Journal articles on the topic '004.4:519.816 (043.3)'

AbstractBackgroundThe sensitivity of blood cultures increases with the volume of blood collected. However, hospitals face challenges in collecting adequate volume, and underfilled blood bottles are ubiquitous.MethodsBlood bottle fill volumes were measured using an automated monitoring system across multiples sites (10 hospitals, 3 laboratories) within a large suburban/urban health system. Baseline fill volumes were measured for 4 months. A quality improvement program was then implemented over 36 months. Strategies to improve fill volumes included education, standardized data collection, novel and unblinded information cascades, targeted communication, and bottle markings for blood collectors.ResultsA total of 516 201 blood cultures were evaluated over 40 months. In the preimplementation period (January–April 2015), no hospitals collected the recommended 8–10 mL/bottle, and the average system fill volume was 2.3 mL. In the final postimplementation period (January–April 2018), 7 of 10 hospitals achieved ≥8 mL per bottle and the system average increased to 8.6 mL (P < .0001). The positivity rate increased 20%, from 7.39% to 8.85% (P < .001), whereas the contamination rate did not change and remained low. Compared to the preimplementation period, the odds of positive cultures containing potential pathogens increased to 1.18 (95% confidence interval, 1.05–1.32; P = .003).ConclusionsHere we show that underfilled blood cultures are extremely common but that operational and educational strategies can result in sustained improvements across a complex network of hospitals and laboratories. This leads to increased detection of pathogens, which can have tremendous impact on the management of bloodstream infections and sepsis.

Abstract More than 98% of newly diagnosed childhood B-NHL expresses CD20 (Perkins/Cairo, Clin Adv Hem/Onc 2003). The prognosis for children and adolescents with recurrent CD20 positive NHL, particularly DLBCL and BL, is dismal (Cairo et al, Am J Hem, 2003, Cairo et al, Br J Hem, 2003). A radiolabeled anti-CD20 antibody, 90Y-IT, has recently received FDA approval for adults with recurrent indolent CD20+ B-NHL. The dose limiting toxicity in adults has been myelosuppression (Witzig et al, JCO, 2003). Through the COG Phase I Consortium, we evaluated the safety of 90Y-IT in Pts with refractory childhood and adolescent CD20+ lymphoma: DLBCL (n=3) 1st relapse (n=1), 2nd relapse (n=2); refractory BL (n=1); refractory PTLD (DLBCL) (n=1); M:F ratio 4:1, median age 12 yrs (5–18). Pts (n=5) had a minimum of 2 x 106 CD34/kg cryopreserved PBSC. Pts (n=5) received Rituximab 250 mg/m2 IV on Days 0 and 7 and Indium 5 mCi IV on Day 0. Gamma imaging scans and peripheral blood dosimetry studies were performed on Days 0, 1, 3, and 6. Immediately following Rituximab on Day 7 (n=4) or approximately 24 hrs post Rituximab on Day 8 (n=1), Pts received 90Y-IT if dosimetry studies demonstrated ≤2000 cGy exposure to all solid organs and ≤300 cGy to red marrow based on a dose escalation schema stratified by marrow reserve and Plt; 0.4 mCi/kg (dose level 1) (n=3), 0.1 mCi/kg (dose level 1) (post BMT) (n=2). One Pt progressed prior to DLT evaluation. No evaluable pts (n=4) experienced non-hematologic DLT defined as any Grade III or IV non-hematologic toxicity attributable to the investigational agent or hematologic DLT defined as Grade IV ANC or Grade IV thrombocytopenia of > 7 days duration, and an ANC that did not reach ≥500 mm3 and/or platelet count that did not recover to ≥20,000/mm3 by Day 35. The incidence of HAMA/HACA was 0% (n=0). Toxicities related to the 90Y-IT included Grade I muscle pain/abdominal cramping (n=2), Grade III Plts (n=1), Hgb (n=1), infection (n=1), and Grade IV ANC (n=2), Plts (n=1). One Pt experienced Grade II infusion related chills associated with Rituximab. Mean organ radiation exposure (cGy) was as follows: kidneys 341 (112–515), liver 345 (83–714), lungs 309 (155–519), red marrow 46 (20–78), spleen 565 (161–816), and total body 3.7 (2.1 – 4.8). Mean serum quantitative immunoglobulins (mg/dl) at Day 35 were as follows: IgA 65, IgG 394, and IgM 32. 5/5 Pts experienced progressive disease and went on to receive further therapy. In conclusion, 90Y-IT appears to be well tolerated in children and adolescents with recurrent/refractory CD20+ lymphoma and associated with low exposure of radiation to solid organs and marrow. Based on these findings, an investigator-initiated limited institutional Phase II study is planned to further evaluate the safety, tolerability, and response rate with dose stratification based on marrow reserve and Plt: 0.4 mCi/kg (no prior BMT and Plt ≥ 150k), 0.3 mCi/kg (no prior BMT and Plt 100-149 k), 0.2 mCi/kg (prior BMT and Plt ≥ 100k).

Background:Anemia is widespread in rheumatic patients and is an important extra-articular manifestation that correlates with physical disability and increased mortality. The pathogenesis of such anemia is complex and multifactorial, including due to the influence of pro-inflammatory cytokines.Objectives:Our aim was to study the characteristics of the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) with anemia of chronic diseases (ACD), iron deficiency anemia (IDA) and a combination of ACD / IDA, as well as to study the effect of these cytokines on the development of anemia.Methods:There were examined 69 (54 (7 men /47 women, 50.6 ± 4.1 years) with anemia, 15 (6 men/9 women, 53.5 ± 2.74 years) without anemia) of RA patients. According to the criteria of Van Santen and Worwood, by determining the transferrin saturation index (TSI), ferritin, C-reactive protein (CRP), patients were divided into 4 groups: group 1 - ACD, 22 (5/17) patients (hemoglobin 79 [IQR, 95.6-111], red blood cells 3.5 [IQR, 3.6-4], TSI 25 [IQR, 14.7-26.2], ferritin 326.2 [IQR, 197.8-451.7], CRP 63.7 [IQR, 10.2-104.8]), group 2 - ACD / IDA, 18 (0/18) patients (hemoglobin 101 [IQR, 94-114], red blood cells 3.9 [IQR, 4-4.4], TSI 12.5 [IQR, 7.7-15], ferritin 50.1 [IQR, 11.9-74.9], CRP 45.8 [IQR, 17.6-54.9]), group 3 - IDA, 14 (2/12) patients (hemoglobin 108 [IQR, 100-115], red blood cells 4.5 [IQR, 4.1-4.9], TSI 9.7 [IQR 3-14], ferritin 21.8 [IQR, 7.2-28.9], CRP 8.6 [IQR, 2.7-8.6]), group 4 (control) - 15 patients without anemia (hemoglobin 141.4 [IQR, 133-147], red blood cells 4.6 [IQR, 4.3-4.9], TSI 23.1 [IQR, 16.6-27.8], ferritin 78.5 [IQR, 36-90.7], CRP 4.6 [IQR, 1.2-5.8]). The diagnosis of rheumatoid arthritis was made based on the 2010 ACR/EULAR classification criteria. The number of red blood cells and hemoglobin levels were determined on a Sysmex XS-500i analyzer (Japan). Concentrations of ferritin, CRP, TSI were determined on an Olympus Au 480 analyzer (Beckman Coulter, USA). Concentrations of IL-6, IL-10, and TNF-α were determined using a Stat Fax 2100 analyzer (Awareness Technology Inc., USA). The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test at a significance level (p) of less than 0.05. To assess the relationship between the variables, the Spearman correlation coefficient (r) was calculatedResults:In the ACD group, there were the highest concentrations of CRP, ferritin in comparison with the other groups (p <0.05). TSI in the ACD group was higher compared with the IDA and ACD / IDA groups (p <0.05) and did not differ from the control group (p> 0.05). The maximum concentration of IL-6 was found in the ACD group (36.2 [IQR, 6.7-41]) compared with the ACD / IDA group (21.7 [IQR, 7.2-20.4]) (p <0, 05) and the IDA group (5.9 [IQR, 1.5-3.7]) (p <0.05) and without anemia (2.7 [IQR, 1.5-3) (p <0.05). Regarding IL-10 and TNF-α, no intergroup differences were found. A moderate correlation was found between the number of red blood cells and the concentration of IL-6 (r = -0.3), IL-10 (r = -0.4), TNF-α (r = -0.3). The relationship between the concentration of hemoglobin and IL-6 (r = -0.6), IL-10 (r = -0.4), TNF-α (r = -0.3) was revealed.Conclusion:In RA patients, IDA, ACD, as well as their combination, may occur. It is very important to clarify the genesis of anemia. ACD should be isolated separately because it has a complex pathogenesis, one of the important components of which are cytokines and their effect on erythropoiesis. The increased concentration of IL-6 in the group of patients with ACD, as well as the presence of a correlation between IL-6, red blood cells and hemoglobin, indicate the importance of this cytokine in the development of anemia. An increase in the concentration of ferritin and CRP also reflects the inflammatory genesis of anemia in patients with this anemia. The presence of a correlation between IL-10, TNF-α and hemogram indices suggests their influence on the development of anemia.Disclosure of Interests:None declared

ObjectivesTo determine whether a team illness prevention strategy (TIPS) would reduce the incidence of acute illness during the Super Rugby tournament.MethodsWe studied 1340 male professional rugby union player seasons from six South African teams that participated in the Super Rugby tournament (2010–2016). Medical staff recorded all illnesses daily (126 850 player days) in a 3-year control (C: 2010–2012; 47 553 player days) and a 4-year intervention (I: 2013–2016; 79 297 player days) period. A five-element TIPS was implemented in the I period, following agreement by consensus. Incidence rate (IR: per 1000 player days; 95% CI) of all acute illnesses, illness by main organ system, infectious illness and illness burden (days lost due to illness per 1000 player days) were compared between C and I period.ResultsThe IR of acute illness was significantly lower in the I (5.5: 4.7 to 6.4) versus the C period (13.2: 9.7 to 18.0) (p<0.001). The IR of respiratory (C=8.6: 6.3 to 11.7; I=3.8: 3.3 to 4.3) (p<0.0001), digestive (C=2.5: 1.8 to 3.6; I=1.1: 0.8 to 1.4) (p<0.001), skin and subcutaneous tissue illness (C=0.7: 0.4 to 1.4; I=0.3: 0.2 to 0.5) (p=0.0238), all infections (C=8.4: 5.9 to 11.9; I=4.3: 3.7 to 4.9) (p<0.001) and illness burden (C=9.2: 6.8 to 12.5; I=5.7: 4.1 to 7.8) (p=0.0314) were significantly lower in the I versus the C period.ConclusionA TIPS during the Super Rugby tournament was associated with a lower incidence of all acute illnesses (59%), infectious illness (49%) and illness burden (39%). Our findings may have important clinical implications for other travelling team sport settings.

Objectives: to determine the causes of ineffective observation and poor prognosis in patients undergoing ADHF, in real clinical practice and to consider the basics of the formation of specialized medical care for patients with heart failure (HF).Materials and methods: the study was conducted based on the City Center for the treatment of heart failure (center HF), N. Novgorod. The study consistently included 942 patients with heart failure (HF) at the age of 18 years and older who underwent ADHF and received inpatient treatment in center HF between March 4, 2016 and March 3, 2017. Based on the decisions of patients to continue outpatient monitoring in center HF, two groups of patients were distinguished: patients who continued to be monitored in center HF (group I, n = 510) and patients who continued to be monitored in outpatient clinics at the place of residence (group II, n = 432). The assessment of adherence to treatment, overall mortality, survival and re-admission to a depth of two years of observation was carried out. Statistical data processing was performed using Statistica 7.0 for Windows and the software package R.Results: all patients in the study groups had high comorbidity. Group 2 patients turned out to be statistically significantly older, more often had III functional class (FC) HF, lower the baseline test score of 6-minute walk, and higher the baseline clinical assessment scale. After 2 years of follow-up in group II, there was a significant deterioration in adherence to basic therapy of HF compared with group I. According to the results of multifactorial proportional risk Cox models, it was shown that observation of patients in the group 1 is an independent factor increasing the risk of overall mortality by 2.8 times by the end of the second year of observation. Survival after two years of follow-up was: in group I — 89.8 %, and in group II — 70.1 % of patients (OR = 0.3, 95 % CI 0.2 – 0.4; p1/2 < 0.001). After two years of follow-up, the proportion of re-hospitalized patients in group II was greater (78.0 % of patients) versus group 1 (50.6 % of patients, OR = 3.5, 95 % CI 2.6 – 4.6; p1/2 <0.001). The independent risk of re-hospitalization according to multinominal logit regression was 3.4 times higher in group II and 2.4 times for III – IV FC HF. Conclusions: the inclusion of patients with HF in the system of specialized medical care improves adherence to treatment, prognosis of life and reduces the risk of repeated hospitalizations. Patients of an older age and with an initially greater clinical severity refused specialized supervision in center HF.

Background:Gastrointestinal (GI) involvement is common in patients with SSc and may lead to weight loss and malnutrition. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks, with mainly GI adverse events. The Malnutrition Universal Screening Tool (MUST) was developed to identify adults who are at risk of malnutrition and has been used in studies of patients with SSc.Objectives:To evaluate nutritional status over 52 weeks in the SENSCIS trial based on a modified MUST score.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients who had taken a stable dose of mycophenolate for ≥6 months were eligible to participate. Patients were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage adverse events and specific recommendations were provided for the management of diarrhoea. We calculated a modified MUST score at baseline and weeks 12, 24, 36 and 52 based on (A) BMI, (B) weight loss (week 12 vs baseline; week 24 vs week 12; week 36 vs week 24; week 52 vs week 36), and (C) a surrogate for acute disease effect (if the patient had any serious adverse event that led to hospitalisation between weight assessments and received ≥1 medication from the WHO classification code for “solutions for parenteral nutrition” for ≥5 days). MUST score at baseline was based solely on BMI. With scores ranging from 0 to 6, the risk of malnutrition is defined as low (score = 0), medium (score = 1) or high (score ≥2).Results:Among 576 patients who received nintedanib (n=288) or placebo (n=288), mean (SD) age at baseline was 54.0 (12.2) years, weight was 69.7 (15.9) kg and BMI was 25.9 (5.0) kg/m2; median time since onset of first non-Raynaud symptom was 3.4 years; and 75.2% of patients were female. In the nintedanib and placebo groups, respectively, MUST scores suggested that 74.0% and 78.1% of patients were at low risk of malnutrition at baseline and remained at low risk at their last measurement (Table 1). At weeks 12 and 52, respectively, mean (SD) MUST scores were 0.3 (0.6) and 0.4 (0.7) in the nintedanib group and 0.2 (0.5) and 0.2 (0.6) in the placebo group. At weeks 12, 24, 36 and 52, respectively, the proportions of patients at low risk of malnutrition were 81.8%, 80.9%, 72.9% and 76.5% in the nintedanib group and 86.6%, 86.4%, 88.3% and 80.8% in the placebo group; the proportions at medium risk were 12.1%, 13.1%, 18.0% and 13.5% in the nintedanib group and 8.5%, 8.6%, 5.8% and 13.1% in the placebo group; and the proportions of patients at high risk were 6.1%, 5.6%, 8.3% and 9.6% in the nintedanib group and 4.9%, 4.3%, 4.7% and 5.4% in the placebo group.Table 1.Risk of malnutrition at baseline and at last assessment over 52 weeks in the SENSCIS trial.Last assessment of riskNintedanib (n=288)Placebo (n=288)Baseline riskBaseline riskLowMediumHighTotalLowMediumHighTotalLow213 (74.0)1 (0.3)0214 (74.3)225 (78.1)7 (2.4)0232 (80.6)Medium31 (10.8)8 (2.8)039 (13.5)20 (6.9)14 (4.9)4 (1.4)38 (13.2)High13 (4.5)8 (2.8)7 (2.4)28 (9.7)3 (1.0)2 (0.7)10 (3.5)15 (5.2)Missing7 (2.4)007 (2.4)3 (1.0)003 (1.0)Total264 (91.7)17 (5.9)7 (2.4)288 (100)251 (87.2)23 (8.0)14 (4.9)288 (100)MUST score ranges from 0 to 6. Score of 0 = low risk: score of 1 = medium risk; score of ≥2 = high risk. Baseline MUST score was based solely on BMI.Conclusion:In the SENSCIS trial, scores based on a modified MUST indicated that most patients treated with nintedanib were at low risk of malnutrition at baseline and remained at low risk over 52 weeks. The proportions of patients at high risk of malnutrition were low but were numerically greater in patients who received nintedanib than placebo. Management of disease manifestations and gastrointestinal adverse events that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD treated with nintedanib.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Zsuzsanna McMahan: None declared, Sindhu Johnson Consultant of: Boehringer Ingelheim, CSL Behring and Ikaria, Grant/research support from: Bayer, Boehringer Ingelheim, Corbus, GlaxoSmithKline, Merck and Roche, Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Research Foundation - Flanders (FWO) and Janssen, Stéphane Jouneau Speakers bureau: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlaxoSmithKline, LVL Mediphar, Mundipharma, Novartis, Pfizer, Roche and Sanofi, Consultant of: AIRB, Boehringer Ingelheim, Novartis and Roche, Grant/research support from: AIRB, Boehringer Ingelheim, LVL Mediphar, Novartis and Roche, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Ariane Herrick Speakers bureau: Janssen, Consultant of: Boehringer Ingelheim, Camurus, CSL Behring and Gesynta Pharma, Grant/research support from: Actelion and Gesynta Pharma

Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)

В работе предложена модель формирования морфологии тетраподов ZnO,основанная на описании процесса полиморфного перехода от октаэдрических кластеровс кристаллической структурой сфалерита B3 к четырем стрежневым кристаллам со струк-турой вюрцита B4 как разрыва топологического пространства роста на наномасштабе. Примоделировании предкристаллизационного этапа формирования тетраподов в условияхдинамического хаоса частиц методом системы итерированных функций используютсяпараметры отображений, задающих ориентацию топологических пространств роста крис-таллических элементов иерархической структуры тетрапода ЛИТЕРАТУРА1. Tsuneta T., Tanda S. Formation and growth of NbSe3 topological crystals // Journal of Crystal Growth,2004, v. 264(1−3), pp. 223-231. DOI: https://doi.org/10.1016/j.jcrysgro.2003.12.0202. Liu Y., Chen Z., Kang Z., Bello I., Fan X., Ismathullakhan Shafi q, Zhang W., Lee S.-T. 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Abstract Abstract 811 Background: High-dose therapy and autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for many patients (pts) with high-risk or relapsed B-cell non-Hodgkin lymphoma (B-NHL). Despite the use of transplant, relapse is likely for most with indolent or mantle cell lymphoma (MCL) as well as for aggressive B-NHL recurring after rituximab (R)-based chemotherapy. Total body irradiation (TBI) has been incorporated into ASCT regimens to overcome chemotherapy resistance and improve outcomes, but studies to date indicate that escalation of TBI is not feasible due to toxicity in non-target organs. We hypothesized that radioimmunotherapy (RIT) could supplant TBI and identified the maximally tolerated dose (MTD) of high-dose RIT using I-131-tositumomab that could be safely combined with high-dose etoposide (VP-16) and cyclophosphamide (CY) prior to ASCT (Press, Blood 2000). We now present the mature data of a large prospective phase II trial at the MTD of high-dose I-131-tositumomab, VP-16, and CY. Methods: Pts were eligible if they were <60 years of age, had MCL in first remission or any relapsed/refractory B-NHL, an ECOG PS of 0–1, acceptable organ function, >2×106 autologous CD34+ peripheral blood stem cells/kg collected, <20 Gy prior radiation to critical organs, and no human-anti-mouse-antibodies. All pts underwent outpatient biodistribution studies using tositumomab (1.7 mg/kg, n= 64 or 485mg flat dose, n= 43) labeled with ∼10mCi I-131 followed by serial quantitative gamma camera imaging to calculate individualized organ-specific absorbed dose estimates. Pts then received therapeutic infusions of I-131-tositumomab to deliver 25Gy to the critical normal organ receiving the highest radiation absorbed dose. When residual radiation was <7mR/hr at 1m (median 10 days) pts received 60mg/kg VP-16 followed 48 hours later by 100mg/kg CY. ASCT occurred when residual radiation was <2mR/hr at 1m. Toxicity was scored on the Bearman transplant scale and CTCAE 2.0. Response followed standard criteria. Results: Between June 1999 and April 2011 107 pts were transplanted on this protocol. Baseline characteristics included: median age 52 yrs (range 32–60), stage III/IV = 104 (97%), median number of prior regimens = 3 (range 1–11), prior R = 98 (92%), R refractory = 35 (33%), chemoresistant disease (defined as < a partial response [PR] to the most recent regimen) = 41 (40%), >1 extranodal site = 36 (33%), elevated LDH = 46 (42%). Histological strata: Indolent 43% (45 follicular lymphoma [FL], 1 lymphoplasmacytic lymphoma), MCL = 31%, Aggressive 27% (27 diffuse large B-cell including 12 with transformed disease, 2 Burkitt's). Dose limiting critical normal organs receiving up to 25Gy included lung (71), liver (29), kidney (6), and heart (1) from a median administered I-131 activity of 557 mCi (range 231–1353) resulting in a median whole body dose of 4.4Gy. ASCT occurred an average of 14 days after the I-131-tositumomab infusion with a median of 5.9×106 CD34/kg (range 2–20×106 CD34/kg). An unsupported ANC>500/μL and platelets >20K/μL occurred at a median of day 12 and day 13, respectively. Bearman toxicity of grade III/IV was observed in 6 pts (5.6%) with 3 (3%) non-relapse deaths (all cardiopulmonary toxicity) by day 100. Pulmonary toxicity of ≥ grade 4 CTCAE occurred in 10 (9%) pts. Responses to therapy included: CR/CRu = 87 (81%), PR = 8 (7%), SD = 11 (10%), and PD = 1 (1%). Currently, 76 (71%) pts are alive with 59 (55%) progression-free. The estimated 5-year overall survival (OS), progression-free survival (PFS) and relapse were 72%, 56%, and 36%, respectively (figure, median follow up of 5.2 years). Five-year OS/PFS estimates for the 3 histological groups included indolent (81%/61%), aggressive (69%/51%), and MCL (57%/52%). MCL pts with relapsed/refractory disease had a 5-year OS/PFS of 55%/42%. Multivariable analysis only identified chemoresistant disease as associated with death (HR 3.07 (1.46–6.44, p=.003) and relapse or death (HR 2.12 (1.17–3.86, p=.01). Secondary AML/MDS occurred in 1 patient to-date. Conclusions: This largest prospective trial of myeloablative RIT demonstrates that I-131-tositumomab delivering 225Gy to critical organs along with high-dose VP-16 and CY prior to ASCT is feasible and effective with toxicities comparable to TBI-based regimens. These data provide the foundation for future approaches incorporating RIT into transplant conditioning regimens for lymphoma. Disclosures: Gopal: GSK: Research Funding; Spectrum: Research Funding. Off Label Use: high-dose use of I-131-tositumomab. Rajendran:GSK: Research Funding. Pagel:GSK: Research Funding. Maloney:GSK: Research Funding. Press:GSK: Research Funding.

Abstract Introduction: Aberrant DNA methylation occurs frequently in hematologic malignancies and is associated with altered gene expression. Consequently, DNA hypomethylating agents (HMAs), e.g. 5-aza-2'-deoxycytidine (DAC), have been tested for in vivo demethylation and have become accepted as first-line treatment of older MDS and AML patients (pts). While HMAs are already routinely used for the treatment of MDS and AML, only very few outcome predictors have been established thus far. Expression of the β-like globin gene locus is tightly regulated by methylation, is HMA-sensitive in vitro, and fetal hemoglobin (HbF) expression is under study as a potential biomarker for response of MDS pts to 5-azacytidine. Here, we present the first study of serial HbF measurements in MDS and AML pts receiving DAC in order to investigate a potential clinical application of HbF as a predictor of outcome to this treatment. Methods: 16 MDS and 36 AML pts enrolled on two clinical trials, the 06011 EORTC-GMDSSG phase III trial of higher-risk MDS, and the 00331 phase II trial of older, non-fit AML pts (Lübbert M et al., Haematologica 2012), were treated with DAC. MDS pts received nine 4-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for a minimum of four courses. AML pts were treated with nine 3-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for four courses followed by maintenance treatment with DAC at 20 mg/m2 when responding (defined by CR, PR or an antileukemic effect). HbF levels were measured in peripheral blood by HPLC before treatment and sequentially, i. e. after the end of each treatment course (every 6 weeks). HbF levels >1% of total hemoglobin were considered elevated. Results: Baseline HbF was elevated (>1.0%) in 7/16 MDS and 12/36 AML pts. Clinical baseline characteristics were uniformly distributed between pts with normal and elevated HbF levels. HbF induction was observed in 81% of MDS pts after a median of 2 (range 2-6) courses of DAC and in 54% of AML pts after a median of 3 (2-11) courses. Four AML pts receiving standard cytarabine-based induction chemotherapy and four pts with pancreatic cancer receiving gemcitabine-based treatment did not show HbF induction to >1%. When analyzing clinical survival endpoints, elevated baseline HbF was associated with longer median overall survival (OS) for MDS: 26.6 vs. 8.6 months (HR 8.56, 95% CI 1.74-42.49, p=0.008). Similarly, median PFS and AMLFS was prolonged in "HbF high" MDS pts with 15.4 compared to 5.9 months (p=0.016) and 26.3 compared to 8.8 months (p=0.03), respectively. A statistically non-significant trend towards higher HbF baseline values (median 1.5%, range 0.3% to 3.9%) in MDS pts achieving a CR, PR or hematological improvement compared to non-responders (median baseline 0.4%, range 0.1% - 1.9%) was noted. Likewise, OS for AML pts with elevated pre-treatment HbF was prolonged with 10.0 vs. 2.9 months OS (HR 3.01, 95% CI 1.26-7.22, p=0.014). HbF baseline values were comparable in the group that did achieve any response (CR, PR, antileukemic effect) vs. the non-responding group. In a multivariate analysis including LDH and age, the predictive value of HbF was retained. Time-dependent Cox models revealed that the predictive value of treatment-induced HbF induction was markedly inferior to that of baseline HbF. Conclusion: We provide first evidence for in vivo induction of HbF by DAC in MDS and AML pts. Notably, HbF values elevated already prior to treatment harbor highly significant predictive value for survival benefit upon DAC whereas HbF induction is inferior to a stronger effect of pre-treatment HbF. Our findings warrant incorporation of HbF as potential predictive biomarker in larger prospective studies. Disclosures Claus: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Other: Travel Funding. Becker:BMS: Honoraria; Novartis: Honoraria. Lübbert:Ratiopharm: Other: Study drug valproic acid; Janssen-Cilag: Other: Travel Funding, Research Funding; Celgene: Other: Travel Funding.

Background FDG-PET is used in staging and response assessments in patients (pts) with DLBCL. An analysis of 158 pts with DLBCL receiving R-CHOP or DA-EPOCH-R on CALGB/Alliance 50303 failed to show an association between the interim PET (iPET, after cycle 2 of therapy) visual 5-point scale score (5-PS) by central review and progression-free survival (PFS) or overall survival (OS), but did show a significant association between percent change in FDG uptake from baseline to after cycle 2 (∆SUV) and PFS/OS (Schoder et al. 2020). As central review of FDG-PET is not feasible in routine practice, we retrospectively compared local vs central readings, and determined associations from local imaging data with PFS/OS. Methods 126 pts at baseline and 109 at iPET had local imaging data submitted across 21 institutions. Visual scores 1-3 defined PET- and scores 4-5 defined PET+ disease. ∆SUV was defined as the percent change in the maximum SUV at any site (maxSUV) from baseline to iPET. Continuous ∆SUV and categorized ∆SUV (&lt;66% vs &gt;66%) were analyzed. Differences in quantitative measures were calculated as the local minus central result. The Kappa statistic estimated agreement in PET and ∆SUV groups between local and central review. PFS and OS distributions for local PET and ∆SUV groups were landmarked at iPET, estimated with the Kaplan-Meier method, and compared using the log-rank test. Results At baseline, maxSUV was reported locally and centrally in 118 pts. Median maxSUV was 24.3 (range: 5.9-77.3) by local review and 24.3 (range: 5.9-77.0) by central review. The median difference in maxSUV was 0 (range: -12.9 to 21.9), with 50% of differences between -1.1 and 0.1, and 90% of differences between -7.8 and 4.1. In 106 pts with visual iPET 5-PS results, 52 (49.1%) were PET+ by local review and 37 (34.9%) by central review. Agreement in local and central review was moderate (kappa=0.53), occurring in 81 pts (76.4%; 32 PET+ and 49 PET-). Disagreement occurred in 25 patients, 20 with local PET+ but central PET- and 5 with local PET- but central PET+. iPET maxSUV was reported locally and centrally in 90 pts. Median maxSUV was 3.4 (range: 0-18.3) by local review and 3.3 (range: 1.2-18.2) by central review. The median difference in maxSUV was 0 (range: -8.6 to 2.4), with 50% of differences between -0.3 and 0.4, and 90% of differences between -4.4 and 1.8. ∆SUV was calculated in 87 pts. Median ∆SUV was 84.6% (range: -3.0% to 95.9%) by local review and 85.1% (range: -34.9% to 95.8%) by central review. The median difference in ∆SUV was -0.3 (range: -19.6 to 31.9), with 50% of differences between -2.1 and 1.1, and 90% of differences between -7.1 and 12.3. ∆SUV was &lt;66% in 12 (13.8%) pts by local review and 12 pts by central review. Agreement in local and central review was high (kappa=0.81), occurring in 83 pts (95.4%; 10 with ∆SUV &lt;66%, 73 with ∆SUV &gt;66%). Disagreement occurred in 4 pts, 2 in each direction. Using local data, PFS and OS estimates were numerically lower in pts with iPET+ vs iPET- disease, but did not reach statistical significance (p=0.12 and p=0.15). Two-year estimates for PFS were 79% (95% CI 68-91%) and 89% (95% CI 81-98%), and 2-year estimates for OS were 84% (95% CI 75-95%) and 96% (95% CI 91-100%) in pts with iPET+ and iPET-, respectively. In contrast, ∆SUV groups were significantly associated with PFS and OS (p=0.03 and p=0.002). Two-year estimates for PFS were 56% (95% CI 34-94%) and 87% (95% CI 79-95%) and 2-year estimates for OS were 56% (95% CI 34-94%) and 93% (95% CI 88-99%) in pts with ∆SUV &lt;66% and ∆SUV &gt;66%, respectively. Conclusion Agreement in visual 5-PS at iPET was moderate; most discrepancies arose from a local PET+ result when central review called PET-. Differences in maxSUV and ∆SUV tended to be small. Grouping ∆SUV resulted in only 4 discrepancies (4.6%). Similar to the previous analysis using central data, the separation in PFS and OS curves using local data for ∆SUV was greater than by visual 5-PS. Encouragingly, the agreement in ∆SUV of &lt;66% vs ≥66% was high between local and central review. Overall agreement however may be unduly influenced by the large proportion of pts with ∆SUV ≥66%, with less certainty in agreement for pts with ∆SUV &lt;66%. Larger prospective studies comparing local and central imaging data are warranted to best determine the utility of local imaging in clinical trials. Support: P30 CA008748, U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT00118209 (CALGB 50303) Disclosures Kahl: Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Friedberg:Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Portola Pharmaceuticals: Consultancy; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy. Leonard:MEI Pharma: Consultancy; Sutro: Consultancy; Bayer: Consultancy; BMS/Celgene: Consultancy; GenMab: Consultancy; Roche/Genentech: Consultancy; Gilead/Kite: Consultancy; ADC Therapeutics: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; Miltenyi: Consultancy; AstraZeneca: Consultancy; Karyopharm: Consultancy. Bartlett:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Forty Seven: Research Funding; BMS/Celgene: Research Funding; BTG: Consultancy; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Acerta: Consultancy; Affimed Therapeutics: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding.

Abstract Background: Multiple myeloma (MM) and plasma cell dyscrasias (PCD) are associated with increased risk of venous thromboembolism (VTE) which is further enhanced by treatments with immunomodulatory agents, melphalan or steroids. The optimization of VTE prevention in patients with MM is an unmet need. According to Virchow's triad, blood hypercoagulabilty is one of the three conditions required for thrombosis. Elaboration of a risk assessment model, which includes biomarkers of hypercoagulability, could lead to better identification of MM patients eligible for pharmacological thromboprophylaxis. Aims: We conducted a longitudinal observational study, to explore the relationship of MM with cellular and plasma hypercoagulability aiming to identify the most relevant biomarkers which could be used in the RAM for VTE. Materials and Methods: Newly diagnosed patients (n=72) with PCD were recruited from July 2014 to May 2015. The control group (CG) was consisted of 30 healthy age and sex-matched individuals. A systematic compression ultrasound was performed at baseline and 6 months post-therapy. Blood samples were obtained at time of diagnosis and at 3-6 months post therapy. Samples of platelet poor plasma were assessed for thrombin generation (TG) with the PPP-Reagent® (5pMTF and 4μM phospholipids), P-selectin, D-dimers (D-Di), activated FVII (FVIIa), Tissue Factor (TFa), fibrin monomers (FM), and procoagulant phospholipid dependent clotting time (PPL-ct). The upper and lower normal limits (UNL and LNL) were calculated by the mean±2sd. We present herein the data obtained at the inclusion of the patients. Results: Forty-three patients had MM, 16 had asymptomatic MM (AMM), 13 had MGUS. The median age was 68 years (40-84 years); 44% of patients were males. The median time to follow up was 6 months (range: 2-12 months). Patients with PCD as compared to the CG had significantly shorter PPL-ct, which it has been shown that it is inversely correlated with the concentration of platelet derived procoagulant microparticles. PCD patients had also lower Endogenous thrombin potential (ETP), shorter time to thrombin Peak (ttPeak) and lower mean rate index (MRI) of the propagation phase of TG as compared to the controls. The levels of P-selectin were not significantly different between the two groups. Patients with MM as compared to MGUS and AMM patients had significantly higher levels of TFa, FVIIa, FM, D-Di, Peak and MRI (Table 1). Among MM patients 72% had PPL-ct below the LNL, 62% and 28% had TFa and FM above the UNL respectively, 4% had MRI above the UNL and 29% had MRI below the LNL. Among patients who received therapy, 46% also received thromboprophylaxis with either aspirin (76%, n=22) or LMWH (24%, n=5); all were MM patients who received IMiD-based therapies. During the follow-up period the rate of VTE events in MM patients was 7% (all MM patients under treatment). Conclusion: In patients with PCD increased procoagulant microparticles of cellular origin is a generalized phenomenon. In addition, patients with MM present significant TF pathway activation and increased in vivo TG. A significant part, but not all of the patients present strong signs of plasma hypercoagulability. The finding of high inter-individual variability of TG underlines the heterogeneity of blood coagulation alterations in MM patients. The data of the prospective part of this study will allow to validate the clinical significance of this finding. Table 1. Biomarkers of plasma and cellular hypercoagulablity in newly diagnosed patients with PCD. ETP: endogenous thrombin potential; MRI: mean rate index of the propagation phase of thrombin generation. FM: fibrin monomers Parameters Controls (n=30) MGUS (n=13) AMM (n=16) MM (n=43) PPL (sec) 62.8±8.6 38.1±8.2* 41.3±6.8* 39.9±13.7* P-Selectin (pg/ml) 62660±10390 35127±12462 29697.7±9090.45 36223±13638 FTa (ng/ml) 0.3±0.1 2.1±1.4* 1.9±1.3* 7.5±23.3*$ FVIIa (U/ml) 50.9±10.6 60.2±27.5 64.4±48.6 102.1±203.5*$ FM (μg/ml) 3.5±0.8 8.1±8.4* 5.7±1.7* 17.7±38.3*$ D-Di (μg/ml) 0.3±0.1 1.1±1.1 0.6±0.5 1.8±2.8*$ Thrombin generation Lagtime (min) 2.5±0.4 3.4±1.2 3.43±0.71 4.2±2.3*$ ETP (nM/min) 1496±191 1029±205 1045.87±288.9 1202±516$ Peak (nM) 289±36 168±60 174±64 216±74$ ttPeak (min) 5.3±0.7 7.3±1.8 7.17±1.23 7.1±2.7 MRI 110±24 48±24 52±28 82±44$ *p<0.05 versus Controls $p<0.05 versus MGUS and SMM Disclosures Van Dreden: Diagnostica Stago: Employment. Dimopoulos:Janssen-Cilag: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Onyx: Honoraria.

Climate change induced sea-level rise (SLR) is on its increase globally. Regionally the lowlands of China, Vietnam, Bangladesh, and islands of the Malaysian, Indonesian and Philippine archipelagos are among the world’s most threatened regions. Sea-level rise has major impacts on the ecosystems and society. It threatens coastal populations, economic activities, and fragile ecosystems as mangroves, coastal salt-marches and wetlands. This paper provides a summary of the current state of knowledge of sea level-rise and its effects on both human and natural ecosystems. The focus is on coastal urban areas and low lying deltas in South-East Asia and Vietnam, as one of the most threatened areas in the world. About 3 mm per year reflects the growing consensus on the average SLR worldwide. The trend speeds up during recent decades. The figures are subject to local, temporal and methodological variation. In Vietnam the average values of 3.3 mm per year during the 1993-2014 period are above the worldwide average. Although a basic conceptual understanding exists that the increasing global frequency of the strongest tropical cyclones is related with the increasing temperature and SLR, this relationship is insufficiently understood. Moreover the precise, complex environmental, economic, social, and health impacts are currently unclear. SLR, storms and changing precipitation patterns increase flood risks, in particular in urban areas. Part of the current scientific debate is on how urban agglomeration can be made more resilient to flood risks. Where originally mainly technical interventions dominated this discussion, it becomes increasingly clear that proactive special planning, flood defense, flood risk mitigation, flood preparation, and flood recovery are important, but costly instruments. Next to the main focus on SLR and its effects on resilience, the paper reviews main SLR associated impacts: Floods and inundation, salinization, shoreline change, and effects on mangroves and wetlands. The hazards of SLR related floods increase fastest in urban areas. This is related with both the increasing surface major cities are expected to occupy during the decades to come and the increasing coastal population. In particular Asia and its megacities in the southern part of the continent are increasingly at risk. The discussion points to complexity, inter-disciplinarity, and the related uncertainty, as core characteristics. An integrated combination of mitigation, adaptation and resilience measures is currently considered as the most indicated way to resist SLR today and in the near future.References Aerts J.C.J.H., Hassan A., Savenije H.H.G., Khan M.F., 2000. Using GIS tools and rapid assessment techniques for determining salt intrusion: Stream a river basin management instrument. 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Abstract The American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Classification of Cancer 8th edition (AJCC8) was officially introduced in January 2018 as a replacement for the previous version (AJCC7). Validation studies using data obtained from large cancer registries in North America demonstrated the superiority of AJCC8 over AJCC7 for prediction of survival. Subsequent studies from Europe and East Asia have mostly shown similar findings. However, these data may not be generalizable to other parts of the world. In this first study from the Middle East (Saudi Arabia), we compared these two versions of AJCC staging for their concordance and prediction of outcome in a large unselected sample of patients (pts) with DTC managed at a major referral medical center. We also compared the AJCC staging systems with the American Thyroid Association (ATA) Risk Classification. Of 814 consecutive pts seen during this period, 94 were excluded either due to their diagnosis being medullary or anaplastic thyroid cancer (37) or because of deficient data. The remaining 720 pts (149 males (20.7%), 571 females (79.3%) were included. The median age at the diagnosis was 37 yrs (range, 6-83). Total thyroidectomy was performed in 693 pts (96.3%) and central and/or lateral lymph node dissections in 487 pts (67.6%). I-131 was administered to 626 pts (87%). The tumors were classic PTC in 519 pts (72%), follicular variant PTC in 100 (13.9%), Tall cell PTC in 22 (3.1%), diffuse sclerosing PTC in 10 (1.4%), follicular thyroid cancer in 21 (2.9%) and other rare subtypes in 48 pts (6.8%). The number (%) of pts within each stage group by AJCC7 and AJCC8 respectively are as follows: Stage 1: 514 (71.4%) vs. 597 (82.9%), Stage 2: 46 (6.4%) vs. 75 (10.4%), Stage 3: 63 (8.8%) vs. 11 (1.5%), Stage 4: 97 (13.5%) vs. 37 (5.1%). Comparing AJCC8 with the ATA risk stratification system in 709 pts in which data were available, we found a high correlation with 96.8% of ATA low risk group being stage 1 in AJCC8, 2.9% stage 2 and 0.3% stage 3 and none in stage 4. The ATA intermediate risk group was 87.4% AJCC8 stage 1, 12.3% stage 2, 0.4% stage 3 and none in stage 4. The ATA high risk group was 19.1% in AJCC8 stage 1, 33% in stage 2, 9.6% in stage 3 and 38.3% in stage 4. In addition, AJCC8 was more predictive of the outcome with 80% of pts with evidence of disease (biochemically and structurally incomplete) being in AJCC8 stage 3 or 4 compared with 60% in AJCC7. For ATA staging, 8.6%, 22.4% and 67.7% of low, intermediate and high risk groups had evidence of disease at the last follow up, respectively. Conclusion: In this Middle Eastern population, AJCC8 downstaged a significant percentage of pts with DTC from higher stages in AJCC7. It also correlated better with the outcome and with the ATA risk classification system.

Abstract BACKGROUND AND AIMS Conventional haemodialysis (HD) with low-flux membranes does not provide adequate middle molecular weight (MMW) clearance of uremic toxins [1]. The potential for better removal of parathyroid hormone (PTH) and β2-microglobulin (β2M) was investigated using a combination of low-flux HD and haemoperfusion (HP) (HD + HP). METHOD A total of 16 stable HD male patients, free of infections, malignancies or haematological disorders, under usual medications for anaemia and hyperparathyroidism, treated with low-flux polysulfone membranes, were randomized into two groups: group A (GA) included eight patients under HD + HP and group B (GΒ) included eight patients under HD only. In GA patients, a type HA130 HP cartridge was connected in parallel to the dialyzer, once a week for the first month, once every 2 weeks for the second month and once a month for the next 4 months. A third group C (GC) was also studied, consisting of eight males undergoing online haemodiafiltration (OL-HDF). In all three groups, serum β2M and iPTH levels were determined at months 0 and 6, before (preD) and after (postD) the mid-week session. RESULTS Serum preD-β2M levels were similar in groups A and B at month 0 (44.1 ± 8.6 versus 34.6 ± 16.2 mg/L; P = NS) and at month 6 (46.1 ± 7.6 versus 41.1 ± 18.9 mg/L; P = NS). In GC, preD–β2M values were lower compared with GA at month 0 (31.1 ± 4.2 mg/L; P = .008) and at month 6 (33.8 ± 6.82 mg/L; P = .02), and postD–β2M values decreased significantly at month 0 (7.4 ± 1.9 mg/L; P &lt; .001) and at month 6 (9.9 ± 3.8 mg/L; P &lt; 0.001). The reduction was maintained, with no difference between month 0 and month 6. An improvement/decrease in β2M values was observed between month 0 and month 6 only in GA (–5.8 ± 7. 2 versus 1.8 ± 5 mg/L; P = .03) but not in GB. PreD–iPTH values did not differ between groups A, B and C at month 0 (623 ± 432 versus 434 ± 350 versus 710 ± 286 pg/mL, respectively; P = NS) and at month 6 (758 ± 550 versus 383 ± 186 versus 559 ± 296 pg/mL, respectively; P = NS). PostD–iPTH values showed a decrease at month 6 in GA (from 758 ± 550 to 514 ± 474 pg/mL; P = .04) but not in GB and a mild decrease in GC (from 559 ± 296 to 363 ± 295 pg/mL; P = .05), with a marginal reduction improvement between month 0 and month 6 in GC (41 ± 55 versus 196 ± 87 pg/mL; P = .046). CONCLUSION OL-HDF is obviously the most effective method for the elimination of MMW uremic toxins [2]. Interestingly, the combination HD + HP seems to be more effective than low-flux HD alone [3], and it could be useful for specific patient cases in daily clinical practice.