX is an appropriate therapy.

Reaction pathways for pyridine adsorption on silicon (0 0 1).

Density functional theory is used to describe the reactions of chemisorption of pyridine on the silicon (0 0 1) surface. Adsorption energies of six relevant structures, and the activation energies between them are reported. We consider in detail the dative to tight-bridge transition for which conflicting results have been reported in the literature, and provide a description of the formation of inter-row chains observed in high-coverage experiments. We demonstrate that the choice of DFT functional has a considerable effect on the relative energetics and of the four DFT functionals considered, we find that the range-separated hybrid ωB97X-D functional with empirical dispersion provides the most consistent description of the experiment data.

Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS.

Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

Monosomal karyotype in MDS: explaining the poor prognosis?

Monosomal karyotype (MK) is associated with an adverse prognosis in patients in acute myeloid leukemia (AML). This study analyzes the prognostic impact of MK in a cohort of primary, untreated patients with myelodysplastic syndromes (MDS). A total of 431 patients were extracted from an international database. To analyze whether MK is an independent prognostic marker in MDS, cytogenetic and clinical data were explored in uni- and multivariate models regarding overall survival (OS) as well as AML-free survival. In all, 204/431 (47.3%) patients with MK were identified. Regarding OS, MK was prognostically significant in patients with ≤ 4 abnormalities only. In highly complex karyotypes (≥ 5 abnormalities), MK did not separate prognostic subgroups (median OS 4.9 months in MK+ vs 5.6 months in patients without MK, P=0.832). Based on the number of abnormalities, MK-positive karyotypes (MK+) split into different prognostic subgroups (MK+ and 2 abnormalities: OS 13.4 months, MK+ and 3 abnormalities: 8.0 months, MK+ and 4 abnormalities: 7.9 months and MK+ and ≥ 5 abnormalities: 4.9 months; P<0.01). In multivariate analyses, MK was not an independent prognostic factor. Our data support the hypothesis that a high number of complex abnormalities, associated with an instable clone, define the subgroup with the worst prognosis in MDS, independent of MK.

Evolving trends in the treatment of low-risk myelodysplastic syndromes: immunomodulation and beyond--9th European Hematology Association Congress Geneva, Switzerland, 10-13 June 2004.

The 9th European Hematology Association Congress, held in Geneva, Switzerland, from 10 through 13 June 2004, offered a number of educational programmes that focused on myelodysplastic syndromes (MDS). This report will summarize the material presented at the educational symposium entitled 'Evolving Trends in the Treatment of Low-Risk MDS: Immunomodulation and Beyond'. The overview of the presentations includes a comparative review of the classification systems for MDS; a discussion of treatment strategies and management issues for patients in lower risk disease categories; a description of a novel class of immunomodulators, the IMiDs((R)), and a presentation of updated data from clinical trials of the IMiD compound, lenalidomide, in the treatment of MDS.

Who should perform laparoscopic cholecystectomy? A 10-year audit.

BACKGROUND: Laparoscopic cholecystectomy is one of the most common operations in general surgery. It is performed by surgeons with a specialist interest in biliary disease as well as by surgeons with other specialist interests. METHODS: This retrospective audit of all cholecystectomies was conducted in a single hospital over a 10-year period from 1996 to 2005. Data were extracted from two independent electronic databases and supplemented by a full note review of cases with extended postoperative stay or unplanned readmission. The outcomes for cases under the care of specialist upper gastrointestinal (GI) consultants were compared with outcomes for cases of general surgery consultants from other firms. RESULTS: Data from 4,139 cholecystectomies were obtained. More cholecystectomies performed by upper GI firms were completed laparoscopically (96.2% vs 80.1%) with a higher rate of intraoperative cholangiograms (83.4% vs 16.9%). The mean operating time was shorter for upper GI cases (69 vs 84 min), as was the postoperative hospital stay (2 vs 3.6 days). There also was a significantly lower incidence of bile duct injury in upper GI cases (0.1% vs 0.9%). CONCLUSION: In their institution, the authors found evidence of improved outcomes when laparoscopic cholecystectomy was performed under the care of surgeons with a specialist interest in upper GI or hepatopancreaticobiliary surgery.

Organization of the clinical activity of geriatric oncology: report of a SIOG (International Society of Geriatric Oncology) task force.

Management for elderly cancer patients world wide is far from being optimal and few older patients are entering clinical trials. A SIOG Task Force was therefore activated to analyze how the clinical activity of Geriatric Oncology is organized. A structured questionnaire was circulated among the SIOG Members. Fifty eight answers were received. All respondents identified Geriatric Oncology, as an area of specialization, however the organization of the clinical activity was variable. Comprehensive Geriatric Assessment (CGA) was performed in 60% of cases. A Geriatric Oncology Program (GOP) was identified in 21 centers, 85% located in Oncology and 15% in Geriatric Departments. In the majority of GOP scheduled case discussion conferences dedicated to elderly cancer patients took regular place, the composition of the multidisciplinary team involved in the GOP activity included Medical Oncologists, Geriatricians, Nurses, Pharmacists, Social Workers. Fellowships in Geriatric Oncology were present in almost half of GOPs. Over 60% of respondents were willing to recruit patients over 70 years in clinical trials, while the proportion of cases included was only 20%. Enrolment in clinical trials was perceived as more difficult by 52% and much more difficult in 12% of the respondents. In conclusion, a better organization of the clinical activity in Geriatric Oncology allows a better clinical practice and an optimal clinical research. The GOP which can be set up in the oncological as well as in the geriatric environment thought a multidisciplinary coordinator effort. Future plans should also concentrate on divisions, units or departments of Geriatric Oncology.

The third International Congress on Myeloproliferative and Myelodysplastic Syndromes.

This meeting was convened by Richard T. Silver and co-chaired by Jerry L. Spivak. It was held from 27 to 29 October 2005 in Washington, DC. Thirty-one invited speakers from seven different countries participated in the conference, which was attended by more than 300 individuals from 23 countries. As in previous years, a clinical symposium for patients, held the day before the symposium, was sponsored by the Cancer Research and Treatment Fund, Inc., New York, NY 10021. This meeting report provides a summary of the five sessions prepared and highlighted by one of the session chairs. In addition to the formal presentations on the biology, clinical aspects and management of these diverse marrow stem cell disorders, there was considerable interest generated because of the availability of several new agents that have been recently approved. A special luncheon satellite symposium was devoted to the dramatic changes in the therapeutic options for the myelodysplastic syndromes, sponsored by MGI Pharma, Inc. The keynote address was presented by Dr. George Q. Daley from Harvard Medical School and the Children's Hospital Medical Center. He reviewed the molecular steps in the formation of the Philadelphia chromosome and some of the newly described mutations leading to resistance to chemotherapy (see Section 4).

Phase II study of theophylline in chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E4998).

The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate (cAMP). In 25 patients with Rai stages 0-I, theophylline, 200 mg given orally every 12 h was well tolerated. There was one complete response after 22.5 months of treatment, which continues at 27+ months, and 18 other patients had stable disease. In vitro exposure of patients' lymphocytes to aminophylline (75-250 microg/ml), the soluble form of theophylline, resulted in dose- and time-dependent induction of apoptosis in 9/20 patients studied. Apoptosis was documented flow-cytometrically by monitoring the expression of bcl-2 and bax, forward light scatter, fluorescence intensity of binding of CD45 antibody, and the binding of annexin. Patients whose leukemic lymphocytes were susceptible to apoptosis induction by aminophylline in vitro experienced a significantly longer progression-free survival than patients whose cells were resistant to the drug in culture (P=0.025). This suggests that in a CLL population treated with theophylline, induction of an apoptotic response to the drug in vitro is prognostic for absence of clinical progression.