Aplastic anaemia: a review

Aplastic anaemia is featured by bone marrow hypocellularity and peripheral pancytopenia and is a potentially fatal disease. In recent years, insight in it pathogenesis has increased. It appears that activated autoreactive T lymphocytes induce apoptosis of haematopoietic stem cells resulting in a hypocellular bone marrow. Nowadays, it can be treated by stem cell transplantation or immunosuppressive therapy. This review focuses on the pathophysiology and treatment of aplastic anaemia

Somatostatin receptor scintigraphy in malignant lymphoma

The prognosis of patients with malignant lymphomas has improved over the last 30 years. Besides from improvements in therapy the better outcome of these patients has resulted also from the introduction of better diagnostic techniques detecting involved sites. Diagnostic radiology plays an essential role in assessing the extent of disease. Imaging studies are also important in assessing the response to treatment, evaluating complications of treatment and demonstrating relapse of disease. Imaging techniques that are frequently used include: conventional frontal and lateral chest radiographs, computed tomography (CT) scanning, ultrasound and magnetic resonance imaging (MRI). The choice of the techniques preferably used is based on patterns of dissentination of the disease and the diagnostic accuracy of the test in terms of sensitivity and specificity. However, factors such as patient acceptance, availability of expertise and equipment and cost may also play a role. Accurate staging and re-staging is critical to the selection of treatment in the interest of improved outcomes. Currently, about 2500 new cases of malignant lymphomas per annum occur in the Netherlands. Approximately 80% of cases are non-Hodgkin's lymphomas (NHL) and the other cases are Hodgkin's disease (HD).There are considerable differences between HD and NHL as regards pathogenesis, pathobiology, clinical presentation, response to therapy and prognosis

Inclusion in morning meetings

This thesis explores the extent to which teachers implement best practice of inclusion during their daily Morning Meetings. Morning Meetings are a standard practice at the beginning of the school day where student and teachers greet one another, share personal stories and information, participate in a group activity, and read a morning message written by the teachers. Preschool through third grade teachers in local school districts were given a self-reflection survey. The survey was a standardized checklist that was informed by research on inclusive practices and The Morning Meeting Book (Kriete & Davis, 2014). It was modeled after the Division for Early Childhood (DEC) and the National Association for the Education of Young Children (NAEYC) joint early childhood inclusion policy, which states the defining features of inclusion as access, participation, and supports (2009). The survey lists specific practices that teachers may or may not be implementing that promote inclusion. My hypothesis before the research began was that teachers would struggle to implement the practices that take more time and preparation outside of their normal routine. The analysis of the data showed that my hypothesis was correct to some extent, teachers were more successful when implementing accommodations that they could plan into the whole group, and less successful with one-on-one accommodations that required them to work individually with a student outside of the Morning Meeting

Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial

Background: Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC). Methodology: From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared. Principal Findings: The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No lifethreatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events. Conclusions: In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was nonsignificant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients. Trial Registration: ClinicalTrials.gov NCT00122642

Integrated Index of Women's Participation in Agricultural Community by Prefecture

textabstractObjective: Anti-Tr is among the better described autoantibodies in paraneoplastic cerebellar degeneration (PCD) combined with Hodgkin lymphoma (HL); however, the Tr antigen remains unidentified. Methods: We used immunoprecipitation of total rat brain extract followed by mass spectrometry to identify the antigen recognized by anti-Tr-positive sera. By Western blotting and cell-based assays, we tested a total of 12 anti-Tr-positive and 246 control sera and determined the region of the epitope recognized by the anti-Tr antibodies. Deletion and mutant constructs were generated to further map the antigenic region. Results: Mass spectrometry analysis of immunopurified rat brain extract using 4 different anti-Tr-positive sera led to the identification of Delta/Notch-like epidermal growth factor-related receptor (DNER) as the Tr antigen. All but 1 of 246 control samples were negative in the HeLa cell-based screening assay, whereas 12 of the 12 anti-Tr-positive sera stained hemagglutinin-tagged DNER-expressing cells. Only 1 control subject with HL but no ataxia was found to be both DNER and Tr positive. Using deletion constructs, we pinpointed the main epitope to the extracellular domain. Knockdown of endogenous DNER in hippocampal and N-glycosylation mutations abolished the anti-Tr staining, indicating that glycosylation of DNER is required for it to be recognized by anti-Tr antibodies. Interpretation: DNER is the antigen detected by anti-Tr-positive sera. Presence of anti-Tr antibodies in patients with PCD and HL or HL only can now be screened quickly and reliably by using a cell-based screening assay

Reproducibility of Gene Expression Signatures in Diffuse Large B-Cell Lymphoma

SIMPLE SUMMARY: Multiple gene expression signatures with biological or prognostic subgroups have been published in diffuse large B-cell lymphoma (DLBCL). With exception of the cell of origin (COO) classifier, these were not validated in independent cohorts. The aim of the study was to reproduce four gene expression signatures capturing multiple biological subgroups using the NanoString platform. In addition, we aimed to identify potential associations between the signatures and portray the heterogeneity of DLBCL. We show that, in an independent cohort of clinically well-defined patients, these signatures can co-occur in the same patient and that each classifier captures a different aspect of the biological heterogenous panorama of DLBCL. Beside COO, there is clear evidence of different immune and MYC signatures. A direct comparison in our cohort showed that these signatures reflect independent biological features. More comparative studies with gene expression profiles need to be conducted to enable a further integration and to help develop new taxonomy systems for clinical utility. ABSTRACT: Multiple gene expression profiles have been identified in diffuse large B-cell lymphoma (DLBCL). Besides the cell of origin (COO) classifier, no signatures have been reproduced in independent studies or evaluated for capturing distinct aspects of DLBCL biology. We reproduced 4 signatures in 175 samples of the HOVON-84 trial on a panel of 117 genes using the NanoString platform. The four gene signatures capture the COO, MYC activity, B-cell receptor signaling, oxidative phosphorylation, and immune response. Performance of our classification algorithms were confirmed in the original datasets. We were able to validate three of the four GEP signatures. The COO algorithm resulted in 94 (54%) germinal center B-cell (GCB) type, 58 (33%) activated B-cell (ABC) type, and 23 (13%) unclassified cases. The MYC-classifier revealed 77 cases with a high MYC-activity score (44%) and this MYC-high signature was observed more frequently in ABC as compared to GCB DLBCL (68% vs. 32%, p < 0.00001). The host response (HR) signature of the consensus clustering was present in 55 (31%) patients, while the B-cell receptor signaling, and oxidative phosphorylation clusters could not be reproduced. The overlap of COO, consensus cluster and MYC activity score differentiated six gene expression clusters: GCB/MYC-high (12%), GCB/HR (16%), GCB/non-HR (27%), COO-Unclassified (13%), ABC/MYC-high (25%), and ABC/MYC-low (7%). In conclusion, the three validated signatures identify distinct subgroups based on different aspects of DLBCL biology, emphasizing that each classifier captures distinct molecular profiles

Risk of heart failure in survivors of Hodgkin lymphoma: Effects of cardiac exposure to radiation and anthracyclines

Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n 5 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n 5 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (Pdifference 5 .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (Ptrend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (Pinteraction 5 .09). Twenty-five–year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up