Journal articles on the topic '580.956 93'

An experiment was carried out at the Lilliana Dimitrova Horticultural Research Institute in order to evaluate several advanced lines from the National Hybridization Program, and from the Nursery of Regional Resistance Sources of common bean, which were springled with Xanthomonas campestris (Xcp 530) – a highly aggressive bacterial strain. Fifteen varieties with intermediate resistance to the bacteria were selected. The CUT54, XAN 280, and 9356-26 lines were outstanding, showing better results than the control BAT 93.

Background: Although primarily a respiratory illness, COVID-19 involves multiple organs when the disease is severe or critical. Hence, we conducted this study to evaluate the incidence of multiple organ dysfunction in COVID-19 patients and its implications on survival. Methods: A retrospective analysis of laboratory-confirmed COVID-19 patients presenting to our center in Dubai, UAE between April 2020 and July 2020. Data was collected from the electronic medical records and analyzed to evaluate multiple organ damage observed during hospital admission. Findings: Five-hundred patients were studied. Overall mean age was 49.5 years (range 13-94), 76% males, 33% diabetics, 31% hypertensives. 97/500 (19.4%) had evidence of single organ damage; 37/500 (7.4%) had two organ damage; and 105/500 (21%) had more than two organ damage. Acute respiratory distress syndrome was the most prevalent organ damage,153/500 (30.6%); followed by acute cardiac injury, 120/500 (24%); acute kidney injury 107/500 (21.4%); acute liver injury 96/500 (19.2%); septic shock 93/500 (18.6%); disseminated intravascular coagulation 27/500 (5.4%), and heart failure 17/500 (3.4%). We found that in-hospital survival reduced as the number of organs involved increased; only 20% patients survived who had more than 2 organ damage. Also, the chances of survival reduced considerably once other organs were involved in addition to the acute respiratory distress syndrome (91.6% survival in ARDS alone vs. 28.6% survival in ARDS with acute kidney injury vs. 10.4% survival in ARDS with shock/acute cardiac injury/acute kidney injury). Conclusion: Multiple organ dysfunction is common in COVID-19 as 21% had evidence of more than two organ damage in our study. The survival in COVID-19 reduces significantly once multiple organs are involved. Early monitoring and recognition of multiple organ dysfunction is necessary to prevent adverse outcomes and improve survival.

A new configuration of chromizing process was developed by separating Cr powder from NH4Cl. FC220 gray cast iron specimens were chromized in this new experimental setup at 450, 550, 650,750, 850 and 950°C during 13 hours in order to study the possibility of chromizing at “low” temperature. The chromized specimens were examined using Scanning Electron Microscopy (SEM), macro-hardness, micro-hardness, compression test and salt spray test. The results shows that the specimen chromized at 650°C gives the best compromise between the corrosion resistance and the hardness of the FC220 with 1.73 ڌm of thickness of the chromized layer. However, after 13 hours of the process, the hardness of the FC220 specimens decreased considerably from 93 HRB to 64.2 HRB (31%).

From January/2000 to December/2003, 550 diarrheic fecal samples from the children and adults were collected in several geographical regions of Paraná State, Brazil. The enzyme immunoassay showed 120 (21.8%) samples positive for the group A rotaviruses. One hundred and fourteen samples were genotyped by multiplex-nested-PCR assay. The highest frequency (77.5%) of the positive samples (n=93) was observed in the children under 5 years old. Rotavirus diarrhea was more frequent in the cold and dry seasons of the four evaluated years. The most frequent genotypes were: G1 (50.9%), G4 (9.6%), G9 (7.0%), G2 (1.7%), G3 (0.9%), P[ 8] (71.9%), and P[ 4] (3.5%). The P[ 8] G1 (46.5%) and P[ 8] G4 (9.6%) were the main combinations found to P and G genotypes. The mixed infections, characterized by the rotaviruses with more than one genotype G or P, and nontypeable rotavirus were observed in 8.8, 3.5, and 16.7% of the samples, respectively. The identification of the G9 genotype in the rotavirus strains tested along the four years of studies ratifies the emergency of this genotype also in Paraná State, South region of Brazil, as the worldwide.

We synthesized the YBa m Cu 1+m O y superconductors; m = 2, 3, 4, 5 that were Y123 ( YBa 2 Cu 3 O 7-x), Y134 ( YBa 3 Cu 4 O 9-x), Y145 ( YBa 4 Cu 5 O 11-x), Y156 ( YBa 5 Cu 6 O 13-x), by solid state reaction with the Y 2 O 3, BaCO 3 and CuO as the beginning materials. The calcination temperature was 950°C and varied the sintering temperature to be 950°C and 980°C. The resistivity measurement by four-point-probe technique showed that the Tconset of Y123, Y134, Y145, Y156 were at 97, 93, 91, 85 K, respectively. The XRD and Rietveld full-profile analysis method were used and found that the crystal structure was in the orthorhombic with Pmmm space group with the ratio c/a were 3.0, 4.0, 5.0 and 6.0 for Y123, Y134, Y145 and Y156, respectively. The oxygen content was characterized by Iodometric titration. The ( Cu 3+/ Cu 2+ and Oxygen content) were (0.28, 6.83), (0.19, 8.81), (0.13, 10.79), (0.16, 12.92) of Y123, Y134, Y145, Y156, respectively. We also found that the increasing of sintering temperature has reduced the oxygen content and the critical temperature of all samples.

1001 Background: Adjuvant weekly paclitaxel (wP) sequential to anthracyclines improves the outcome of operable node-positive BC patients (pts) [Sparano NEJM 2008, Martin BCRT 2009]; however, most BC pts are currently node-negative at diagnosis. The role of wP in these pts is not well established yet. Methods: Pts aged 18-70, with T1-T3/N0 operable BC and at least one high-risk St Gallen 1998 criteria (size >2 cm, hormone-receptor [HR] negative, grade 2/3, age <35 years,) were eligible. HER2+ pts were allowed, after 792 entered the trial, the study was amended to exclude them. Pts were stratified by site, menopausal status, nodal status diagnostic method (sentinel-node biopsy versus lymphadenectomy) and HR status and randomized to receive FAC x6 (500/50/500 mg/m2 every 3w) or FAC x4→wP x8 (paclitaxel 100 mg/m2 weekly). The primary endpoint was DFS. The trial was designed to detect an absolute 5-y DFS increase of 5% (80% FAC, 85% FAC→wP); a sample size of 1812 evaluable patients (906 per arm) was required to detect this difference (α=0.05, β= 80%). Assuming a drop-out rate of 6%, 1929 pts were required. The first analysis of DFS was planned when a median follow-up of 5 years was reached. Results: Between September 2003 and October 2008, 1925 pts (FAC 974, FAC→wP 951) were randomized. Patient characteristics were well balanced between arms, median age was 50, 73% of pts were HR positive and 9% HER2 positive. 97% of pts with FAC and 85% of pts with FAC→wP completed all treatment as planned. The median dose intensity was 98% with FACx6, 99% with FACx4 and 98% with wP. The most frequent grade 3-4 toxicities (>3% in either arm) with FAC vs FAC→wP were neutropenia (25% vs 22%) with 4% vs 3% of febrile neutropenia, fatigue (3% vs 8%), sensory neuropathy (0 vs 5%), and vomiting (4% in each arm). After a median follow-up of 5.3 years, the proportion of patients disease free is 93% and 90% with FAC→wP and FAC (HR for relapse 0.732, 95% CI: 0.542 to 0.990; log-rank p-value=0.0423). Conclusions: For pts with high-risk node-negative BC, adjuvant FAC→wP was associated with a small but significant improvement in DFS compared with FAC, with manageable toxicity.

TLR9 plays pivotal role in innate immune responses through upregulation of costimulatory molecules and induction of proinflammatory cytokines like type I interferons including interferon alpha (IFNA). The present study characterized IFNA cDNA and predicted protein sequences in goat and black buck. Response of the PBM cells to TLR9 agonist CpG ODN C and Phorbol Myristate Acetate (PMA) was evaluated by realtime PCR. IFNA coding sequences were amplified from leukocyte cDNA and cloned in pGEMT-easy vector for nucleotide sequencing. Sequence analysis revealed 570 bp, IFNA ORF encoding 189 amino acids in goat and black buck. Black buck and goat IFNA has 92.1% to 94.7% and 93% to 95.6% similarity at nucleotide level, 86.3% to 89.5% and 70.9% to 91.6% identity at amino acid level with other ruminants, respectively. Nonsynonymous substitutions exceeding synonymous substitutions indicated IFNA evolved through positive selection among ruminants. In spite of lower total leukocyte count, the innate immune cells like monocytes and neutrophils were more in black buck compared to goat. In addition, CpG ODN C-stimulated PBM cells revealed raised IFNA transcript in black buck than goat. These findings indicate sturdy genetically governed immune system in wild antelope black buck compared to domestic ruminant goat.

Following previous reports of impaired physical and intellectual growth, hearing deficit, hypothyroidism, and hyperendemic goiter in Kiga, and the administration of iodized oil injection, this study was conducted to evaluate whether or not the effect of the injection could be sustained by iodized salt supplementation. In 1989, one mL of iodized oil solution containing 480 mg of iodine was injected in 198 schoolchildren aged 8 to 14 years. Four years later, in 1993, iodized salt consumption was begun and has since been continued. Serum thyroid hormones, RT3 uptake and thyroid-stimulating hormone (TSH) were measured before, and three, four, and six years after intervention (1989, 1992, 1993, and 1995). Assessment of urinary iodine was performed by the Foss method at the same intervals mentioned above. Prior to the injection, 94% had grade 2 goiters; four years after injection, 26% and 41% had grades 2 and 1 respectively, and 30% had no goiter (p < 0.001). Two years after the introduction of iodized salt consumption, 5 and 39% had grades 2 and 1 goiter, and 56% were not goiterous. Urinary iodine was 11.4 ± 19.8 mug/L before intervention, and was increased to 93 ± 66 and 92 ± 34 mug/L, three and four years, respectively, after intervention. Two years after iodized salt consumption it was 161 ± 34 mug/L. Mean serum T4 was 5.0 ± 2.0, 9.6 ± 2.0, 9.6 ± 2.0 and 9.2 ± 1.5 mug/dL; serum TSH was 20.3 ± 22.8, 2.1 ± 1.9, 2.5 ± 1.6 and 2.9 ± 1.7 mU/L; before and three, four, and six years after the beginning of the study. All children were euthyroid after three, four, and six years of study. Findings show the benefits of iodized oil administration in decreasing goiter size and in reversing abnormal thyroid function. These effects are sustained by iodized salt consumption in schoolchildren who had been previously hypothyroid due to iodine deficiency.

Une typologie des élevages de cerfs a été réalisée grâce à la méthode graphique de Bertin. Quatre grands types d'élevage qui se différenciaient essentiellement selon la superficie des pâturages, le chargement moyen et l'intensification des pratiques d'élevage ont pu être distingués. La campagne d'abattage de 1994 totalisait 1 053 têtes dont 927 ont été concernées par le suivi. Les cerfs abattus étaient des mâles entiers (93 %). Trente-cinq pour cent de l'effectif étaient âgés entre 1 et 2 ans et 48 % avaient plus de 2 ans. Le pourcentage de carcasses déclassées était de 1,6 % chez les éleveurs ayant opté pour la pesée comme outil de tri ; chez les autres éleveurs, il était sept fois plus important (12 % ; différence significative p < 0,001). Le poids vif (PV) moyen des cerfs abattus (n = 510) était de 49,0 + ou - 0,6 kg, le poids carcasse (PC) moyen (n = 927) à chaud après égouttage était de 28,4 + ou - 0,3 kg et le rendement à chaud (RD) moyen était de 56,8 + ou - 0,3 %. Des analyses de la variance conduites sur les variables PV, PC et RD montrent que les facteurs types d'élevage, âge et saison d'abattage avaient un effet significatif. L'effet type d'élevage ne permet pas de discriminer un type d'exploitation plus performant. Les élevages extensifs (type 4) avaient des performances plus faibles par manque de finition de leurs animaux. De 1 à 2 ans, le PC a augmenté de 6 kg (25 kg/31 kg) mais le RD a diminué de 2 %, de 58 à 56 %. La meilleure saison d'abattage était la saison fraîche avec des carcasses de 30 kg et un rendement de 57 %. Une équation de régression significative (p < 0,001) permet de prédire le PC en fonction de PV [PC(kg) = 0,5 PV(kg) + 3,4]. Vis-à-vis des autres pays éleveurs de cerfs rusa, les performances d'abattage obtenues en Nouvelle-Calédonie étaient moins bonnes. Cette différence de niveau de performance est à rattacher au mode d'élevage plus extensif du cerf rusa en Nouvelle-Calédonie. L'amélioration du niveau de production semble liée à une meilleure stratégie alimentaire pendant la saison sèche et à la finition des jeunes mâles abattus avant deux ans.

9576 Background: Advanced care planning is an essential component of cancer care for patients with incurable malignancies. However, the extent to which clinicians clearly document end-of-life care discussions and code status preferences in ambulatory medical records is unknown. The goal of the study was to investigate the rate of code status documentation in the electronic longitudinal medical record (LMR) of patients with metastatic cancers. Methods: We conducted a retrospective review of outpatient medical records of 2498 patients with metastatic solid tumors seen at an academic cancer center from 10/1/06 through 2/29/08. An electronic database was used to gather information on patient demographics, cancer type, and visits to the cancer center. The sample consisted of patients with metastatic breast, colorectal, non-colorectal gastrointestinal (GI), bladder/kidney, ovarian, prostate, and lung cancers. For the study endpoints, we queried the LMR to determine completion and designation of code status, which could be documented as follows: full code, do not resuscitate (DNR)/do not intubate (DNI), or DNR/DNI with specific resuscitation requests. Multiple logistic regression was used to identify independent predictors of code status completion and resuscitation preference. Results: Among the 2498 patients, 508 (20.3%) had a documented code status. Code status was documented more frequently in patients with metastatic non-colorectal GI (193/609, 31.7%) and lung (179/583, 30.7%) cancers compared to patients with genitourinary malignancies (bladder/kidney [4/89, 4.5%], ovarian [4/93, 4.3%] and prostate [7/365, 1.9%] cancers). Independent predictors of having documented code status included cancer type and a greater number of visits to the cancer center. Younger patients and black patients were less likely to be designated as DNR/DNI. Conclusions: Despite the incurable nature of metastatic cancers, a minority of patients had a code status documented in the outpatient medical record. Given the importance of advanced care planning for those with terminal illness, interventions are needed to encourage discussion and documentation of end-of-life care preferences in patients with advanced cancer. No significant financial relationships to disclose.

9561 Background: To assess melanoma specific health-related quality of life (HRQoL) and health states in patients with earlier stage metastatic (IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma. Methods: Data were collected from the Adelphi Real World Advanced Melanoma Disease-Specific Programme, a cross-sectional survey of 112 physicians and their patients (N = 666). Data were collected between March and July 2016 in the US. A subset of 183 patients completed the Functional Assessment of Cancer Therapy Melanoma (FACT-M) and EuroQol-5D (EQ-5D) one time. Patients were classified by stage of melanoma at time of consultation. Descriptive analyses of HRQoL scores between earlier and late stage metastatic melanoma were assessed using Mann-Whitney U tests. Results: The mean age of the earlier stage and late stage metastatic patients was 62 and 64 respectively. More earlier stage metastatic patients had an ECOG status of 0 or 1 versus late stage metastatic patients (85%, 75% respectively). A total of 31% of late stage metastatic patients required caregiver support and had a median time since primary diagnosis of 5.0 months whereas earlier stage metastatic patients reported 14% and 5.2 months respectively. Patients with earlier stage metastatic melanoma had better mean EQ-5D index scores versus late stage metastatic melanoma patients (0.81 (n = 84), 0.76 (n = 93); p = 0.0103). Higher scores indicating better HRQoL were observed between earlier stage metastatic versus late stage metastatic melanoma patients for the FACT-M (120.7 (n = 81), 107.4 (n = 91); p = 0.0017) and subscales (except Social Well Being). Clinically meaningful differences between groups using published minimal important differences (MIDs) were observed in in 6/7 FACT-M subscales and EQ-5D VAS. Conclusions: Differences in HRQoL and health states were observed between earlier stage metastatic and late stage metastatic melanoma populations, highlighting the detrimental effect of developing metastatic disease. These results suggest that treatments that delay progression of the disease are important to conserve patients HRQoL

9564 Background: Chemotherapy may induce anemia with potentially severe consequences. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study examined the efficacy and safety of epoetin alfa biosimilars (EABs) for the treatment of chemotherapy-induced anemia (CIA) in the clinical setting. Methods: ORHEO was a multicenter, observational, prospective, post-marketing study conducted in France. Patients with CIA (Hb <110g/L) >18 years old, with solid tumors, lymphomas or myelomas and eligible for epoetin alfa treatment were included in the study; they received EAB as prescribed by their physician. Baseline patient characteristics and anemia-related data including baseline and target Hb level epoetin treatment, adverse events and any other concomitant treatments prescribed were recorded. The primary endpoint was the rate of responders (defined as an increase in Hb levels to 100 g/L or at least 10 g/L since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M3). Other endpoints included rate of responders at +6 months (M6) and safety endpoints. Results: 2310 patients (51.43 % male, 48.57 % female) from 232 centers were included in this study. At baseline 79.6% had solid tumors, 13.0% lymphomas and 7.4% myelomas. Median age was 68 y (range: 18–93). Mean baseline Hb level was 96 g/L with a target Hb level of >= 120 g/L for 52.7% of patients. Almost all (99.9%) received the biosimilar epoetin zeta (median dose 30,000 IU/week) with 26.6% receiving additional iron supplementation. A total of 2056 and 1664 patients had at least one Hb level value at M3 and M6 respectively. The rate of response was 81.6% and 86.5% at M3 and M6, respectively. In total, 17.0% of treated patients reported clinically relevant adverse events (all grades), the most common being infections (5.0%) and thromboembolic events (3.5%). Transfusion rates were reported as 9.4% and 5.8% at M3 and M6, respectively. No EAB-related deaths were reported. Conclusions: EAB was effective and well-tolerated in the management of CIA. Clinical trial information: NCT01626547.

ObjectiveTo estimate the economic burden to the health service of surgical site infection following caesarean section and to identify potential savings achievable through implementation of a surveillance programme.DesignEconomic model to evaluate the costs and benefits of surveillance from community and hospital healthcare providers’ perspective.SettingEngland.ParticipantsWomen undergoing caesarean section in National Health Service hospitals.Main outcome measureCosts attributable to treatment and management of surgical site infection following caesarean section.ResultsThe costs (2010) for a hospital carrying out 800 caesarean sections a year based on infection risk of 9.6% were estimated at £18 914 (95% CI 11 521 to 29 499) with 28% accounted for by community care (£5370). With inflation to 2019 prices, this equates to an estimated cost of £5.0 m for all caesarean sections performed annually in England 2018–2019, approximately £1866 and £93 per infection managed in hospital and community, respectively. The cost of surveillance for a hospital for one calendar quarter was estimated as £3747 (2010 costs). Modelling a decrease in risk of infection of 30%, 20% or 10% between successive surveillance periods indicated that a variable intermittent surveillance strategy achieved higher or similar net savings than continuous surveillance. Breakeven was reached sooner with the variable surveillance strategy than continuous surveillance when the baseline risk of infection was 10% or 15% and smaller loses with a baseline risk of 5%.ConclusionSurveillance of surgical site infections after caesarean section with feedback of data to surgical teams offers a potentially effective means to reduce infection risk, improve patient experience and save money for the health service.

Abstract Background Adrenal insufficiency (AI) is a life-threatening disease characterized by deficient production of glucocorticoids and/or mineralocorticoids. It is caused by primary or secondary/tertiary adrenal failure. Prompt diagnosis and management are essential and may even be life-saving. Methods We retrospectively collected clinical, laboratory and radiological data from AI patients observed over 34 years (1984–2017) in a pediatric endocrinology department of a tertiary care hospital. Results Seventy AI patients were identified: 59% with primary adrenal insufficiency (PAI) and 41% with central adrenal insufficiency (CAI). PAI patients were diagnosed at 1.5 ± 4.4 years and followed for 11.6 ± 6.2 years; 85% had classical congenital adrenal hyperplasia (CAH) and 7% had autoimmune PAI. At presentation, 73% had hyponatremia and more than half had mucocutaneous hyperpigmentation, asthenia, anorexia, weight loss, nausea and vomiting. All the patients were treated with hydrocortisone and 90% were also on fludrocortisone. Regarding CAI patients, they were diagnosed at 5.4 ± 5.0 years and they were followed for 9.6 ± 6.4 years; craniopharyngioma was present in 31% of the cases and 14% had pituitary hypoplasia. Besides corticotropin, thyrotropin (93%), growth hormone (63%) and antidiuretic hormone (52%) were the most common hormone insufficiencies. The most frequent manifestations were hypoglycemia (34.5%), nausea/vomiting (27.6%) and infectious diseases (27.6%); all the patients were treated with hydrocortisone. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population. Raising awareness and knowledge in medical teams and population about the disease is of crucial importance to improve clinical outcomes and to reduce disease morbidity/mortality.

SummaryObjective: To develop and validate an efficient and accurate method to identify foreign-born patients from a large patient data registry in order to facilitate population-based health outcomes research.Methods: We developed a three-stage algorithm for classifying foreign-born status in HIV-infected patients receiving care in a large US healthcare system (January 1, 2001-March 31, 2012) (n = 9,114). In stage 1, we classified those coded as non-English language speaking as foreign-born. In stage 2, we searched free text electronic medical record (EMR) notes of remaining patients for keywords associated with place of birth and language spoken. Patients without keywords were classified as US-born. In stage 3, we retrieved and reviewed a 50-character text window around the keyword (i.e. token) for the remaining patients. To validate the algorithm, we performed a chart review and asked all HIV physicians (n = 37) to classify their patients (n = 957).We calculated algorithm sensitivity and specificity.Results: We excluded 160/957 because physicians indicated the patient was not HIV-infected (n = 54), “not my patient” (n = 103), or had unknown place of birth (n = 3), leaving 797 for analysis. In stage 1, providers agreed that 71/95 foreign language speakers were foreign-born. Most disagreements (23/24) involved patients born in Puerto Rico. In stage 2, 49/50 patients without keywords were classified as US-born by chart review. In stage 3, token review correctly classified 55/60 patients (92%), with 93% (CI: 84.4, 100%) sensitivity and 90% (CI: 74.3, 100%) specificity compared with full chart review. After application of the three-stage algorithm, 2,102/9,114 (23%) patients were classified as foreign-born. When compared against physician response, estimated sensitivity of the algorithm was 94% (CI: 90.9, 97.2%) and specificity 92% (CI: 89.7, 94.1%), with 92% correctly classified.Conclusion: A computer-based algorithm classified foreign-born status in a large HIV-infected cohort efficiently and accurately. This approach can be used to improve EMR-based outcomes research.Citation: Levison J, Triant V, Losina E, Keefe K, Freedberg K, Regan S. Development and validation of a computer-based algorithm to identify foreign-born patients with HIV infection from the electronic medical record. Appl Clin Inf 2014; 5: 557–570 http://dx.doi.org/10.4338/ACI-02-RA-0013

Abstract Abstract 5180 Alpha-thalassemia (α-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome and hemoglobin H (HbH) disease. HbH disease is characterized by microcytic hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice, and sometimes thalassemia-like bone changes. Diagnostic of Alfa Thalassemia: Classic testing for α-thalassemia includes: hematologic testing of red blood cell indices, peripheral blood smear, supravital stain to detect RBC inclusion bodies, and qualitative and quantitative hemoglobin analysis. HBA1, the gene encoding α1-globin, and HBA2, the gene encoding α2-globin, are the two genes most commonly associated with α-thalassemia. Molecular genetic testing of HBA1 and HBA2 detects deletions in about 90% and point mutations in about 10% of affected individuals. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV, @RSF, @MAF, @LHD% and many morphological parameters for RBC and Reticulocytes calles Cell Population Data. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Alfa Thalassemia. Patient and Methods: We have collected 129 patients with Alfa Thalassemia Intermedia (HbH disease). All of them were confirmed by red cell morphology, Hgb Electroforesis, cromatography in liquid phase in human whole blood for the determination of Hemoglobin A2, F, A1c, and identification of abnormal hemoglobins and DNA analysis (DNA Analysis by GAP-PCR). We have compared these patients with a control group (184 individuals) and with other anemias (see Table 1). Results: Using ROC analysis, the best parameters differentiating the HbH Disease from the normals were: RDW (AUC 1. 000), @LHD(AUC 1. 000), @MAF(AUC 1. 000), @MCNRET (AUC 1. 000), MCV (AUC 0. 999), @MCRET (AUC 0. 999), @RSF (AUC 0. 998), HGB (AUC 0. 996), @MSCV (AUC 0. 995). Using ROC analysis, the best parameters differentiating the HbH Disease from other anemias (excluding normals) were: @LHD(AUC 0. 957), @MCNRET (AUC 0. 946), @MCRET (AUC 0. 902), @MAF(AUC 0. 873), MCV (AUC 0. 869). Using logistic regression we found a discrminant function that permits to differentiate/flag perfectly the patients with HbH disease from other anemias, and of course from normals: AUC 0. 996) Sensitivity: 91. 47% Specificity 94. 68% with a percent of cases correctly classified of: 93. 67 %. Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Novartis: Research Funding, Speakers Bureau; Apopharma: Research Funding, Speakers Bureau; Ferrokin: Research Funding.

Abstract Abstract 2389 Autologous hematopoietic cell transplantation (autoHCT) is standard therapy for high-risk hematologic disorders and solid tumors. We assessed whether overall survival (OS) at Day 100, which represents early transplant-related mortality (TRM), and at one year, which represents disease-related mortality and later TRM, had changed over time. The study population was derived from patients undergoing 68,404 first autoHCTs between 1994–2005 in US and Canadian centers reported to the CIBMTR. Statistical significance was measured using Ptrend over 6 time cohorts to test whether the OS estimates were stable (slope = 0), increasing (slope>0) or decreasing (slope<0) over time. The Day 100 and 1-year OS estimates are shown in the Table. Disease and disease status subgroups were defined a priori, and the OS estimates are not adjusted for any covariates such as age, Karnofsky status, etc. Mortality rates at Day 100 were, in general, low for all diseases examined and improved significantly over time for NHL in complete remission (CR) 2/sensitive 1st relapse, for lymphoma in primary induction failure (no prior complete remission) and myeloma in first partial or complete remission. Improvements in 1-year OS were seen for NHL in CR1/sensitive 1st relapse and myeloma in remission at the time of transplant. OS has improved for many patients undergoing autoHCT which likely reflects improvement in supportive care and better patient selection. Day 100 mortality rates in autoHCT patients treated during the most recent period 2004-5 are as low as 2–5% in patients with chemotherapy sensitive disease pre-autoHCT. Even in patients transplanted with resistant disease (no prior CR), the Day 100 mortality rate is only 5% in MM and 9% in HL/NHL patients. Although the 1-year OS has improved over time there is still a significant decline in OS between the Day 100 and 1-year time points, especially for patients with NHL in CR2/sensitive 1st relapse, lymphoma in primary induction failure and myeloma not in remission, suggesting a need for improved disease control in these patients. Table 1: Overall survival (95% CI) estimates over time. Autologous HCT 1994-5 1996-7 1998-9 2000-01 2002-3 2004-5 Ptrend NHL in CR2/Rel 1 sens N 890 1067 1041 1020 946 1116 <0.001 @100 days 89 (87–91) 90 (88–92) 90 (88–92) 94 (92–95) 94 (92–95) 95 (94–97) <0.001 @1 year 68 (65–71) 69 (66–72) 72 (69–75) 77 (75–80) 78 (75–80) 80 (77–83) HL in CR2/Rel1 sens N 384 384 466 435 477 573 0.4758 @100 days 95 (92–97) 95 (92–97) 96 (94–97) 97 (95–98) 96 (94–98) 97 (95–98) 0.1985 @1 year 86 (82–89) 87 (84–91) 87 (83–90) 89 (85–92) 90 (87–93) 91 (88–93) HL or NHL in PIF N 647 708 772 895 570 504 0.0299 @100 days 86 (84–89) 88 (86–90) 87 (84–89) 90 (87–92) 90 (88–93) 91 (89–94) 0.7532 @1 year 69 (65–73) 69 (65–72) 70 (67–74) 72 (68–75) 71 (67–75) 72 (67–76) MM in CR1/PR1/PIF sens N 267 541 718 1567 2423 3192 <0.001 @100 days 96 (94–98) 96 (94–98) 96 (94–97) 97 (96–98) 98 (97–98) 98 (98–99) <0.001 @1 year 83 (79–88) 84 (81–87) 87 (85–90) 90 (89–92) 92 (91–93) 92 (91–93) MM in less than PR N 105 177 392 420 521 586 0.3829 @100 days 92 (85–96) 94 (90–97) 96 (94–98) 96 (94–98) 97 (95–98) 95 (93–97) 0.0857 @1 year 79 (70–87) 79 (73–85) 86 (82–89) 88 (84–91) 88 (85–91) 87 (84–90) NHL – non-Hodgkin lymphoma, HL – Hodgkin lymphoma, MM – myeloma, CR – complete remission, Rel – relapse, PIF – primary induction failure, sens – sensitive Disclosures: No relevant conflicts of interest to declare.

Abstract BACKGROUND: The diagnosis of monoclonal B-cell lymphocytosis (MBL) is used to characterize patients who have a circulating population of clonal B-cells, a total B-cell count of <5 x 109/L, and no other features of another B-cell lymphoproliferative disorder. In most patients the immunophenotype is similar to that of chronic lymphocytic leukemia with co-expression of CD19 and CD5. The natural history of CLL-phenotype MBL is unclear. We used the Mayo Clinic hematopathology database to identify patients with CLL-phenotype MBL and abstracted clinical information on natural history and prognostic parameters from clinical and research records. METHODS: Using hematopathology records, we identified a cohort of 1820 patients seen at Mayo Clinic between August 1998 and May 2006 who underwent investigation using peripheral blood flow cytometry and who were found to have a clonal B-cell population of CLL phenotype. After elimination of patients with advanced stage (Rai I-IV), previously treated CLL, and individuals with an established diagnosis of CLL/MBL >1 year prior to flow, 636 unique patients with isolated lymphocytosis were identified. Based on our prior analysis (Leukemia Research 32:1458) demonstrating that nearly all patients with an ALC >10x109/L have a B-cell count >5x109/L, we focused the remaining analysis on the 405/636 patients who had an ALC <10x109/L and the necessary raw data from flow cytometry analysis to determine the B-cell count. RESULTS: Among the 405 individuals with an ALC <10x109/L, 306 (76%) had a B-cell count <5x109/L at the time of flow and met the current criteria for the diagnosis of MBL (BJH 130:325). Median age at the time of MBL diagnosis was 70 years (range 34 – 93). A slight male preponderance was observed (59% male). B-cell counts ranged from 0.02 to 4.99x109/L and ALC ranged from 0.3–9.6 x109/L. CD38 status was available for 268 (88%) MBL patients of whom 20% were CD38 positive using the 30% threshold. Cytogenetic analysis by fluorescent in situ hybridization (FISH) was available in 130 (42%) MBL patients. Using the hierarchical classification system of Dohner and colleagues, 57 (44%) were 13q-, 23 (18%) were trisomy 12, 5 (4%) were 11q-, 4 (3%) were 17p-, and 39 (30%) had no defect detected. ZAP-70 status was available for 77 (25%) patients of whom 13% were ZAP-70+ positive. Patients underwent sequential monitoring with a median follow-up of 1.7 yrs (range 0–8.1 yrs). Time from diagnosis to treatment for patients meeting criteria for MBL (n=306) as compared to Rai stage 0 CLL patients with B-cell counts between 5.0 and 10.0 x109/L (n=99) was not significantly different and is shown in Figure 1 (p=0.87). For individuals with MBL, survival free of treatment was 98% (95%CI: 96–100%) at 1 year, 93% (95%CI: 89–98%) at 2 years, and 77% (95%CI: 67–89%) at 5 years. While gender (p=0.10), and B-cell count as a continuous variable (p=0.15) were not found to be associated with time to treatment (TTT) among MBL patients, age (p=0.02, HR=0.94, 95% CI: 0.89–0.99) and CD38 status (p<0.02, HR: 3.3, 95% CI: 1.2–9.2) did show a relationship with TTT. CONCLUSIONS: Although we observed a low rate of progression among individuals meeting criteria for MBL, TFS was similar to individuals meeting current criteria for Rai stage 0 CLL who had B-cell counts between 5.0 – 10.0 x109/L . Among individuals meeting criteria for MBL, younger patients and those who were CD38 positive had a shorter time to treatment. Additional studies are needed to determine what B-cell count or other characteristics should be used to distinguish between MBL and Rai stage 0 CLL. FIGURE: FIGURE:.

Abstract Background. Type 1 diabetes mellitus (T1DM) is an autoimmune disease. A safe induction of an autoimmunity-free status may become a promising therapy. We hypothesize that intense immuno- and myelosuppression followed by autologous hematopoietic stem cell (HSC) rescue is an option to establish a lasting immunetolerance by eliminating auto-reactive lymphocytes and thus facilitate a possible recovery of autologous insulin production. Aims. Evaluate the HSC mobilization, infusion and engraftment in T1DM patients. Patients and Methods. Between January of 2004 and July of 2006 15 T1DM patients (12 male/3 female), with no more than 6 weeks after the first episode of hyperglycemia, were selected and enrolled. Their median age was 17 years old (range 14–31). HSC were mobilized into the peripheral blood (PB) by cyclophosphamide (Cy) 2g/m2 and filgrastim (G-CSF) 10 μg/kg/day. Peripheral blood stem cells (PBSC) were collected by leukapheresis using COBE Spectra (Gambro BCT, Lakewood, CO) blood cell separator. Collected PBSC were mixed with a cryoprotectant solution (autologous plasma and 10% dimethyl-sulfoxide (DMSO)), then frozen and stored in a mechanical freezer (−80°C). The CD34+ cell were counted using the ISHAGE protocol by a FACSort flow cytometer and CellQuest software packages (Becton Dickinson, San Jose, CA, USA). The conditioning regimen was Cy 200mg/kg and anti-lymphocyte globulin (4.5mg/kg). The protocol and the consent form were approved by the institution and the national ethics committees. Results. All results are expressed as median (range), except when specified. The collection was done on the 7th day (7–9) after the chemotherapy. The pre-apheresis values were: WBC (×103/μL) 7.9 (2.6–56.0); Hct (%) 37.4 (30.9–44.7); platelets (×103/μL) 177 (87–295); CD34+ (μL) 80.9 (36.5–167.6). The blood volemia processed and apheresis duration (min) were 2.8 (2.0–3.1) and 235 (177–280), respectively. Five patients (33.3%) experienced mild adverse reactions related to G-CSF administration (osteo-muscular pain and headache) and six (40%) related to citrate infusion (paresthesia and tremors), although thirteen (86%) had received prophylactic intravenous calcium infusion. The final yield values were: volume (mL) 210 (170–273); WBC (×108/Kg) 6.0 (3.0–14.9); Hct (%) 5.0 (3.3–9.0); CD34+ (×106/kg) 9.6 (5.8–22.5). Fourteen patients have already been transplanted. The time between cryopreservation and infusion was 21 days (13–35). The dose of DMSO infused was 0.4 mL/kg (0.0–0.5) (one patient received washed PBSC). All patients presented mild complications related to infusion: 13 (93%) nausea or vomiting, 8 (57%) flushing, 5 (36%) abdominal pain, 4 (29%) headache and 3 (21%) dyspnea, but only one needed oxygen supplementation. None of the patients presented complications like renal failure, hepatic insufficiency or cardiac arrhythmias. The time to reach granulocytes recovery (500/μL) was 9 days (7–10). Conclusions. The present data suggest that HSC mobilization in T1DM patients are very effetive, precocious and provide a good collection of CD34+ cells. The infusion of PBSC is a safe and reliable procedure with a low incidence of severe side effects and early engraftment. These results could be explained by a good bone marrow function as these patients had never been submitted to any kind of myelo or immunosuppressive therapy.

Estimating density, population size and dynamics of Common Buzzard (Buteo buteo) in the West Carpathian region by a new method In the Hornr Ponitrie Region (central Slovakia) during 1991-2001 we conducted a regular survey of Common Buzzard nests. In 2002-2006 our sampling effort increased and within the selected areas we studied buzzard dispersion/distribution, density and population dynamics using a new method of large-scale thorough search for nests with multiple nest check. The method is designed to estimate the dispersion/distribution, density and population size of target species (particularly raptors) at an absolute scale of abundance in large tracts of heterogeneous landscapes for studies of population fluctuations, trophic dynamics, reproductive success, habitat selection and use. It consists of systematic search for nests with extent of several tens of km2 and grain of c. 3000 m2, identifying and positioning the nests, and subsequent 1-3 nest checks during the each of three or more consecutive breeding periods. Further essential features include correct record of nest positions and other variables, combination of nest checks with ringing and marking, proportional sampling in apparently suitable and less suitable areas and proper timing and spacing of nest visits. In 2007 the sampling focused on DSF (Databank of Slovak Fauna) grid square 7377 covering c. 135 km2. We searched 71 km2 in total and estimated the density at 129 pairs/100 km2. Within the district of Prievidza (959 km2) we found 150 active buzzard nests. In 2008 we sampled the grid square 7377 more extensively, including higher altitudes (800-1200 m a. s. l.). Sampling of 82 km2 in total yielded the density estimate of 93 pairs/100 km2. Within the district of Prievidza we found 110 active buzzard nests. The reproductive success over four year period averaged 1.2 fledgling per active nest (n = 310 nests). Our sample enabled us to estimate the minimum population size in the whole grid square 7377 at 130 breeding pairs, i.e. 96 pairs/100 km2. Minimum population size for the whole district of Prievidza can be estimated approximately at 500 breeding pairs (52 pairs/100 km2), c. 350 of which breed in mountain forests, c. 80 in agricultural woodlots, and c. 70 in riparian vegetation. Rough estimate of minimum breeding population in the whole Slovakia is c. 15 000 pairs, i.e. on average 31 pairs/100 km2.

Abstract Background. Mutations in the RARα-region ligand binding domain (LBD) of PML-RARα were detected in 30 – 40% of patients (pts) tested after first relapse from ATRA-chemotherapy (CT) regimens in 2 North American Phase III trials. However, no follow-up data were reported to assess whether this affected subsequent outcome. Methods. In the current study, 8 relapse pts were tested by previously-published techniques for PML-RARα LBD mutations after relapse from ATRA-CT regimens of the EAG. Treatment was according to the APL2000 protocol: randomization to induction with ATRA+DNR with AraC (arm-A) or no AraC (arm-B) followed by 2 consolidation courses with DNR with (A) or without (B) AraC and then 2 years maintenance with ATRA for 15 days every 3 months, as well as, 6MP and MTX (Ades, et al, J Clin Oncology24, 5703, 2006); 1 off-protocol (OP) pt was treated according to APL-93, which is similar to APL2000-A (Fenaux, et al, Blood94, 1192, 1999). Results. Patient Treatment Days to Relapse Days ATRA Maintenance Days Off ATRA PML-RARα LBD Mutation Status Post-Relapse 1-Au APL2000-B 1037 120 173 No CR2 2-An OP like-A 1072 120 210 No CR2 3-Ho APL2000-A 1194 105 529 No CR2 4_Ge APL2000-B 557 90 0 del/ins & R276W Rel1→Dead 5-Lu OP like-93 1249 0 ~1200 No Dead in CR2 6-Ro OP like-A + VP16 992 0 ~950 No CR2 7-Ka APL2000-B 530 45 0 ΔK227→S229/ M227 Rel3→Dead 8-Ma APL2000-B + AraC 406 45 0 R272W & N298S Rel2→CR3 Mutations were observed in the reported incidence range: 3/8 pts (37.5%). However, the findings were unusual, since 2/3 mutations were deletion mutations, while only 2/30 reported mutations were deletions, and since 2/3 pts harbored 2 mutant subclones, while only 1/30 such cases has been reported. Also, the nature of the mutations was unusual. In pt 7, the ΔK227∅S229/M227 mutation was atypically located in the amino-region of the LBD. In pt 4, a very atypical deletion/insertion (del/ins) mutation began in the hinge RARα-region at S157, extending 630 nt to R367, and was associated with a 547 nt insertion from the beginning of intron 4 that changed the translational reading frame, encoding a truncated protein lacking the entire LBD. Most notably, the 3 pts harboring these uncommon mutations either failed to achieve a second complete remission (CR) or suffered subsequent relapses, leading to death in 2 pts from resistant disease (pts 4 & 7), while 0/5 non-mutant pts relapsed (pt 5, death in CR2 was treatment-related). Discussion. With such a small sample size, it is not possible to determine whether the uncommon mutations occurred by chance or related to some unrecognized element in the EAG pts. No readily apparent basis could be identified: the modest treatment dose-schedule differences from other Phase III studies using common therapeutic agents seems an improbable cause; one each of the mutant/non-mutant pts had an extra chromosome (trisomy 8); 2 of the non-mutant cases had treatment-related APL. Although further study is needed to determine whether the poor outcome in 3 pts was related to the uncommon nature of their mutations, these results suggest that testing for PML-RARα mutations at first relapse may be of prognostic and potential therapeutic value.

Abstract Asparaginase (ASP) has a unique role in the treatment of ALL, and several pediatric studies have demonstrated that modifications of schedule, preparation and dose of ASP may have an impact on overall outcome. The optimisation of ASP treatment is therefore an important aim of the German Multicenter Study Group for Adult ALL (GMALL). In 1999 a pilot trial for adult ALL was started (GMALL 06/99), followed by the ongoing main trial 07/2003. Induction comprised dexamethasone, vincristine, daunorubicine and i.th. methotrexate. One dose of pegylated ASP (PEG-ASP) 1000 U/m2 (500 U/m² if > 55yrs) was given instead of 7 doses of 5000 U/m2 native E.coli asparaginase (ASP) given over 14 days in previous GMALL studies. In consolidation one dose PEG-ASP (500 U/m2) replaced one dose of E.coli ASP (10000 U/m2) in combination with high-dose methotrexate (1500 U/m²) and mercaptopurine. ASP activity was above 100 U/l at day 10 in 80% of the pts after 1000U/m2 and in only 42% after 500 U/m2. Based on this correlation between dose and duration of activity in study 07/2003 (amendment II in 12/2006) the dose for PEG-ASP was increased to 2000 U/m2 in induction and consolidation for pts < 55 yrs and to 1000 U/m2 for pts > 55 yrs in order to improve treatment efficacy. Details of the protocol have been reported (Brüggemann, Blood2006: 107;1116). Patients: 959 pts with a median age of 36 yrs are evaluable. 8% (N=82) were older than 55 yrs. Clinical characteristics were representative for adult ALL and similar in the cohorts. 766 pts were treated before the amendment with 1000 U/m2 (cohort 1) and 117 pts after the amendment with 2000 U/m2 (cohort 2), with the respective reductions for pts > 55yrs. 76 pts did not receive ASP in induction due to various reasons (cohort 3). Efficacy: In cohort 1 and 2 91% and 90% achieved CR after induction (80% in cohort 3). Data on molecular response, defined as MRD below 10 −4,after induction are available in a subset of both cohorts. There is a trend towards earlier and higher molecular CR rate in cohort 2 (82% after induction) compared to cohort 1 (70%). Survival after 1 yr is similar in cohort 1 (79%) compared to cohort 2 (77%) and inferior in cohort 3 (66%). Probability of continuous CR after 1 year shows a trend to improvement with 87% in cohort 2 vs 77% in cohort 1. Toxicity in induction: Toxicity reported here is focused on potentially ASP related oIII–IV (WHO scale) events. 676 pts are evaluable for cohort 1 and 107 pts for cohort 2. Incidences for both cohorts are as follows: GOT or GPT (30%/27%), bilirubine (12%/14%), thrombosis (5%/2%), bleeding (2%/0%) and hypersensitivity (1%/1%). Details on adverse events of all degrees are available in a subset of pts showing an increase of any WHO grade in 81% for bilirubine, 80% for GPT, 52% for amylase, 29% for lipase and 51% for glucose. Data on substitution of clotting factors were available in 84 and 61 pts: 73% vs 93% required substitution (25%/12% FFP, 37%/46% ATIII concentrate and 37%/42% both). Conclusions: This is the largest cohort of adult ALL pts treated with PEG-ASP so far. Overall intensified PEG-ASP was feasible in the context of intensive multidrug induction. Coagulation disturbances occurred frequently and substitution was extensive, but bleeding or thrombosis were rare events. Although substitution of clotting factors was clinically effective it remains open whether it is clinically necessary. The rate of severe hepatotoxicity was stable after dose escalation however lead to significant treatment delays in individual pts. Lab value changes e.g. liver occured in a large proportion of pts; it remains open to what extent they are clinically relevant and require interruption of further chemotherapy. It would be an important goal to identify parameters to predict severe ASP related toxicities e.g. by pharmacogenomics. The molecular CR rates after dose escalation are promising and will hopefully turn out into an improved overall survival. Supported by supported by Deutsche Krebshilfe 70-2657-Ho2 and partly BMBF 01GI 9971 and Medac GmbH

The geographic distribution of Iris yellow spot virus (IYSV, Genus Tospovirus, Family Bunyaviridae) in onion (Allium cepa L.) crops in the western United States has increased with the most recent report in Colorado (1,4). Furthermore, the incidence of IYSV has increased significantly in onion crops in the Treasure Valley of southern Idaho and eastern Oregon, where the disease was first detected in the United States (1,2). Surveys of onion seed crops in Washington during the past 2 years showed the presence of plants with symptoms characteristic of IYSV infection, including distinct diamond-shaped chlorotic or necrotic lesions, as well as indistinct circular to irregular, chlorotic or necrotic lesions of various sizes on the scapes of flowering plants. To date, symptomatic plants have been observed in five seed crops in Washington, at incidences ranging from <1% to approximately 20% in individual seed crops. Enzyme-linked immunosorbent assays carried out directly on symptomatic onion samples collected in July 2002, and on Nicotiana benthamiana plants mechanically inoculated with sap from these symptomatic plants, did not detect the presence of IYSV. In late July 2003, symptomatic plants were collected from an onion seed crop in Grant County and tested for IYSV infection by reverse transcription-polymerase chain reaction (RT-PCR). Total nucleic acid was extracted from symptomatic areas of the scapes with the procedure described by Presting et al. (3). Primers specific to the nucleocapsid (NP) gene of IYSV were designed based on sequences in GenBank: 5′-TCA GAA ATC GAG AAA CTT-3′ and 5′-TAA TTA TAT CTA TCT TTC TTG G-3′ (sense and antisense polarity, respectively). The RT-PCR assay produced an amplicon of the expected size (approximately 700 bp) that was cloned and sequenced. Comparison with the GenBank IYSV gene sequences showed 98% sequence identity of the NP gene. In August 2003, symptoms of IYSV infection were observed in two onion bulb crops, each located within 2 miles of the symptomatic onion seed crop in Grant County. The presence of IYSV in these crops was confirmed by RT-PCR with cloning and sequencing of the amplicon, as described for the seed crop samples. To our knowledge, this is the first confirmation of IYSV in onion bulb and seed crops in Washington, where 16,000 to 18,000 acres of onion bulb crops and 700 to 900 acres of onion seed crops are grown annually (USDA National Agricultural Statistics Service). The increase in prevalence of IYSV in the Pacific Northwest highlights the need for additional research to clarify the epidemiology of this potentially significant pathogen and to develop a regional management program for iris yellow spot. References: (1) J. M. Hall et al. Plant Dis. 77:952, 1993. (2) J. W. Moyer et al. (Abstr.) Phytopathology 93(suppl.):S115, 2003. (3) G. G. Presting et al. Phytopathology 85:436, 1995. (4) H. F. Schwartz et al. Plant Dis. 86:560, 2002.

Abstract Recently the first cases of lymphoma patients treated with rituximab and combination chemotherapy during pregnancy were reported. We report on a patient with Burkitt’s lymphoma who was treated with rituximab and CHOP therapy early during pregnancy. We were able to monitor rituximab concentrations, B-/T- cell counts and immunoglobulin levels. After delivery these parameters were also measured in the newborn child. A 35-year-old female was diagnosed with CD20+ Burkitt’s lymphoma of the left breast in week 15 of pregnancy. The minimum stage was IIEA; however, the patient also had hepatosplenomegaly. We started treatment with four weekly infusions of rituximab (375mg/m2)(week 16,17,18,19). Treatment was well tolerated with minimal side effects; a minor response was documented by MRI of the breast and ultrasound of previously enlarged axillary lymph nodes. At that time, a decision was made to continue treatment with 6 courses of Cyclophosphamid, Doxorubicin, Vincristin and Prednison (CHOP) at 3 week intervals (week 21, 24, 27, 30, 33, 36). The first 4 courses were preceded by rituximab (375mg/m2). Immunotherapy was tolerated without significant problems. At the end of therapy (week 37) a complete remission was achieved, again documented by MRI and ultrasound. During therapy the child’s growth and intrauterine development were closely monitored by the attending gynecologist. No deviation from normal development were registered. In week 41 of pregnancy the patient delivered a healthy girl (3780g, 55cm, APGAR score 9/10/10) via caesarean section. The girl is now 19 month old, has repeatedly been seen by her pediatrician who reported completely normal growth and developmental status. The mother received high-dose therapy (BEAM) followed by autologous peripheral blood stem cell transplantion 2 months after delivery and has remained in CR with a normal performance status. As the mother has been extremely compliant we were able to repeatedly measure B cell counts, immunoglobulin levels and rituximab concentrations not only in the patient but also in the baby (table 1). Interestingly, at the time of birth very high serum levels of rituximab were measured in the child. Nonetheless a normal B cell recovery was seen during the following weeks, immunological status reached normal values 4 month after delivery and no overt infectious complications have been reported. As to our knowledge, for the first time data of rituximab serum concentrations are available from mother and child. To conclude, in this case combination of immuno- and chemotherapy could be safely administered, achieving a CR in the patient without causing any mental or developmental retardation in the newborn child. In accordance with other reports, this case supports the safety and efficacy of Rituximab administration during pregnancy. Table 1: B/T cell counts and Rituximab concentrations in mother and child during and after treatment with R-CHOP Time Mother Child *values within normal range week of pregnancy/ B-cells T-cells Rituximab B-cells T-cells Rituximab week after delivery CD 19+ CD 3+ CD 19+ CD 3+ cells/μl cells/μl ng/mL cells/μl cells/μl ng/mL 20 0 946 27 0 640 34 4 337 at birth 0 779 9750 0 93 32095 +4 0 759 70 6616* 5399 +18 37 504 <500 1460* 5475* 700

Abstract Oblimersen sodium (Ob, Genasense™) is an 18 mer phosphorothioate antisense directed against bcl-2, an antiapoptotic protein that mediates chemoresistance in malignant cells. In order to assess whether detectable intracellular concentrations (ICs) of Ob are achievable in vivo, we have developed a sensitive and specific ELISA-based assay. This assay involves Ob hybridization to a 5′-end overhang of a 3′-biotinylated capture probe ligated to a digoxigenin (Dig)-labeled probe, and detection by an anti-Dig-alkaline phosphatase system. In K562 cell extract, the assay was linear within 50–2000 pM range with a limit of quantification (LOQ) of 50 pM (equivalent to 5.0 fmol/100 μL). The withtin-run coefficients of variation (CVs) in 4 spiked concentrations were between 3–7% in 6 replicates with accuracy values between 93–109%. The between-run CVs were between 6–12% and accuracy values between 97–102%. The specificity of the assay was demonstrated by low cross reactivity with mismatched oligonucleotides and putative 3′-end metabolites shortened by 1, 2 or 3 nucleotides. Validation of IC measurement was performed in vitro in K562 cells treated with fluorescent labeled Ob conjugated to oligofectamine. At Ob concentrations between 0.1 – 10 μM, Bcl-2 mRNA downregulation measured by real-time RT-PCR occurred efficiently. Nonlinear regression analysis of a dose-response curve showed that 50% Bcl-2 downregulation (IC50) occurred at approximately 0.29 μM, corresponding to an Ob IC concentration of 37 pmole/mg protein. Cellular uptake was confirmed by microscopy and flow cytometry. To validate these results in vivo, we measured Ob IC in bone marrow samples from untreated AML pts aged > 60 yrs enrolled on the phase I study OSU 0164. These pts were induced with Ob 7 mg/kg/d CIVI on days 1–10, cytarabine 100 mg/m2/d CIVI on days 4–10 and daunorubicin administered iv at two dose levels (45 mg/m2/d IV and 60 mg/m2/d) on days 4–6. Among 21 pts assessable for clinical response and Bcl-2 levels, at pretreatment, Bcl-2 copy numbers (normalized to ABL) were higher among 12 pts who achieved a CR (median 85,325; range 19,120–149,100) than among 9 non-responsive (NR) pts (32,100 bcl-2 /abl copies; range 1,488–163,500) (P=.04; Mann-Whitney test). Following 72 hr Ob infusion, a decrease (−38%) in median Bcl-2/ABL mRNA copies in CR patients and an increase (+115%) in Bcl-2/ABL copies in NR pts (P=.002; Mann-Whitney test) were observed by real time RT-PCR. A trend in higher median IC of Ob was observed in CR pts (17.0 pmole/mg protein; range 1.5–30.0) as compared to NR pts (4.4 pmole/mg protein; range 0.33–28.0) (P=.06; Mann-Whitney test). Six of 7 pts with IC above the median obtained a CR. No differences were observed in the Ob plasma PKs between the CR pts [median steady state concentration (Css) 2.8 μg/mL, area-under-the-curve (AUC) 772 μg*hr/mL and clearance (Cl) 9.6 L/hr) and the NR pts (median Css 3.4 μg/mL, AUC 752 μg*hr/mL, Cl 6.4 L/hr). Although the number of samples analyzed was small, our data suggest that, despite interpatient variability of both Bcl-2 mRNA expression and Ob uptake, this antisense can be successfully delivered to pts and result in clinically relevant target downregulation. A Cancer and Leukemia Group B phase III AML study to characterize prospectively the interplay of IC levels of the Ob and Bcl-2 downregulation is in progress.

Abstract Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal bone marrow disorder caused by a somatic mutation in PIGA that leads to a marked deficiency or absence of the complement regulatory proteins CD55 and CD59. The disease manifests with intravascular hemolysis, anemia and thrombosis. PNH is characterized by diverse changes in iron metabolism. Chronic hemolysis leads to the massive iron loss due to hemoglobinuria and hemosiderinuria, whereas frequent transfusions in severely anemic, transfusion-dependent patients might cause the development of iron overload. A im: to assess iron metabolism in PNH patients based on both laboratory parameters and MRI data. Methods: the study group included 28 PNH patients (pts) followed up in our Center between 2015 and 2017. Laboratory parameters including hemoglobin (Hb), reticulocytes (RET), erythrocyte and granulocyte PNH clone sizes and LDH levels were analyzed. Iron metabolism was characterized by measurement of serum ferritin (SF), transferrin, iron concentration, total iron binding capacity (TIBC), transferrin saturation (TS). Multiecho gradient-echo T2* magnetic resonance imaging (T2* MRI) was performed to assess both liver and kidney iron load. All pts were divided into 3 cohorts: №1 - pts on treatment with eculizumab, №2 - pts who received eculizumab in the past and №3 - eculizumab naïve pts. Results: Сohort №1 included 2 pts (2 women) aged 39 and 64 yrs. Hb level was 9,3 and 9,9 g/dl, RET count - 9,6 and 10%, LDH level - 570 and 650 U/l. Erythrocyte PNH clone size was 99 and 72%, and granulocyte PNH clone size was 99 and 87%. Cohort №2 consisted of 6 pts (2 men and 4 women, median age 39 yrs (31 - 53)) which had a history of eculizumab treatment. The median duration of eculizumab treatment in these pts was 23 months, the median time of treatment cessation (due to administrative reasons) was 6 months before study assessments. The medians of laboratory parameters were as follows: Hb = 7,7 g/dl, RET count = 6,6%, LDH level = 3296 U/l (1580 - 7444), erythrocyte PNH clone size = 36%, granulocyte PNH clone size = 98%. Cohort №3 consisted of 20 untreated pts (15 men and 5 women, median age 35 yrs (29 - 58)). The medians of laboratory parameters: Hb = 8,4 g/dl, RET count = 8,5%, LDH level = 4130 U/l (670 - 8322), erythrocyte PNH clone size = 52%, granulocyte PNH clone size = 93%. Serum iron metabolism indices in all patient cohorts are reported in Table 1. Based on the analysis of the measured serum iron metabolism indices, 3 types of iron metabolism disturbances were identified in pts of the study group (n=28): iron deficiency (14% of pts), iron overload (21% of pts) and divergent changes (65% of pts). T2* MRI was performed in 23 pts. Signs of liver iron overload were revealed in 35% pts whereas signs of kidney iron overload were detected in 91% pts. T2* MRI data was analyzed within each of the patient cohorts, results are reported in Table 1. Conclusion: the results of our pilot study demonstrate that in PNH patients laboratory parameters are not sufficient to assess iron metabolism. T2* MRI is a noninvasive and accurate technique which should be considered as a method of choice to quantify tissue iron overload. Kidney iron overload was detected in all PNH patients who did not receive eculizumab at the moment of the analysis and was absent in 2 patients on eculizumab. Thus, hemosiderin deposition in the renal cortex might play an important role in the development of renal involvement including the formation of interstitial fibrosis and chronic kidney disease. Disclosures Lukina: Sanofi Genzyme: Honoraria, Other: Principal investigator in the eliglustat Phase 2, ENGAGE, ENCORE, and EDGE trials; receives travel reimbursement; member of advisory boards, Research Funding.

Abstract Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of conditioning for hematopoietic stem cell transplant (HSCT). Severe VOD/SOS (ie, with multi-organ dysfunction [MOD]) may be associated with >80% mortality. Defibrotide is approved for treatment of severe VOD/SOS in the EU. In the US, defibrotide is available through an ongoing, expanded-access study. The optimal time to initiate VOD/SOS treatment with defibrotide is of interest. Methods In the expanded-access study, patients were eligible in the original protocol if they had VOD/SOS and renal/pulmonary MOD by Baltimore criteria post-HSCT or by biopsy. The protocol was amended to include (1) post-chemotherapy patients, (2) patients without MOD, and (3) VOD/SOS per modified Seattle criteria. Defibrotide 25 mg/kg/day was given in 4 divided doses for a recommended ≥21 days. Here, Day +100 survival in patients with HSCT was examined post hoc based on time from VOD/SOS diagnosis (with or without MOD as relevant to study entry criterion) to initiation of defibrotide. Two analyses were conducted: (1) survival rate analyzed by treatment initiation for the entire population before or after each of the following days: 1, 2, 3, 4, 7, and 14, using Fisher's exact test; (2) survival rate for only those patients with treatment initiated on a particular day: 0, 1, 2, 3, 4, 5, 6, 7, 8-14, and ≥15, with a Cochran-Armitage test for trend across days. Results Among HSCT patients enrolled through 2013 who received ≥1 dose of defibrotide, treatment date was available for 573 patients. Of these, 351 also had MOD. Defibrotide was started on the day of diagnosis in >30% of patients; >90% of patients started defibrotide before day 7 post-diagnosis. In the population-wide analysis of treatment initiation before or after days 1, 2, 3, 4, 7, and 14, earlier initiation of defibrotide was associated with higher survival rates (Table), and was statistically significant for all cut-points considered except 14 days, with only 2.8% of patients beginning treatment post-day 14. Survival differences between earlier vs. later initiation ranged from 8.8% to 22.1% overall (MOD: 12.8% to 25.6%; Table) for the cut-points considered. In the analysis of relationship between Day +100 survival and treatment initiation day, survival rates were generally higher if treatment was initiated earlier. This was demonstrated by a statistically significant trend over time for better outcomes with earlier initiation (Figure). Similar results for both analyses were obtained for all patients with VOD/SOS and for the subgroup of patients with MOD. Conclusions Data indicate decreased Day +100 survival associated with longer treatment delays, confirmed by the Cochran Armitage trend test (P<0.001). Thus, defibrotide treatment should be initiated as soon as possible after VOD/SOS diagnosis. Table. Day +100 Survival by Defibrotide Initiation Day n (%) HSCT VOD/SOS (N=573) HSCT VOD/SOS with MOD (n=351) Initiation Period Alive Dead Unknown Alive Dead Unknown ≤1 Day 183 (53.5) 142 (41.5) 17 (5.0) 103 (50.2) 93 (45.4) 9 (4.4) >1 Day 105 (45.5) 116 (50.2) 10 (4.3) 56 (38.4) 85 (58.2) 5 (3.4) Difference (95% CI)a 8.8% (0.2%, 17.3%) 12.8% (2.0%, 23.4%) P valueb 0.045 0.021 ≤2 Days 235 (55.7) 166 (39.3) 21 (5.0) 132 (52.2) 111 (43.9) 10 (4.0) >2 Days 53 (35.1) 92 (60.9) 6 (4.0) 27 (27.6) 67 (68.4) 4 (4.1) Difference (95% CI)a 22.1% (12.6%, 31.2%) 25.6% (13.8%, 36.9%) P valueb <.001 <.001 ≤3 Days 251 (53.5) 193 (41.2) 25 (5.3) 138 (49.5) 129 (46.2) 12 (4.3) >3 Days 37 (35.6) 65 (62.5) 2 (1.9) 21 (29.2) 49 (68.1) 2 (2.8) Difference (95% CI)a 20.3% (9.6%, 30.8%) 21.7% (8.6%, 34.5%) P valueb <.001 0.001 ≤4 Day 263 (52.6) 212 (42.4) 25 (5.0) 146 (48.7) 142 (47.3) 12 (4.0) >4 Day 25 (34.2) 46 (63.0) 2 (2.7) 13 (25.5) 36 (70.6) 2 (3.9) Difference (95% CI)a 20.2% (7.7%, 32.4%) 24.2% (9.1%, 38.9%) P valueb 0.002 0.002 ≤7 Days 275 (51.6) 232 (43.5) 26 (4.9) 152 (47.4) 156 (48.6) 13 (4.0) >7 Days 13 (32.5) 26 (65.0) 1 (2.5) 7 (23.3) 22 (73.3) 1 (3.3) Difference (95% CI)a 20.9% (4.5%, 37.1%) 25.2% (6.1%, 43.8%) P valueb 0.013 0.011 ≤14 Days 282 (50.6) 249 (44.7) 26 (4.7) 156 (45.9) 171 (50.3) 13 (3.8) >14 Days 6 (37.5) 9 (56.3) 1 (6.3) 3 (27.3) 7 (63.6) 1 (9.1) Difference (95% CI)a 13.1% (-12.9%, 39.5%) 17.7% (-14.6%, 51.5%) P valueb 0.433 0.344 aAlive and Dead. 95% CI calculated using exact method. bFisher's exact test, Alive and Dead. Support: Jazz Pharmaceuticals. Disclosures Richardson: Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Kernan:Gentium S.p.A.: Research Funding. Grupp:Novartis: Consultancy, Research Funding. Antin:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Miloslavsky:Jazz Pharmaceuticals: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals: Employment, Equity Ownership. Hannah:Jazz Pharmaceuticals: Consultancy. Nejadnik:Jazz Pharmaceuticals: Employment, Equity Ownership. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: The EUMDS registry collects prospective observational data on lower-risk MDS patients from 142 centers in 17 countries. Red blood cell (RBC) transfusions remain one of the cornerstones in supportive care. Patients are prone to iron overload due to long-term iron accumulation either caused by RBC transfusions or ineffective erythropoiesis and associated iron toxicity through the formation of toxic iron species. Methods: We analyzed serum from 100 lower-risk MDS patients at six-month intervals for ferritin, transferrin saturation (TSAT), hepcidin-25, and toxic iron species (non-transferrin bound iron (NTBI) and labile plasma iron (LPI)) in order to evaluate temporal changes in iron metabolism and presence of potentially toxic forms of ironand their impact on survival. Results: Themedian age was 73 years (range 44-95 years). WHO2001 MDS-subtypes were RCMD (37%), RARS (30%), RA (18%), RAEB (7%), 5q-syndrome (4%) and RCMD-RS (4%). The table shows iron parameters at registration, 1 and 2 years follow-up both in transfusion-dependent (TD) and transfusion-independent (TI) patients and according to: MDS-RS (RARS/RCMD-RS) or MDS Other (RA/RCMD/RAEB/5q-syndrome). Serum ferritin levelswere increased in TD patients, compared to TI patients. Ferritin correlated significantly with hepcidin-25 (r=0.57, p<0.001) as well as CRP (r=0.27, p<0.001). Hepcidin-25 levelswere elevated in TD patients at registration and remained elevated during follow-up (Table 1). Hepcidin levels were low in MDS-RS TI patients at all time points compared to nonRS MDS patients (Table 1). NTBI levelswere elevated in TD patients compared to TI patients at registration and during follow-up. Also TI MDS-RS patients had NTBI levels above the lower limit of detection (LLOD; 0.47 µmol/L). NTBI levels over time were highest in TD MDS-RS patients. LPI levelswere mainly increased above LLOD (0.21 µmol/L) in patients with high TSAT levels (>80%). Both NTBI and LPI had a stronger association with TSAT (Figure 1AC) compared to ferritin (Figure 1BD). Elevated LPI levels in combination with high TSAT levels (>80%) occurred almost exclusively in patients with MDS-RS and/or previous transfusions (Figure 1AC). Cox regression analysis for overall survival was adjusted for age at diagnosis, cumulative number of transfused units and TSAT, NTBI or LPI respectively as a time varying covariate. LPI showed a negative impact on overall survival (HR 1.97; 95%CI 0.39-9.92), independent of transfusion status (Figure 2), while NTBI and TSAT did not show relevant impact on overall survival (HR 1.04; 95% 0.91-1.20; HR 1.00; 95%CI 0.99-1.02, respectively). Conclusion: This is the first clinical outcome study which illustrates LPI as a clinically relevant assay format for identification of the toxic fraction of overt iron overload and its negative impact on overall survival. Table 1. Ferritin, Hepcidin-25, NTBI, LPI during follow-up Iron parameter Registration 1 yr follow-up 2 yrs follow-up N Median (p25-p75) N Median (p25-p75) N Median (p25-p75) Ferritin (µg/L)MDS Other: TI MDS Other: TD MDS-RS: TI MDS-RS: TD 94 51 13 26 4 274.0 (131.0 - 546.0) 188.0 (81.2 - 375.0) 408.0 (272.0 - 665.0) 271.5 (160.0 - 580.0) 947.5 (359.0 - 1333.5) 82 34 22 20 6 290.5 (149.0 - 845.0) 164.5 (78.3 - 293.0) 837.0 (550.0 - 1538.0) 257.0 (189.5 - 557.5) 1354.0 (859.0 - 2217.0) 64 28 15 11 10 346.5 (185.5 - 723.5) 204.5 (86.5 - 346.5) 642.0 (264.0 - 1970.0) 357.0 (222.0 - 597.0) 846.0 (590.0 - 1922.0) Hepcidin (nmol/L) MDS Other: TI MDS Other: TD MDS-RS: TI MDS-RS: TD 93 51 13 25 4 4.5 (2.7 - 8.4) 4.4 (2.7 - 8.3) 9.6 (4.5 - 26.3) 3.5 (1.5 - 4.9) 10.4 (7.9 - 13.5) 82 34 22 20 6 5.7 (2.7 - 12.7) 5.0 (2.3 - 8.1) 17.4 (10.2 - 23.7) 3.6 (1.7 - 5.0) 9.4 (8.8 - 14.4) 64 28 15 11 10 5.1 (2.5 - 8.9) 4.6 (2.5 - 7.1) 8.1 (2.4 - 12.8) 2.9 (1.3 - 6.1) 5.3 (2.9 - 9.3) NTBI (µmol/L) 0 RBC units <=10 RBC units >10 RBC units 91 78 12 1 0.65 (0.31 - 1.14) 0.58 (0.30 - 1.13) 0.94 (0.40 - 3.12) 0.81 (0.81 - 0.81) 76 52 12 12 0.57 (0.20 - 1.43) 0.53 (0.19 - 0.84) 0.58 (0.16 - 1.32) 2.97 (0.50 - 3.77) 60 39 14 7 0.62 (0.33 - 2.27) 0.52 (0.33 - 1.05) 1.64 (0.39 - 2.27) 3.31 (1.35 - 7.25) LPI (µmol/L) 0 RBC units <=10 RBC units >10 RBC units 91 78 12 1 0.13 (0.06 - 0.18) 0.13 (0.06 - 0.18) 0.13 (0.04 - 0.18) 0.13 (0.13 - 0.13) 76 52 12 12 0.12 (0.05 - 0.18) 0.11 (0.04 - 0.16) 0.07 (0.04 - 0.18) 0.20 (0.15 - 0.34) 60 39 14 7 0.10 (0.06 - 0.17) 0.10 (0.06 - 0.16) 0.11 (0.08 - 0.16) 0.18 (0.04 - 1.08) Figure 2. Impact of LPI on survival stratified by transfusion status (landmark analysis) Figure 2. Impact of LPI on survival stratified by transfusion status (landmark analysis) Disclosures de Witte: Novartis: Research Funding.

Abstract Abstract 823 The new WHO classification of AML first considers genetic and molecular findings, the history of the patient but also stresses the importance of multilineage dysplasia (MLD) as independent parameter: Cases not classified as AML with recurrent genetic abnormalities or therapy-related AML are classified as AML with myelodysplasia-related changes (MRC) with one of the following parameters: AML after MDS or MDS/MPN (s-AML), AML with MDS-related cytogenetics and/or AML with MLD. All other cases are classified “AML, not otherwise specified” (NOS). We analyzed 1740 AML, 12.5% were AML with recurrent cytogenetic abnormalities, 7.4% were t-AML. We then evaluated a subgroup of 461 pts with AML without recurrent cytogenetic abnormalities. All of them were included based on complete availability of clinical data, cytogenetic and molecular features and adequate material for morphologic assessment. After morphologic analysis another 53 cases had to be excluded as dysplastic features were not evaluable following WHO guidelines. Following the WHO proposal cases of the provisional entities “AML with mutated NPM1” and “AML with mutated CEBPA” have not been excluded. We investigated dysplasia in all cases (n= 408) and found 184 AML with MRC (45.1%) and 224 AML NOS (54.9%). In 93/184 (50.5%) cases MLD alone led to the classification as AML with MRC. Out of the remaining 91 cases 42 had AML arising from previous MDS or MDS/MPN and 55 had AML with an MDS-related cytogenetic abnormality (both parameters present in 5 cases). Event-free survival (EFS) and overall survival were comparable in AML with and without MLD (median EFS 13.8 vs. 15.2 months, n.s.; median OS 24.5 vs. not reached, n.s.). MLD was positively correlated to the incidence of pre-existing MDS or MDS/MPN (frequency in cases with pre-existing MDS or MDS/MPN vs. others 66.7% vs. 33.1%, p<0.0001) and to MDS-related cytogenetic abnormalities (frequency in cases with MDS-related cytogenetic abnormalities vs. others 54.5% vs. 33.7%, p= 0.004). Thus, to analyze whether or not MLD as a sole criterion has clinical impact the following evaluations focused on the subgroup AML MLD sole (AML with MLD and without other MRC in comparison to AML NOS regarding clinical and prognostic parameters including age, WBC, cytogenetics, molecular markers, OS and EFS. Median age was 61.7 vs. 66.0 years in AML MLD vs. AML NOS (range 20.4-85.0 vs. 18.3-88.1 years, p=0.027) and the median WBC count was 18.3 vs. 13.4 G/l (range 0.4-370.0 vs. 0.14-600.0 G/L, n.s.). Pts with AML MLD exhibited a slightly lower frequency of NPM1 mutations (58.0% vs. 64.7%, n.s.) and a lower frequency of FLT3-ITD (18.0% vs. 28.5%, p= 0.061), and showed slightly more frequently NRAS mutations (18.2% vs. 9.6%, n.s.). Frequencies of MLL-PTD and CEBPA-mutations were similar between both groups. In the subgroup AML MLD sole (AML with MLD and without other MRC) in comparison to AML NOS, the presence of MLD has no impact on EFS (median 17.5 vs. 16.0 months, n.s.) and OS (3-year-OS 54.8% vs. 53.9%, n.s.). Further analyses were performed for the total cohort (n=408). MDS-related cytogenetics was associated with shorter EFS (median 7.2 vs. 15.2 months, p=0.011) and OS (median 17.4 months vs. not reached, p=0.010). Also, s-AML was associated with shorter EFS (12.7 vs. 15.6 months, p=0.099) and OS (15.0 months vs. not reached, p=0.027). Furthermore we assessed the prognosis of pts with AML NOS combined with the subgroup of AML MRC showing MLD only (n= 317) vs. all other cases with AML MRC being assigned to this group based on cytogenetics or preceding MDS/MPN (n= 91). A significant difference in OS (AML NOS and AML MLD only vs. AML MRC based on cytogenetics or preceding MDS/MPN, median OS not reached vs. 15.8 months, p= 0.001) and EFS (median 16.8 vs. 10.2 months, p= 0.004) was seen. Among the other prognostic parameters, only absence of NPM1 mutation, presence of MLL-PTD and higher age were significantly associated with a worse EFS and OS. In multivariate analysis a higher age was the only parameter independently related to worse EFS (p<0.0001), and higher age (p<0.0001) and MLL-PTD (p=0.033) were the only parameters independently related to shorter OS. These facts lead to the conclusion that MLD alone has very limited clinical impact and that pts with MLD and without previous MDS or MDS/MPN or MDS-related cytogenetic abnormalities should not be classified only by morphology as AML MRC. We suggest that classification of pts with AML could be simplified by only using cytogenetics and prior history for a reproducible risk-stratification in the setting of clinical trials. Disclosures: Miesner: MLL Munich Leukemia Laboratory: Employment. Weiss:MLL Munich Leukemia Laboratory: Employment. Macijewski:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

Управление скоростью формирования и характеристиками наноразмерных пленок на InP целесообразно осуществлять введением в процессе термооксидирования этого полупроводника хемостимуляторов, модификаторов, или и тех, и других одновременно. Хемостимулирующее действие соединений обусловлено их транзитной ролью как передатчиков кислорода или каталитической функцией. Модификаторы могут, не изменяя скорости роста пленки, влиять на ее состав, морфологию поверхности, структуру и свойства. Предполагается продуктивным воздействие хемостимуляторов и модификаторов в едином процессе синтеза пленок с заданными свойствами.Цель статьи – установление воздействия некоторых сложных хемостимуляторов и модификаторов на кинетику, механизм роста и свойства сложнооксидных пленок нанометрового диапазона толщины на InP.Объект исследования – фосфид индия ФИЭ-1А ориентации (100). Методом магнетронного напыления сформированы гетероструктуры (ГС): SnO2/InP и (40 % Co3O4+60 % MnO2)/InP с толщиной слоя ~30 нм. Для формирования ГС Bi2(SO4)3/InP проводили осаждение сульфата через аэрозольную фазу с последующим высушиванием на воздухе и отжигом в режиме 200 °С, 30 мин. Образцы SnO2/InP и InP термооксидировали под воздействием вводимых в газовую фазу AlPO4 и Bi2(SO4)3 соответственно в температурном интервале 490-570 °С в потоке кислорода в течение 60 минут.Толщину пленок контролировали методами лазерной и спектральной эллипсометрии, их фазовый и элементный состав методами РФА и Оже-электронной спектроскопии соответственно. Для определения электрофизических свойств плёнок напыляли алюминиевые контакты и определяли удельное сопротивление. Установлена основополагающая роль физико-химической природы хемостимулятора, его способности к транзитному взаимодействию и возобновляемости оксидных форм в процессе термооксидирования InP. Введение в термические оксидные пленки фосфатных группировок из AlPO4, совместно с нанесением на поверхность SnO2 или без этогоприводит к сопротивлению пленок, аналогичному таковому для оксидирования ГС SnO2/InP, без дополнительного введения фосфатов и составляет 8.5·107 Ом·см. Bi2(SO4)3, являясь модификатором состава и свойств пленок, не оказывает значимого хемостимулирующего действия. Выращенные под его воздействием пленки обладают полупроводниковым характером (r ~ 106 Ом·см). Наиболее эффективен сложный хемостимулятор состава 40 % Co3O4+60 % MnO2, обусловливающий ускоренное (до 70 %) по сравнению с собственным оксидированием формирование пленок по транзитно-каталитическому механизму, входящий в состав синтезированных пленок и способный кцеленаправленной модификации их свойств варьированием содержания компонентов в нем (РФА, СЭ).
 
 
 
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The debate about diagnoses and treatment of attention deficit hyperactive disorder (ADHD) in children continue to range on between the developmental and biological perspectives. While there is increasing evidence that support the biological susceptibility of the disorder, a number of researches also emphasized the significant effect of environment on the syndrome. This study used developmental perspectives to evaluate and bring together various bio-psychosocial factors that impact on children diagnosed with ADHD. The study explored and integrated the existing and advancing study on ADHD to a more refined pattern that embraced developmental perspectives. The study also discussed how the linkage in childhood ADHD fits within the developmental psychopathology perspective. The study revealed that ADHD as a developmental disorder is influenced by prenatal, biological and psychosocial environmental risk factors, and suggested that better understanding of genomic susceptibilities, family environment and parental characteristics would transform the pathway for development of ADHD in children.
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Abstract Background Cardiac disease occurs more frequently in obesity patients. Imaging by transthoracic echocardiography (TTE) can be limited due to poor acoustic windows. An increase of the number of obesity patients who need to undergo TTE is expected. Purpose The aim of this study was to evaluate the feasibility, test-retest variability and inter- and intra-observer variability of parameters of cardiac function and dimension by TTE in obesity patients as compared to non-obese controls. Methods 100 obesity patients (BMI≥35kg/m2) and 50 non-obese controls (BMI < 30kg/m2) without known cardiovascular disease were prospectively enrolled and underwent an echocardiogram. Feasibility of echocardiographic parameters was assessed by categorizing the image quality and by evaluating the availability of the echocardiographic parameters. Intra-observer reproducibility was assessed by one observer on the same echocardiographic loop in 50 patients. A second observer assessed interobserver reproducibility in these patients. In 37 obesity patients and 17 non-obese controls images were obtained by two physicians to investigate test-retest variability. Results Image quality was excellent in 11% of the obesity patients as compared to 60% of the non-obese controls. Nevertheless, apart from global longitudinal strain (GLS), all investigated parameters of cardiac function and dimension were available in both groups (Table). GLS was obtainable in 93% of obesity patients versus 98% of non-obese controls (p = 0.20). For the vast majority of parameters inter- and intra-observer variability was comparable between obesity patients and non-obese controls. There were no significant differences between obesity patients and non-obese controls regarding the test-retest variability (Table). Conclusion Although non-obese controls on average had better echocardiographic image quality than obesity patients, feasibility of assessment of a broad variety of parameters of cardiac function and dimension was excellent in obesity patients and there were no important differences regarding variability of measurements. Echocardiographic parameters Available obesity patients (n = 100) Available non-obese controls (n-50) Intra-observer variability obese (n = 50) Intra-observer variability non-obese (n = 25) Inter-observer variability obese (n = 50) Interobeserver variability non-obese (n = 25) Test-retest variability obese (n = 37) Test-rest variability non-obese(n= 17) IVSd 100% 100% 10.6 ± 6.3 6.8 ± 6.3* 10.8 ± 6.9 8.5 ± 4.5 11.1 ± 9.0 10.1 ± 6.4 LVEDD 100% 100% 5.4 ± 4.7 6.7 ± 5.3 5.5 ± 3.7 5.5 ± 3.3 6.7 ± 5.1 6.1 ± 5.2 PWd 100% 100% 12.4 ± 9.0 13.7 ± 9.6 11.5 ± 9.7 9.7 ± 6.7 12.4 ± 9.4 9.8 ± 6.4 E/A ratio 100% 100% 5.9 ± 9.6 2.1 ± 3.0 4.9 ± 5.0 3.8 ± 3.4 8.9 ± 5.7 8.5 ± 5.7 LA-volume index 100% 100% 12.3 ± 7.8 8.7 ± 6.5 11.0 ± 6.9 9.2 ± 4.8 13.6 ± 11.8 10.1 ± 6.3 GLS 93% 98% 6.8 ± 5.2 5.6 ± 4.6 6.4 ± 4.9 5.6 ± 4.6 8.8 ± 7.6 6.9 ± 5.3 Selection of various echocardiographic parameters. *p < 0.05

Abstract Objectives A significant proportion of RA patients, particularly those associated with poor prognostic factors, fail on conventional DMARDs (cDMARDs). Although rituximab (RTX) has been effective in these patients, the cost of therapy makes it unaffordable, particularly in poor and developing countries. Numerous, albeit small, studies using lower doses have shown contradictory results. We aimed to analyse the effectiveness of a low-dose RTX protocol based on clinical outcomes in RA patients. Methods Seropositive RA patients with moderate to high disease activity (DAS28-ESR > 3.2) despite combination cDMARDs, treated with RTX, were included in retrospective analysis. All patients were treated according to a predefined protocol, using 500 mg RTX with ongoing cDMARDs at baseline and repeat dosing at 6 weeks or beyond, on lack of moderate to good EULAR response. The B cell count was assessed at baseline, 2 and 24 weeks. Results At 12 weeks, 93% of 166 patients [mean (s.d.) age, 51.5 (11.96) years, 25 men and 141 women, with a disease duration of 10.4 (6.29) years] achieved moderate to good EULAR response. At 24 weeks, 90.8% of patients achieved moderate to good EULAR response, 19.8% achieved low disease activity and 29.5% achieved remission, with a mean change in DAS28-ESR from baseline of 2.9 (1.3). RTX failure and relapse were seen in 5.4% and 3.6%, respectively. The response was maintained for 12.3 (7.2) months with a mean RTX dose 521.1 (100.8) mg. Adverse events were seen in 9.6%. When compared with the standard dosing regimen with the originator molecule, a cost reduction of 90% was achieved. Conclusion A low-dose RTX regimen achieved reasonably good clinical outcomes at the end of 6 months, with a significantly lower cost.

The volume of glaciers in Iceland (∼3,400 km3 in 2019) corresponds to about 9 mm of potential global sea level rise. In this study, observations from 98.7% of glacier covered areas in Iceland (in 2019) are used to construct a record of mass change of Icelandic glaciers since the end of the 19th century i.e. the end of the Little Ice Age (LIA) in Iceland. Glaciological (in situ) mass-balance measurements have been conducted on Vatnajökull, Langjökull, and Hofsjökull since the glaciological years 1991/92, 1996/97, and 1987/88, respectively. Geodetic mass balance for multiple glaciers and many periods has been estimated from reconstructed surface maps, published maps, aerial photographs, declassified spy satellite images, modern satellite stereo imagery, and airborne lidar. To estimate the maximum glacier volume at the end of the LIA, a volume–area scaling method is used based on the observed area and volume from the three largest ice caps (over 90% of total ice mass) at 5–7 different times each, in total 19 points. The combined record shows a total mass change of −540 ± 130 Gt (−4.2 ± 1.0 Gt a−1 on average) during the study period (1890/91 to 2018/19). This mass loss corresponds to 1.50 ± 0.36 mm sea level equivalent or 16 ± 4% of mass stored in Icelandic glaciers around 1890. Almost half of the total mass change occurred in 1994/95 to 2018/19, or −240 ± 20 Gt (−9.6 ± 0.8 Gt a−1 on average), with most rapid loss in 1994/95 to 2009/10 (mass change rate −11.6 ± 0.8 Gt a−1). During the relatively warm period 1930/31–1949/50, mass loss rates were probably close to those observed since 1994, and in the colder period 1980/81–1993/94, the glaciers gained mass at a rate of 1.5 ± 1.0 Gt a−1. For other periods of this study, the glaciers were either close to equilibrium or experienced mild loss rates. For the periods of AR6 IPCC, the mass change rates are −3.1 ± 1.1 Gt a−1 for 1900/01–1989/90, −4.3 ± 1.0 Gt a−1 for 1970/71–2017/18, −8.3 ± 0.8 Gt a−1 for 1992/93–2017/18, and −7.6 ± 0.8 Gt a−1 for 2005/06–2017/18.

Doenças cardíacas, congênitas ou adquiridas, representam grande parte da casuística do atendimento de cães. Estima-se que aproximadamente 10% dos atendimentos iniciais em cães ocorrem devido a doença cardíaca, e a doença mixomatosa valvar mitral (DMVM) corresponde à maioria das cardiopatias nessa espécie (Keene et al., 2019). A ecocardiografia é um exame complementar não invasivo, importante para o diagnóstico das cardiopatias. Assim, o objetivo deste estudo foi analisar a prevalência de cães cardiopatas diagnosticados por meio da ecocardiografia, atendidos pelo Laboratório de Cardiologia Comparada do Hospital Veterinário da UFPR, durante o período de 2015 a 2019. Foram descartados da amostra os pacientes com diagnósticos incompletos, e apenas o exame mais recente do mesmo animal foi considerado. Sendo assim, foram analisados 2703 cães, dos quais 1668 possuíam pelo menos uma cardiopatia. Dentre os cardiopatas, 953/1668 eram fêmeas (57,1%) e 715/1668 eram machos (42,9%). Cães sem raça definida foram os mais acometidos 552/1668 (33,1%), seguidos das raças Poodle 235/1668 (14,1%), Lhasa Apso 123/1668 (7,4%), Pinscher 103/1668 (6,2%), Dachshund 95/1668 (5,7%) e demais raças 560/1668 (33,6%). A maioria dos animais 1580/1668 (94,7%) foi diagnosticada com cardiopatias adquiridas. Destes, 40/1580 (2,5%) apresentavam idade entre dois e cinco anos, 548/1580 (34,7%) entre seis e dez anos, 841/1580 (52,3%) entre 11 e 15 anos, 93/1580 (5,9%) acima de 15 anos e 58/1580 (3,7%) não tiveram suas idades informadas. Os outros 88/1668 (5,3%) cães apresentaram doenças congênitas, destes 21/88 (23,9%) apresentavam menos de um ano de idade, 11/88 (12,5%) entre dois e cinco anos, 32/88 (36,4%) entre seis e dez anos, 21/88 (23,9%) entre 11 e 15 anos, 1/88 (1,1%) acima de 15 anos e 2/88 (2,3%) não tiveram as idades informadas. A DMVM foi a cardiopatia mais diagnosticada, observada em 1560/1668 (93,5%) cães. A segunda maior afecção foi a degeneração mixomatosa da valva tricúspide (DMVT), observada em 756/1668 (45,3%) cães. O terceiro diagnóstico mais comum foi a cardiomiopatia dilatada acometendo 39/1668 (2,3%) animais, seguido por neoplasias cardíacas observadas em 20/1668 (1,2%) cães. As demais doenças tiveram menor prevalência, afetando dez indivíduos ou menos, sendo elas: estenose aórtica, comunicação interatrial, estenose pulmonar, displasia de mitral, displasia de tricúspide, endocardite, cor pulmonale, comunicação interventricular, persistência do ducto arterioso, estenose subaórtica, estenose mitral, persistência da veia cava cranial esquerda, hérnia diafragmática peritoneopericárdica, dirofilariose, degeneração aórtica, coronária anômala, cardiomiopatia arritmogênica, aneurisma, tromboembolismo pulmonar, trombo em átrio direito, tetralogia de Fallot, miocardite, cor triatriatum sinister e calcificação aórtica, respectivamente. Ao todo, 907/1668 (54,4%) animais apresentaram apenas uma doença cardíaca, 737/1668 (44,2%) apresentaram duas doenças concomitantes, e 24/1668 (1,4%) apresentaram três ou mais doenças conjuntas. O estudo de prevalência das cardiopatias auxilia na elaboração de diagnósticos diferenciais e, portanto, na escolha do plano terapêutico.

Penelitian ini bertujuan untuk mengetahui Peran Mediasi Komitmen Organisasional pada Pengaruh Big Five Personality dan Persepsi Dukungan Organisasi Terhadap Organizational Citizenship Behavior. Metode penelitian yang digunakan dalam penelitian ini adalah menggunakan metode deskriptif kuantitatif. Sampel yang digunakan dalam penelitian ini yakni perawat dan bidan pada RSUD Sultan Syarif Mohamad Alkadrie. Data diperoleh dari kuesioner yang kemudian diolah dan dianalisis dengan menggunakan analiais jalur melalui Doftware SPSS 17.00.Hasil penelitian menunjukkan bahwa Big FivePersonality dan Persepsi Dukungan Organisasi berpengaruh signifikan terhadap Komitmen Organisasional. Sementara itu Big Five Personality dan Persepsi Dukungan Organisasi juga berpengaruh langsung terhadap Organizational Citizenship Behavior. Sementara itu, Komitmen Organisasional berpengaruh terhadap Organizational Citizenship Behavior. 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