Статті в журналах з теми "612.015 77"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: 612.015 77.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "612.015 77".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Talbot, Elizabeth A., Thomas A. Kenyon, Themba L. Moeti, Gary Hsin, Laura Dooley, Shenaaz El-Halabi, and Nancy J. Binkin. "HIV risk factors among patients with tuberculosis — Botswana 1999." International Journal of STD & AIDS 13, no. 5 (May 1, 2002): 311–17. http://dx.doi.org/10.1258/0956462021925126.
Анотація:
To identify factors associated with HIV in Botswana, a standardized questionnaire was administered to 135 tuberculosis patients with known HIV status. HIV-positive patients were more likely than HIV-negative patients to: be female (45% vs 26% (adjusted prevalence odds ratio (aPOR)=3.8, 95% confidence interval (CI)=1.1-12.7)); be 26-35 years old (50% vs 19% (aPOR=2.7, CI=0.7-10.7)); be unmarried (91% vs 71% (aPOR=13.3, CI=2.5-72.7)); have higher income (24% vs 10% (aPOR=8.2, CI=1.6-42.9)); report separation from spouse/partner for work (63% vs 52% (aPOR=1.8, CI=0.5-6.2)); have 2 sex partners other than their regular partner (82% vs 67% (aPOR=1.8, CI=0.5-7.5)); and state that they or their partner drank alcohol before sex (77% vs 55% (aPOR=6.8, CI=1.9-24.1)). Only 22% of respondents used condoms during all of their past 10 sexual encounters. These data provide information for HIV prevention strategies.
2
Shakeel, Hassan Abdullah, Hamza Maqsood, Basit Ali, and Ali Raza Khan. "Association of chronic viral hepatitis with ABO blood groups and rhesus (Rh) factor." International Journal of Research in Medical Sciences 6, no. 4 (March 28, 2018): 1114. http://dx.doi.org/10.18203/2320-6012.ijrms20181265.
Анотація:
Background: Chronic viral hepatitis includes hepatitis B and hepatitis C and is responsible for causing the deaths of millions of people all across the world each year. Although there are small studies in literature about association between ABO blood groups and chronic viral hepatitis, only few studies found relation between them. The objective of this case control study is to establish a relation between the host factors and these viral infections.Methods: This is a case control study on patients diagnosed with CVHB and CVHC. The study was conducted on 508 patients reported to Nishtar Hospital, Multan and Sheikh Zayd Hospital, Rahim Yar Khan, Pakistan.709 healthy blood donors were selected as a control group from Nishtar Hospital blood bank during December 2016 and December 2017.The results were subjected to SPSS v.20 for analysis using the chi square test. The patients and blood donors were also asked about certain demographic factors like age, sex and blood transfusions.Results: Among CVHB patients,173(100%), the distribution of blood groups was following: Group A, 38 (21.96%), B, 57 (32.94%), AB, 11 (6.35%), O, 67 (38.72%). 158 (91.32%) were Rh positive and 15 (8.67%) Rh negative. In CVHC patients, 335 (100%), the distribution was following: Group A, 69 (20.59%), B, 123 (36.71%), AB, 24 (7.16%), O, 119 (35.52%). 303 (90.44%) were Rh positive while 32 (9.55%) were Rh negative. In healthy blood donors, 167 (23.55%) were group A, 225 (31.73%) group B, 41(5.78%) group AB, 276 (38.92%) group O.632 (89.13%) were Rh positive and 77 (10.86%) Rh negative.Conclusions: There was no significant difference between blood groups(p>0.5) and Rh(p>0.5) with chronic viral hepatitis. However, it was also observed that the infections of HCV increase among (26-45) years old patients while the HBV infections increase with progression of age. Association of chronic viral hepatitis infection with blood group types needs more studies to get more knowledge about this aspect.
3
Bagga, Neha, Poonam Elhence, Meenakshi Rao, Aasma Nalwa, Sudeep Khera, Jyotsna Naresh Bharti, Pratibha Singh, and Shashank Shekhar. "A prospective study of cervical lesions diagnosed by liquid based cytology in Western Rajasthan, India population." International Journal of Research in Medical Sciences 7, no. 12 (November 27, 2019): 4573. http://dx.doi.org/10.18203/2320-6012.ijrms20195521.
Анотація:
Background: Carcinoma cervix is the second most common malignancy of women in India after breast cancer. The present study was conducted to determine the spectrum of cervical lesions by liquid-based cytology in Western Rajasthan population.Methods: It is a Prospective study on 1087 cervical samples carried over a period of 1 year. Cervical samples were taken and processed by SurePath™ LBC.Results: Of total 1087 cases 959 were negative for intraepithelial lesion or malignancy (88.22%). 88 cases (8.09%) were reported as unsatisfactory. Among the non- neoplastic cases- bacterial vaginosis was reported in 209 cases (21.8%), Candida in 77 cases (8.02%), both Candida and bacterial vaginosis in 12 cases (1.25%), reactive cellular changes in 193 cases (20.12%), and Trichomonas vaginalis in 01 case. Among pre-malignant and malignant lesions, 40 cases (4.17%) the distribution was as follows-atypical squamous cells of undetermined significance 16(1.67%), atypical squamous cell-cannot rule out high grade 08 cases (0.83%), Low grade squamous intraepithelial lesion 04 cases (0.42%), high grade squamous intraepithelial lesion 07 cases (0.73%), Atypical glandular cell favoring neoplastic 01 case (0.15%), and squamous cell carcinoma 04 cases (0.42%). Histopathological co-relation of premalignant and malignant lesions was further studied.Conclusions: Liquid based cytology is an effective screening and diagnostic procedure for cervical abnormalities. Among pre-malignant and malignant lesions, histo-pathological correlation increased with increased grade of severity of lesions. To the best of knowledge, this is the largest study of liquid based cytology in the Western Rajasthan.
4
Aushev, Vasily N., Kalpana Gopalakrishnan, Susan L. Teitelbaum, Humberto Parada Jr, Regina M. Santella, Marilie D. Gammon, and Jia Chen. "Tumor expression of environmental chemical-responsive genes and breast cancer mortality." Endocrine-Related Cancer 26, no. 12 (December 2019): 843–51. http://dx.doi.org/10.1530/erc-19-0357.
Анотація:
Environmental phenols and phthalates are common ingredients in personal care products and some have been implicated in breast cancer progression. We have previously identified genes differentially expressed in response to low-dose exposure to diethyl phthalate (DEP) and methyl paraben (MPB) in a rat model. Herein we explore if these genes are associated with breast cancer mortality in humans. We profiled MPB- and DEP-responsive genes in tumors by NanoString® from a population-based cohort of 606 women with first primary breast cancer among whom 119 breast cancer-specific deaths occurred within 15+ years of follow-up. For each gene, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results were validated in two publicly available datasets. The following results were obtained. From 107 DEP- and 77 MPB-responsive genes profiled, 44 and 30 genes, respectively, were significantly associated with breast cancer-specific mortality. Some top DEP-responsive genes are novel for breast cancer mortality, such as ABHD14B (for high-vs-low expression, HR 0.36, 95% CI: 0.2–0.5) and TMC4 (HR 0.37, 95% CI: 0.3–0.5); top hits for MPB (SLC40A1 (HR 0.37, 95% CI: 0.3–0.5) and NTN4 (HR 0.39, 95% CI: 0.3–0.6)) are well-known predictors of breast cancer survival. PLEKHA6 was another novel survival predictor, sensitive to hormonal receptor status (HR 0.5, 95% CI 0.3–0.9 for hormonal receptor-positive and HR 3.2, 95% CI 1.7–6.2 for -negative group). In conclusion, tumor expression of DEP- and MPB-responsive genes is associated with breast cancer mortality, supporting that exposure to these chemicals may influence the progression of breast cancer.
5
Morschhauser, Franck, John Radford, Achiel Van Hoof, Umberto Vitolo, Pierre Soubeyran, Herve Tilly, Peter C. Huijgens, et al. "Phase III Trial of Consolidation Therapy With Yttrium-90–Ibritumomab Tiuxetan Compared With No Additional Therapy After First Remission in Advanced Follicular Lymphoma." Journal of Clinical Oncology 26, no. 32 (November 10, 2008): 5156–64. http://dx.doi.org/10.1200/jco.2008.17.2015.
Анотація:
PurposeWe conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 (90Y)–ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission.Patients and MethodsPatients with CD20+stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive90Y-ibritumomab tiuxetan (rituximab 250 mg/m2on day −7 and day 0 followed on day 0 by90Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment.ResultsA total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers.90Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After90Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with90Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients.ConclusionConsolidation of first remission with90Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.
6
Purvis, Peter, Calvin Chong, and Glen P. Lumis. "Recirculation of nutrients in container nursery production." Canadian Journal of Plant Science 80, no. 1 (January 1, 2000): 39–45. http://dx.doi.org/10.4141/p99-012.
Анотація:
This study evaluated (a) the capacity of a computerized injector to deliver and recirculate nutrients in a container nursery, and (b) plant growth and nutrient status under this regime compared with non-recirculated methods of fertilization, using Dart's Gold ninebark (Physocarpus opulifolius L. 'Dart's Gold') potted in 6-L containers filled with a medium of pine bark, peat, and soil (75, 15, and 10%, by volume). The injector was programmed to deliver NH4-N (24 mg L−1), NO3-N (196 mg L−1), P (54 mg L−1), and K (235 mg L−1) and other nutrients, with or without recirculation. Plants grown with recirculated nutrients were placed on aluminium troughs to collect the leachate, which was pumped back to the injector, recharged [based on a target electrical conductivity (EC) value of 1.85 dS m−1], and returned to the crop. Additional plants were grown on a crushed stone base and fertilized (a) by the computerized injector without recirculation, (b) with water soluble Plant-Prod 20-8-20 (200 mg L−1 N; non-recirculated) delivered through a Dosatron proportioner, or (c) with incorporated, controlled release Nutricote 18-6-8, Type 140 (6.5 kg m−3). NH4-N, NO3-N, P, and K concentrations delivered by the computerized injector (recirculated and non-recirculated; mean over six dates, 3 July to 28 August 1997) were 50, 22, 41, and 39%, respectively, lower than targeted values. Electrical conductivity values were not significantly different from targeted. The pH values (6.2 – 6.4) were higher than targeted (6.0). The amounts of N, P, and K used were reduced by between 57 and 77% with recirculation compared to without. Notwithstanding reduced N, P, and K values, plants grew best with recirculated nutrients and least with non-recirculated liquid 20-8-20. Key words: Fertigation, Harrow Fertigation Manager, recycling, woody ornamentals
7
Jiménez-Reyes, Pedro, Fernando Pareja-Blanco, Carlos Balsalobre-Fernández, Víctor Cuadrado-Peñafiel, Manuel A. Ortega-Becerra, and Juan J. González-Badillo. "Jump-Squat Performance and Its Relationship With Relative Training Intensity in High-Level Athletes." International Journal of Sports Physiology and Performance 10, no. 8 (November 2015): 1036–40. http://dx.doi.org/10.1123/ijspp.2014-0545.
Анотація:
Purpose:To examine the relationship between the relative load in full squats and the height achieved in jump-squat (JS) exercises and to determine the load that maximizes the power output of high-level athletes.Method:Fifty-one male high-level track-and-field athletes (age 25.2 ± 4.4 y, weight 77. ± 6.2 kg, height 179.9 ± 5.6 cm) who competed in sprinting and jumping events took part in the study. Full-squat 1-repetition-maximum (1-RM) and JS height (JH) with loads from 17 to 97 kg were measured in 2 sessions separated by 48 h.Results:Individual regression analyses showed that JH (R2 = .992 ± .005) and the jump decrease (JD) that each load produced with respect to the unloaded countermovement jump (CMJ) (R2 = .992 ± 0.007) are highly correlated with the full-squat %1-RM, which means that training intensities can be prescribed using JH and JD values. The authors also found that the load that maximizes JS’s power output was 0%RM (ie, unloaded CMJ).Conclusions:These results highlight the close relationship between JS performance and relative training intensity in terms of %1-RM. The authors also observed that the load that maximizes power output was 0%1-RM. Monitoring jump height during JS training could help coaches and athletes determine and optimize their training loads.
8
König, Matthias Alexander, and Volker Alexander Braunstein. "Tendon Repair Leads to better Long-Term Clinical Outcome than Debridement in Massive Rotator Cuff Tears." Open Orthopaedics Journal 11, no. 1 (July 25, 2017): 546–53. http://dx.doi.org/10.2174/1874325001611010546.
Анотація:
Introduction: Massive tears in the rotator cuff are debilitating pathologies normally associated with loss of function and pain. Tendon reconstruction is seen as the standard treatment in order to preserve shoulder function and to inhibit cuff associated osteoarthritis. However, the effect on longer-term shoulder function and patient satisfaction is unknown. Material and Methods: 165 consecutive patients with massive tears were included. 57 debridement (mean age 61.9±8.7 years (range 43-77)) and 108 reconstruction (mean age 57.5±8.9 years (range 45-74)) cases could be followed up 2-4 (short-term), 5-6 (mid-term) and 8-10 (long-term) years after surgery. Evaluation was performed with the Constant, a modified ASES and the DASH score. Statistical analysis was done using Sigma-Stat Version 3.5 with a p-value<0.05 indicating statistical significant differences. Results: All three scoring systems showed no significant differences in the short-term follow-up for the two groups (mean values: Constant debridement/repair: 70±11.9/66±13.6; ASES debridement/repair: 22.3±3.3/ 23.3±3.3; DASH debridement/repair: 22.3±11.0/ 24.3±10.1). In the mid-term (Constant debridement/repair: 51±2.9/68.3±5.2; ASES debridement/repair: 20.3±1.3/24.3±1.7; DASH debridement/repair: 31.0±6.5/20.3±5.4) and long-term follow-up (Constant debridement/repair: 42.3±3.8 /60.7±2.6, ASES debridement/repair: 17.3±0.5/21.7±0.5, DASH debridement/repair: 41.3±6.2/25.0±1.4), rotator cuff reconstruction revealed better objective results and better patients’ satisfaction. Conclusion: Rotator cuff tendon repair leads to better long-term clinical outcome and subjective satisfaction compared to debridement. Tendon reconstruction should be considered as a treatment for patients suffering from massive rotator cuff tears, thus preserving shoulder function and by that means delay indication for reverse arthroplasty.
9
Rabeeah, Zainab, Nida Shaikh, and Solveig Cunningham. "Changes in International Students’ Dietary Habits, Physical Activity and BMI During Their First Year After Relocating to the U.S." Current Developments in Nutrition 5, Supplement_2 (June 2021): 680. http://dx.doi.org/10.1093/cdn/nzab045_062.
Анотація:
Abstract Objectives To identify changes in diet, physical activity and BMI after 3–6 months of relocation among international students in Georgia, USA. Methods Data were collected from 74 international students attending 2 urban universities in the Southeast. Students were interviewed within 10 days of arrival in the U.S and again 3–6 months later. Participants completed an interviewer-administered questionnaire that included a 26-item food frequency questionnaire, and questions on weekly physical activity, daily screen-time usage, sleep duration, and anthropometric measurements (body weight, height, and waist circumference), each measured twice and then averaged. Student t-test, Chi square and ANOVA analysis was done for participants who completed both waves (n = 74). Results Participants reported consistent food consumption within 3–6 months (mean difference < 0.5 times per week). Physical activity frequency remained consistent (mean difference < 0.5), but duration of almost all activities was increased. Participants reported increased hiking frequency and a significant increase in duration (frequency mean 0.05 to 0.09 times/week, 95% CI of (0.02–0.08) to (0.02–0.16), duration mean 21.1 to 117 minutes/week, 95% CI (14.1–28.0) to (94.7–138.5)). Screen time significantly increased (mean 4.2 to 7.0 hours/day, 95% CI (3.6–4.9) to (6.2–7.8)). Mean weight slightly increased (62.7 kg to 62.9 kg, 95% CI (60.5–65.0)), as did mean BMI (22.4 to 22.6, 95% CI (21.6–23.2)). However, around 37% of participants gained > 10% of their baseline weight, while 32% lost > 10% of their baseline weight. Almost half of participants (44.5%) reported that they had gained weight and 77% reported a decrease in their overall health. Conclusions Follow-up data suggests International students’ body weights changed drastically in a short time period which could potentially lead to negative health outcomes. Funding Sources None.
10
Millis, Sherri Z., David Bryant, Gargi Dan Basu, Ryan Bender, Semir Vranic, Zoran Gatalica, and Nicholas J. Vogelzang. "Molecular profiling of infiltrating urothelial carcinoma of the bladder." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 311. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.311.
Анотація:
311 Background: Infiltrating urothelial carcinoma (UC) is the most common variant of urinary bladder cancer. The prognosis for muscle infiltrating or metastatic UC of the bladder is poor with no major advances made in the last 20 years. We investigated a large cohort of such patients for specific genetic/biomarker alterations and compared them to other, less common urothelial malignancies. Methods: We reviewed 602 cases; 518 cases (86%) were locally advanced or metastatic UCs of the bladder and the remaining 84 cases (14%) were non-bladder UCs. Multiple methodologies for optimal assessment of biomarker expression (Caris Molecular Intelligence, Caris Life Sciences, Phoenix, AZ) were employed: Mutation analysis (Next-generation sequencing, Sanger, pyrosequencing, qPCR, RFLP), in-situ hybridization (fluorescent and chromogenic), immunohistochemistry, and RNA fragment analysis. Results: Bladder UC showed slightly higher rates of HER2/neu gene amplification (12% in bladder vs. 6% non-bladder, p=0.32) and EGFR gene amplification (22% vs. 12%, p=0.25). HER2/neu and EGFR protein expressions were more common in the bladder than in non-bladder sites (10% vs. 1%, p=0.03, and 77% vs. 60%, p=0.5, respectively). Pathogenic mutations in HER2/neu and EGFR were rare. Although c-Kit and c-Met receptor kinases were more frequently overexpressed in bladder than in non-bladder cancers (10% vs. 6% and 25% vs. 8%, respectively), activating mutations were also rare. PIK3CA and/or PTEN mutations were more frequently observed in non-bladder (27%) than in bladder UCs (21%). Non-bladder UC harbored high FGFR3 gene mutation (33%), which was not observed in any of the UC of the bladder (p=0.02). TP53 gene mutations were frequently identified in both bladder and in non-bladder cancers (49% vs. 27%, respectively, p=0.15), while KRAS was frequently mutated in the bladder adenocarcinomas (56%, p<0.001). Other therapeutically targetable biomarkers over-expressed in bladder UC compared to non-bladder UC included androgen receptor (16% vs. 8%, p=0.07) and MGMT (63% vs. 47%). Conclusions: Comprehensive molecular profiling of urothelial carcinoma identifies a number of potentially actionable targets, which can be managed by the novel treatment modalities.
11
Pollard, Jessica A., Todd A. Alonzo, Michael Loken, Robert B. Gerbing, Phoenix A. Ho, Irwin D. Bernstein, Susana C. Raimondi, et al. "Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML." Blood 119, no. 16 (April 19, 2012): 3705–11. http://dx.doi.org/10.1182/blood-2011-12-398370.
Анотація:
Abstract CD33 is expressed on the majority of acute myeloid leukemia (AML) leukemic blasts and is the target for gemtuzumab ozogamicin (GO), a toxin-conjugated anti-CD33 mAb. In the present study, we quantified the CD33 mean fluorescent intensity of leukemic blasts prospectively in 619 de novo pediatric AML patients enrolled in Children's Oncology Group GO-containing clinical trials and determined its correlation with disease characteristics and clinical outcome. CD33 expression varied more than 2-log fold; a median mean fluorescent intensity of 129 (range, 3-1550.07) was observed. Patients were divided into 4 quartiles, quartiles 1-4 (Q1-4) based on expression and disease characteristics and clinical response defined across quartiles. High CD33 expression was associated with high-risk FLT3/ITD mutations (P < .001) and was inversely associated with low-risk disease (P < .001). Complete remission (CR) rates were similar, but patients in Q4 had significantly lower overall survival (57% ± 16% vs 77% ± 7%, P = .002) and disease-free survival from CR (44% ± 16% vs 62% ± 8%, P = .022). In a multivariate model, high CD33 expression remained a significant predictor of overall survival (P = .011) and disease-free survival (P = .038) from CR. Our findings suggest that CD33 expression is heterogeneous within de novo pediatric AML. High expression is associated with adverse disease features and is an independent predictor of inferior outcome. The correlation between CD33 expression and GO response is under investigation. These studies are registered at www.clinicaltrials.gov as NCT00070174 and NCT00372593.
12
Germaine, Steve, Drew Ignizio, Doug Keinath, and Holly Copeland. "Predicting Occupancy for Pygmy Rabbits in Wyoming: An Independent Evaluation of Two Species Distribution Models." Journal of Fish and Wildlife Management 5, no. 2 (August 1, 2014): 298–314. http://dx.doi.org/10.3996/022014-jfwm-016.
Анотація:
Abstract Species distribution models are an important component of natural-resource conservation planning efforts. Independent, external evaluation of their accuracy is important before they are used in management contexts. We evaluated the classification accuracy of two species distribution models designed to predict the distribution of pygmy rabbit Brachylagus idahoensis habitat in southwestern Wyoming, USA. The Nature Conservancy model was deductive and based on published information and expert opinion, whereas the Wyoming Natural Diversity Database model was statistically derived using historical observation data. We randomly selected 187 evaluation survey points throughout southwestern Wyoming in areas predicted to be habitat and areas predicted to be nonhabitat for each model. The Nature Conservancy model correctly classified 39 of 77 (50.6%) unoccupied evaluation plots and 65 of 88 (73.9%) occupied plots for an overall classification success of 63.3%. The Wyoming Natural Diversity Database model correctly classified 53 of 95 (55.8%) unoccupied plots and 59 of 88 (67.0%) occupied plots for an overall classification success of 61.2%. Based on 95% asymptotic confidence intervals, classification success of the two models did not differ. The models jointly classified 10.8% of the area as habitat and 47.4% of the area as nonhabitat, but were discordant in classifying the remaining 41.9% of the area. To evaluate how anthropogenic development affected model predictive success, we surveyed 120 additional plots among three density levels of gas-field road networks. Classification success declined sharply for both models as road-density level increased beyond 5 km of roads per km-squared area. Both models were more effective at predicting habitat than nonhabitat in relatively undeveloped areas, and neither was effective at accounting for the effects of gas-energy-development road networks. Resource managers who wish to know the amount of pygmy rabbit habitat present in an area or wanting to direct gas-drilling efforts away from pygmy rabbit habitat may want to consider both models in an ensemble manner, where more confidence is placed in mapped areas (i.e., pixels) for which both models agree than for areas where there is model disagreement.
13
Porel, T., S. DE Almeida Chaves, D. Adoue, L. Astudillo, D. Ribes, G. Prévôt, F. Gaches, et al. "SAT0339 NERVOUS SYSTEM INVOLVEMENT IN SYSTEMIC SCLEROSIS: A COHORT STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1115.2–1115. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6142.
Анотація:
Background:Nervous system involvement is considered to be rare in systemic sclerosis (SSc). Its prevalence is highly variable in SSc cohort studies and its prognosis is not well established.Objectives:To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) and central nervous system (CNS) disease in a cohort of systemic sclerosis patients.Methods:We have carried out a retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital, south west France. We included patients who met the following inclusion criteria: being over 18 years of age on diagnosis, meeting the ACR /EULAR 2013 classification criteria, being diagnosed after 01/01/1966 and before 31/12/2018, at least 12 months of follow-up. Patients were followed until 31/12/2019. Nervous system involvement associated with SSc was included when there was involvement on or after diagnosis and after exclusion of all other causes. Only symptomatic clinical involvement was included. Ischemic or hemorrhagic strokes were excluded. We calculated the incidence of CNS and/or PNS disease during the follow-up period per 1,000 person-years. Kaplan-Meier curves were plotted to determine the cumulative incidence of nervous system disease. We evaluated associated factors of CNS and/or PNS disease using multivariable Cox regression.Results:Of 447 SSc patients, 79.8% were female, 68 (15%) were diffuse cutaneous SSc, 342 (77%) were limited cutaneous SSc and 37 (8%) were sine scleroderma SSc. The mean ± SD age at diagnosis was 52.9 ± 14.3 years.During the study period, 82 (18%) patients experienced a PNS disease, 29 (6%) a CNS disease. The incidence was 28 per 1,000 patient-years of any nervous system disease, with 22 per 1,000 patient-years and 6 per 1,000 patient-years of PNS disease and CNS disease, respectively. The most frequent were carpal tunnel syndrome (63%) and polyneuropathies (12%) for PNS disease, and headache (45%) and seizures (10%) for CNS disease.Three significant independent associated factors with PNS disease occurrence were identified using multivariable Cox regression: BMI>23.1kg/m2(HR = 1.06 [1.01-1.12]), joint involvement (HR = 2.7 [1.3-5.5]), and an alteration in the left ventricular ejection fraction (HR = 3.8 [1.4-10.3]).Four significant independent associated factors with CNS disease occurrence were identified: age > 54 years (HR = 2.5 [1.1-6.0]), positive anti-PmScl testing (HR = 6.4 [1.5-28.2]), Caucasian origin (HR = 0.2 [0.1-0.5]) and hemoglobin < 12g/dl (HR = 0.2 [0.04-0.8]).Nervous system disease occurrence did not appear to have a negative impact on the survival of SSc patients (log-rank p=0.56).Conclusion:This study shows that specific nervous system disease in SSc is not uncommon and does not appear to increase mortality, but it could have an impact on functional prognosis and needs to be monitored.Disclosure of Interest:None declared
14
Pekov, Igor V., Vasiliy O. Yapaskurt, Dmitry I. Belakovskiy, Marina F. Vigasina, Natalia V. Zubkova, and Evgeny G. Sidorov. "New arsenate minerals from the Arsenatnaya fumarole, Tolbachik volcano, Kamchatka, Russia. VII. Pharmazincite, KZnAsO4." Mineralogical Magazine 81, no. 4 (August 2017): 1001–8. http://dx.doi.org/10.1180/minmag.2016.080.146.
Анотація:
AbstractThe new mineral pharmazincite, KZnAsO4, was found in sublimates of the Arsenatnaya fumarole at the Second scoria cone of the Northern Breakthrough of the Great Tolbachik Fissure Eruption, Tolbachik volcano, Kamchatka, Russia. It is closely associated with shchurovskyite, dmisokolovite, bradaczekite, arsmirandite, tilasite, johillerite, tenorite, hematite, aphthitalite and As-bearing orthoclase. Pharmazincite occurs as prismatic to acicular crystals up to 1 mm long and up to 0.03 mm thick typically combined in near parallel, radial or chaotic intergrowths, open-work aggregates or crusts up to 2 mm across. Pharmazincite is colourless to white, transparent, with a vitreous lustre. It is brittle, with a stepped fracture and a perfect cleavage parallel to [001]. Dcalc is 4.75 g cm–3. Pharmazincite is optically uniaxial (–),ω = 1.649(2), ε = 1.642(2). The Raman spectrum is reported. The chemical composition (wt.%, electron-microprobe data) is: K2O 18.98, CaO 0.14, MgO 1.20, CuO 4.41, ZnO 27.58, Fe2O3 0.15, P2O5 0.50, As2O546.67, total 99.63. The empirical formula, calculated based on 4 O apfu, is: (K0.97Ca0.01)∑0.98(Zn0.82Cu0.13Mg0.07Fe0.013+)∑1.03(As0.98P0.02)∑1.00O4.The strongest reflections of the powder X-ray diffraction pattern [d,Å(I)(hkl)] are: 6.36 (28)(111), 4.64(45)(220), 4.35(48)(002), 3.260(36)(411), 3.179(100)(222), 2.770(26)(113), 2.676(77)(600), 2.278(15)(602) and 1.710(15)(713, 115). Pharmazincite is hexagonal, a = 18.501(4), c = 8.7114(9) Å, V = 2582.4(8) Å3 and Z = 24 (single-crystal XRD data). Its space group is P63, by analogy with synthetic KZnAsO4 that has a crystal structure based upon a tetrahedral tridymite-type{ZnAsO4}– framework. It is isostructural with megakalsilite KAlSiO4. The new mineral is named for its chemical constituents.
15
Garassino, Marina Chiara, Shirish M. Gadgeel, Delvys Rodriguez-Abreu, Enriqueta Felip, Emilio Esteban, Giovanna Speranza, Maximilian Hochmair, et al. "Evaluation of blood TMB (bTMB) in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) with pemetrexed and platinum versus placebo plus chemo as first-line therapy for metastatic nonsquamous NSCLC." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 9521. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.9521.
Анотація:
9521 Background: In a previous analysis of KEYNOTE-189 (NCT02578680), we showed that tissue TMB (tTMB) assessed by whole-exome sequencing was not significantly associated with efficacy in either arm and that pembro + chemo improved outcomes vs placebo + chemo in both the tTMB ≥175 and tTMB < 175 mut/exome subgroups. Here, we explored the association of bTMB with efficacy in KEYNOTE-189. Methods: 616 patients (pts) were randomized 2:1 to pembro + chemo or placebo + chemo. bTMB was assessed in cfDNA using the Guardant Health Omni assay. Association of bTMB (continuous square root transformed) with outcomes in each arm was assessed using Cox proportional hazards models (OS, PFS) and logistic regression (ORR) adjusted for ECOG PS; statistical significance was determined at the 0.05 level without multiplicity adjustment. The clinical utility of bTMB on outcomes was assessed using the cutoff that most closely approximated the 175 mut/exome tTMB cutoff as determined by AUROC analysis. Data cutoff was 21 Sep 2018. Results: 235 (38%) treated pts had evaluable tTMB and bTMB: 160 in the pembro + chemo arm and 75 in the placebo + chemo arm. bTMB as a continuous variable was not significantly associated with OS or ORR for pembro + chemo (one-sided P = .229 and .051) or placebo + chemo (two-sided P = .641 and .069); bTMB was significantly associated with PFS in the pembro + chemo arm (one-sided P = .015) but not the placebo + chemo arm (two-sided P = .058). bTMB and tTMB scores were moderately correlated (r = .61). The bTMB cutoff that most closely approximated tTMB 175 mut/exome was 15 mut/Mb (AUROC 0.81, 95% CI 0.75-0.86). 178 (76%) pts had concordant bTMB and tTMB results—101 low and 77 high by both—whereas 57 (24%) had discordant results—21 high bTMB but low tTMB, 36 low bTMB but high tTMB. Pembro + chemo improved OS, PFS, and ORR vs placebo + chemo for bTMB ≥15 and < 15 mut/exome (Table). Conclusions: Similar to previous findings based on tTMB, bTMB has limited clinical utility in the setting of pembro with pemetrexed and platinum given as first-line therapy for metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [Table: see text]
16
Wong, Trisha E., Meghan Delaney, Terry B. Gernsheimer, Dana C. Matthews, Tom Brogan, Rob Mazor, D. Michael McMullan, Alexander P. Reiner, and Barbara A. Konkle. "Antithrombin Concentrate Use in Pediatric Extracorporeal Membrane Oxygenation: A Retrospective Cohort Study." Blood 120, no. 21 (November 16, 2012): 1170. http://dx.doi.org/10.1182/blood.v120.21.1170.1170.
Анотація:
Abstract Abstract 1170 BACKGROUND: Many complications, particularly hematological ones, affect the outcome of children on extracorporeal membrane oxygenation (ECMO). In an effort to minimize clotting and bleeding complications, some pediatric ECMO centers administer antithrombin (AT) concentrate to augment heparin's anticoagulant activity. However, the impact on clinical outcomes is unclear. OBJECTIVE: To investigate whether intermittent AT concentrate administration improves outcome in pediatric ECMO patients METHODS: This is a retrospective cohort analysis of 64 youths aged 0 to 21 years who received ECMO for respiratory failure at a single institution between 1/2007 and 9/2011. Subjects either received 1+ dose of plasma-derived AT concentrate (Thrombate III®, Grifols) at the discretion of the attending critical care physician (“AT+” cohort), typically for an AT antigen level <80% with either a high unfractionated heparin (UFH) need or ex vivothrombosis, or did not (“No AT” cohort). Dose was calculated to obtain an AT antigen target level of 120% (IU = [(120-AT level) × weight (kg)]/1.4). AT antigen levels were assayed by an immuno-turbidimetric method (Liatest® ATIII, Stago). Short-term increase in AT antigen levels was the primary endpoint. Secondary endpoints included UFH requirement, number of bleeding and thrombotic complications, number of ECMO circuit changes, length of stay and in-hospital mortality. RESULTS: Of 64 subjects, 30 subjects in the AT+ cohort received a total of 77 AT doses (range 1–8 doses/pt) while the No AT cohort contained 34 subjects. For the AT+ and No AT cohort, respectively: median age was 0.1 (range 0–188) mos. vs 1.7 (0–250) mos. (p=0.21); median first AT level was 50.5% (15–75) vs 54% (19–108, p=0.48); and median ECMO duration was 180 (71–613) hrs vs 146 (44–1,467) hrs (p=0.76). When comparing all AT levels drawn within 12 hrs of a prior measurement, AT antigen was on average 66% in the AT+ cohort compared to 42.2% in the No AT cohort [23.8% higher in AT+; 95% confidence interval (CI), 10.2 – 37.5%], adjusted for age, ECMO duration and first AT level. When comparing only the first AT level drawn within 12 hrs of a prior measurement after an AT dose, AT levels were on average 80.1% in the AT+ cohort compared to 41.7% in patients in the No AT cohort (38.4% higher in AT+; 95% CI, 36.1 – 45.2%). Only 6 of 77 doses reached the targeted AT level of 120% (8%). Of the 28 doses after which the AT level was followed sufficiently, median time to fall to an AT level of 80% was 6.8hrs after receiving the dose (mean: 9.8 hrs, Figure 1). For the AT+ cohort, mean UFH rate decreased by 10.1 u/kg/hr for the 3hrs following the AT dose (95% CI, 7.6–36.6; p<0.001) compared to the 3hrs prior. The UFH rate remained significantly lower 12hrs following administration (10.2 u/kg/hr lower; 95% CI, 6.2–14.1; p=<0.001). No significant differences existed in the number of patients with an in vivo thrombosis (14.7% vs. 13.3%, p=1.0); hemorrhagic complications (0.14 more bleeds in AT+ vs. No AT cohort; 95% CI, −0.34–0.63; p=0.56); number of circuit changes (0.15 changes more in AT+; 95% CI −0.002–0.001, p=0.88); median length of stay in the hospital (36.8d for AT+ vs. 49.8d for No AT, p=0.91) or intensive care unit (25.3d for AT+ vs. 34.1d for No AT, p=0.63), or adjusted relative risk for in-hospital mortality (0.6; 95% CI, 0.2–1.5). CONCLUSIONS: Intermittent, on-demand dosing of AT concentrate in pediatric patients on ECMO for respiratory failure increased AT levels, but not typically to the targeted level. Following doses with a measurable AT level, the majority of AT levels fell to <80% by 6.8 hrs. The UFH rate remained lower than before the AT dose for > 12 hours. However, in this retrospective study, no differences were noted in the measured clinical endpoints. A prospective randomized study of this intervention may require different dosing strategies; such a study is warranted given the variable use of this costly product across institutions. Disclosures: Off Label Use: Antithrombin concentrate. Gernsheimer:Amgen: Consultancy, Honoraria; Symphogen: Consultancy; Laboratorios Raffo SA: Honoraria; Clinical Options: Consultancy; Hemedicus Corporation: Honoraria; Glaxo Smith Kline Corporation: Consultancy; Shionogi Corporation: Research Funding; Cangene Corporation: Consultancy.
17
Peeters, M., E. Van Cutsem, J. Berlin, J. R. Hecht, R. Ruiz, L. Navale, R. Amado, and N. J. Meropol. "Safety of panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), in patients (pts) with metastatic colorectal cancer (mCRC) across clinical trials." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4138. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4138.
Анотація:
4138 Background: Panitumumab is indicated in pts with EGFr-expressing mCRC refractory to chemotherapy. We present a summary of safety with panitumumab monotherapy in mCRC pts across 10 clinical trials. Methods: Data were pooled from pts enrolled in 10 clinical trials (including 2 extension studies). Pts received at least 1 dose of panitumumab at 2.5 mg/kg QW, 6 mg/kg Q2W, or 9 mg/kg Q3W. Adverse events were graded using NCI-CTC or CTCAE criteria. Results: A total of 920 mCRC pts were included in this analysis: 60% were male; 88% were white; median age (range) was 61 (20, 88) years. All pts had prior therapy; 77% had failed prior fluoropyrimidine, irinotecan, and/or oxaliplatin. Most (80%) pts received panitumumab 6 mg/kg Q2W; 17% and 3% of pts received panitumumab 2.5 mg/kg QW and 9 mg/kg Q3W, respectively. Median (range) follow-up time was 21 (1–124) weeks. A total of 7264 panitumumab infusions were administered with a median (range) of 5 (1–94) infusions/pt. Treatment-related adverse events (AE) were experienced by 94% (grade = 3, 20%) of pts. All pts had = 1 AE. The most common AEs were skin-related and GI toxicities ( table ). Skin-related AEs resulted in discontinuation in 2% of pts. Overall, 12% of pts discontinued panitumumab due to toxicity. Four (0.4%) pts had grade = 3 infusion reactions. In pts with postdose samples (n = 613), increased and persistent postdose levels of anti-panitumumab antibodies were detected in 0.5% of pts by ELISA and in 4.6% of pts by Biacore assay. Conclusions: Skin toxicity was common, but rarely treatment-limiting. Most AEs were mild to moderate and infrequently resulted in discontinuation. Infusion reactions and formation of anti-panitumumab antibodies were rare. The safety profile of 9 mg/kg Q3W panitumumab appeared consistent with other dosages; however, because of the small pt size further evaluation is needed. Panitumumab at 2.5 mg/kg QW and 6 mg/kg Q2W was well tolerated across 10 clinical studies. [Table: see text] No significant financial relationships to disclose.
18
Kim, Dong-Wan, Myung-Ju Ahn, Yuankai Shi, Tommaso Martino De Pas, Pan-Chyr Yang, Gregory J. Riely, Lucio Crinò, et al. "Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 7533. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7533.
Анотація:
7533 Background: Approximately 3–5% of NSCLC harbors ALK gene rearrangements. Crizotinib is a first-in-class, oral, small-molecule competitive ALK inhibitor with anti-MET activity. Methods: PROFILE 1005 is an ongoing global, multicenter, open-label, single-arm, phase II study evaluating the safety and efficacy of crizotinib (250 mg BID in 3-week cycles) in patients with advanced ALK-positive NSCLC who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease. Tumor response was evaluated by RECIST 1.1 every 6 weeks. Patient-reported symptoms and global quality of life (QOL) were assessed using the EORTC QLQ-C30 and LC-13 at baseline, day 1 each cycle and at end of treatment. Results: As of June 2011, 439 patients were evaluable for safety and 255 patients for tumor response. Median age was 53 years. The majority of patients were female (53%), never smokers (65%), and had adenocarcinoma (92%), ECOG PS 0–1 (83%) and ≥2 prior chemotherapy regimens (85%). Among patients evaluable for efficacy, median treatment duration was 25 weeks (77% of patients still ongoing). ORR was 53% (95% CI: 47–60), disease control rate at 12 weeks was 85% (95% CI: 80–89), median duration of response was 43 weeks (96% CI 36–50) and median PFS was 8.5 months (95% CI: 6.2–9.9). The most frequent treatment-related AEs were visual effects (50%), nausea (46%), vomiting (39%), and diarrhea (35%), mostly grade 1–2. 29 patients (6.6%) had treatment-related SAEs, including dyspnea and pneumonitis (4 patients each; 0.9%), and febrile neutropenia and renal cyst (2 patients each; 0.5%). A statistically significant (p<0.05) and clinically meaningful (≥ 10 points) improvement from baseline was observed for patient-reported overall pain, pain in chest, cough, dyspnea, insomnia, fatigue and global QOL. Conclusions: Crizotinib demonstrated a high response rate and PFS, favorable tolerability profile and improvement in patient-reported symptoms. These results provide strong evidence for crizotinib as a standard of care for advanced ALK-positive NSCLC.
19
Sato, Yozo, Hideyuki Nishiofuku, Taku Yasumoto, Atsuhiro Nakatsuka, Kunihiro Matsuo, Yoshihisa Kodama, Daisuke Abo, et al. "Phase II trial of sorafenib combined with on-demand transarterial chemoembolization for advanced stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C): STAB study." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e15648-e15648. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15648.
Анотація:
e15648 Background: Sorafenib has been acknowledged as a standard treatment for advanced stage hepatocellular carcinoma (HCC). This study was conducted to evaluate the safety and efficacy of combination therapy of sorafenib and on-demand transarterial chemoembolization (TACE) for advanced stage HCC. Methods: Inclusion criteria were advanced stage HCC (Barcelona Clinic Liver Cancer stage C), a systemic chemotherapy native status, an Eastern Cooperative Oncology Group performance status 0–1, and a Child-Pugh grade-A. Sorafenib therapy (800 mg daily) was started 4–28 days after TACE. On-demand TACE was allowed. The primary endpoint was the completion rate of protocol treatment, which was defined as sorafenib administration at least for 2 months from initial TACE. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Results: From July 2013 to September 2015, a total of 32 patients were registered from 9 institutions, but one patient was excluded because his tumor turned out to be combined hepatocellular carcinoma and cholangiocarcinoma. The protocol treatment was completed in 28 of 31 enrolled patients (90.3%, 28/31). The median treatment duration was 7.0 months (range 0.5–30) with the median number of TACE was 1 (range 1–4) and the median sorafenib dosage of 400 mg daily (range 154-800). The ORR and DCR were 77% and 90%, respectively. Median OS and PFS were 17.3 months [95% confidence interval (CI), 11.9–22.6] and 5.4 months (95% CI, 4.6–6.2), respectively. The most common grade-3 or -4 adverse events were increased aspartate aminotransferase (55%, 17/31), increased alanine aminotransferase (45% 14/31), and hypertension (23%, 7/31). Conclusions: Combination therapy of sorafenib and on-demand TACE was well tolerated and safe. Furthermore, this combination treatment may provide a survival benefit to patients with advanced stage HCC. Clinical trial information: UMIN000014213.
20
Zatla, Amina Tabet, Imane Mami, Mohammed El Amine Dib, and Mohammed El Amine Sifi. "Efficacy of Essential Oil and Hydrosol Extract of Marrubium vulgare on Fungi Responsible for Apples Rot." Anti-Infective Agents 18, no. 3 (September 11, 2020): 285–93. http://dx.doi.org/10.2174/2211352517666190618105332.
Анотація:
Background: The microorganisms such as Penicillium expansum and Botrytis cinerea are wellknown pathogens in apples during postharvest. So, to protect apples from these pathogens, chemical control methods were exercised. Introduction: The main objective of this work was to study the chemical composition and the in-vitro and in-vivo antifungal properties of essential oil and hydrosol extract of Marrubium vulgare. Methods: In this work, the air-dried aerial parts of Marrubium vulgare were hydrodistilled in a Clevengertype apparatus. The essential oil and hydrosol extract isolated were analyzed using Gas Chromatography (GC) and Mass Spectrometry (GC/MS). The in-vitro antifungal activity of the both extracts was investigated against Botrytis cinerea, Penicillium expansum and Alternaria alternata fungi using radial growth technique. The effect of the essential oil and hydrosol extract on disease development of apple caused by Penicillium expansum in the in-vivo conditions was assessed. Results: The essential oil of Marrubium vulgare was characterized principally by E-β-caryophyllene (23.5%), E-β-farnesene (21%), α-humulene (14.8%), β-bisabolene (11.1%), caryophyllene oxide (6.8%) and phytol (3.1%). While, the methyl-eugenol (65.5%), α-Bisabolol (12.5%), linalool (6.5%) and caryophyllene oxide (6.2%) were the major compounds of hydrosol extract. The result of in-vitro antifungal activity of hydrosol extract showed an interesting antifungal inhibition against Botrytis cinerea, Penicillium expansum and Alternaria alternata with percentage inhibition ranging from 77% to 89% at low concentration of 0.15 mL/L. The essential oil was found to inhibit the growth of Penicillium expansum in a dose-dependent manner, with a percentage inhibition of 100% at 30 mL/L. Furthermore, essential oil and hydrosol extract have demonstrated promising in-vivo antifungal activity to control infection of apples by Penicillium expansum up to 25th day of storage, compared with the control. Conclusion: The preventive and protective effects of essential oil and hydrosol extract could be exploited as an ideal alternative to synthetic fungicides for using the protection of stored apples from fungal phytopathogens.
21
Oran, B., A. Aleman, E. J. Shpall, C. Hosing, M. Korbling, P. Anderlini, R. Champlin, and M. Donato. "Higher Rate of Thrombotic Thrombocytopenic Pupura (TTP) Associated with Graft Versus Host Disease (GVHD) and Unrelated Donor Bone Marrow Transplantation (BMT)." Blood 106, no. 11 (November 16, 2005): 1111. http://dx.doi.org/10.1182/blood.v106.11.1111.1111.
Анотація:
Abstract TTP is one of the complications of allogeneic hematopoietic stem cell transplantation (HSCT). In contrast to idiopathic cases, post-transplantation TTP may not be associated with severe von Willebrand factor-cleaving protease deficiency but rather a diffuse endothelial injury. Our aim was to define incidence, risk factors and mortality of TTP following allogeneic HSCT. 1312 patients with lymphoid malignancies (n=605), myeloid malignancies (n=688) or aplastic anemia (AA, n=18) who were treated with ablative preparative regimens (n=614) or reduced intensity regimens (n=697) followed by HSCT from an HLA matched related (MRD, n=694) or unrelated donor (MUD; n=461) and 1–3 antigen mismatched related (MMR, n=99) or unrelated donor (MMUD, n=57) between December 1997 and December 2004 were studied. Patients with prior allogeneic HSCT or graft failure were excluded. GVHD prophylaxis was tacrolimus-based in 1276 (97.3%) and cyclosporine based in 15 (1.1%) patients. Twenty patients did not receive GVHD prophylaxis per protocol. Anti-thymocyte-globulin (ATG) was added in 350 patients. Stem cell sources were bone marrow (n=626), peripheral blood (n=635) or cord blood (n=50). The following variables were evaluated: age, gender, primary diagnosis, disease status before HSCT, intensity of preparative regimen, stem cell source and acute GVHD(aGVHD) grade ≥2 (time dependent variable). Of the 1312 patients with a median follow-up from transplantation of 11.4 months (range, 5 days-7.2 years), 77 developed TTP (6%). The actuarial risk of developing TTP was 6.5% at 1 year. The median time of the onset of TTP was 67 days post HSCT (range, 11–1812) with 27 cases (35%) presenting after day 100. Female gender, lymphoid malignancies, unrelated or antigen mismatched related donor and aGVHD grade ≥2 were found to be independent risk factors. (Table1). Among the patients who had aGVHD grade≥2, the median time of interval between the onsets of two events was 25 days (range, 2–335 days). All patients were treated with therapeutic plasma exchange (PE). Of the 77 patients only 1 died of TTP (intracranial hemorrhage). The overall one-year survival after TTP was 29% and the most common cause of death were acute or chronic GVHD (n=35, 55%) and primary disease progression (n=10, 16%). Stem cell donors other than MRD, lymphoid malignancies and aGVHD≥2 have been established as risk factors associated with development of TTP and therapeutic PE has been shown to decrease TTP related mortality. Risk factors for TTP after allogeneic HSCT Variables sample size events HR 95% CI p Male 793 33 1.0 Female 518 44 2.2 1.3–3.6 0.002 Myleoid malignancy 688 33 1.0 Lymphoid malignancy 605 42 1.9 1.1–3.3 0.03 AA 18 2 1.3 0.2–8.0 0.75 MRD 694 28 1.0 MUD 461 40 2.9 1.6–5.1 <0.001 MMR 99 7 2.4 0.9–6.0 0.06 MMUD 57 2 1.7 0.4–7.6 0.5 aGVHD ≥2 370 39 3.3 2.0–5.5 <0.001
22
Alexiu, C., L. Krebs, C. Villa-Roel, B. R. Holroyd, M. Ospina, C. Pryce, J. Bakal, et al. "MP12: Acute asthma presentations to emergency departments in Alberta: an epidemiological analysis of presentations." CJEM 19, S1 (May 2017): S69. http://dx.doi.org/10.1017/cem.2017.178.
Анотація:
Introduction: Asthma is a chronic condition and exacerbations are a common reason for emergency department (ED) presentations across Canada. The objective of this study was to characterize and describe acute asthma presentations over a five-year period. Methods: Administrative health data for Alberta from 2011-2015 was obtained from the National Ambulatory Care Reporting System (NACRS) for all adult (>17 years) acute asthma (ICD-10-CA: J45) ED presentations. All presentations to an Alberta ED with a primary or secondary diagnosis of acute asthma were eligible for inclusion. Presentations with a Canadian Triage and Acuity Scale (CTAS) score of 1 were excluded. Data from NACRS were linked with a provincial diagnostic imaging database. Data are reported as means and standard deviation (SD), medians and interquartile range (IQR) or proportions, as appropriate. Results: From 2011-2015, a total of 51,269 (~10,000/year) acute asthma presentations were made by 34,481 patients (~0.3 presentations per patient per year). The median age was 35 years (IQR: 25, 49 years) and more patients were female (57.2%). Few patients arrived to the ED by ambulance (6.5%) and the most frequent CTAS score was 3 (43.5%). The majority of these patients (77%) had a primary diagnosis of asthma in the ED. Differences were explored between those with a primary asthma diagnosis and those with a secondary diagnosis (e.g., ambulance arrival, length of stay, hospital admission, etc.). Although differences were statistically significant, no clinically relevant differences were identified. Patients with asthma most frequently had a co-diagnosis of acute upper respiratory infection (6.2%); other co-diagnoses included bronchitis (4.7%), pneumonia (3.7%), heart failure (0.18%), pulmonary embolism (0.15%), and pneumothorax (0.03%). For 39.3% of patients, ED management included chest x-ray. The majority of patients were discharged from the ED (92.2%) following a median length of stay of 2.2 hours (IQR: 1.2, 3.8 hours). Conclusion: Acute asthma remains an important ED presentation in Alberta and the absolute frequency of presentations has remained relatively stable over the past five years. Frequency of chest x-ray ordering is high and represents a target for future interventions to reduce ionizing radiation exposure, improve patient flow and reduce healthcare costs.
23
Gunturkun, Fatma, Robert L. Davis, Gregory T. Armstrong, John L. Jefferies, Kirsten K. Ness, Daniel M. Green, John Thomas Lucas, et al. "Deep learning for improved prediction of late-onset cardiomyopathy among childhood cancer survivors: A report from the St. Jude Lifetime Cohort (SJLIFE)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 10545. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.10545.
Анотація:
10545 Background: Early identification of survivors at high risk for treatment-induced cardiomyopathy may allow for prevention and/or early intervention. We utilized deep learning methods using COG guideline-recommended baseline electrocardiography (ECG) to improve prediction of future cardiomyopathy. Methods: SJLIFE is a cohort of 5-year clinically assessed childhood cancer survivors including baseline ECG measurements. Development of cardiomyopathy was identified from clinical and echocardiographic measurement using CTCAE criteria (grade 3-4). We applied deep learning approaches to ECG, treatment exposure and demographic data obtained at baseline SJLIFE assessment. We trained a cascaded model combining a 12-layer 1D convolutional neural network to extract features from waveform ECG signals with a 2-layer dense neural network to embed features from other phenotypic data in tabular format to determine if use of deep learning with ECG data could improve prediction of cardiomyopathy. Results: Among 1,218 subjects (median age 31.7 years, range 18.4-66.4) without cardiomyopathy at baseline evaluation, 616 (51%) were male, 1,041 (85%) white, 157 (13%) African American and 792 (65%) were survivors of lymphoma/leukemia. Follow-up averaged 5 (0.5 to 9) years from baseline examination. Mean chest radiation dose was 1350 cGy (range 0 to 6,200 cGy) and mean cumulative anthracycline dose was 191 mg/m2 (range o to 734 mg/m2). A total of 114 (9.4%) survivors developed cardiomyopathy after baseline. A cascaded deep learning model built on a training set (N = 974 participants) classified cardiomyopathy in the test set (N = 244 participants) using both clinical and ECG data with a sensitivity of 70%, specificity of 73%, and AUC of 0.74 (95% CI 0.63-0.85), compared to a model using clinical data alone (sensitivity 61%, specificity 62%, and AUC 0.67, 95% CI 0.56-0.79). In subgroup analyses, models predicting cardiomyopathy within 0-4 years following baseline had a sensitivity, specificity, and AUC of 77%, 78%, and 0.78 (0.65-0.91), respectively. When predicting cardiomyopathy 5-9 years following baseline, model performance dropped to a sensitivity, specificity, and AUC of 70%, 70%, and 0.68 (0.50-0.87), respectively. Conclusions: Deep learning using ECG at baseline evaluation significantly improved prediction of cardiomyopathy in childhood cancer survivors at high risk for cardiomyopathy. Future directions will incorporate deep learning approaches to echocardiography to further improve prediction.
24
Assandri, R., G. Martellosio, and A. Montanelli. "AB0051 SERUM AMYLOID A AND PENTRAXIN 3: INNATE IMMUNE RESPONSE AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1328.1–1328. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1933.
Анотація:
Background:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that involves several molecular patterns with a wide spectrum of clinical manifestations and symptoms. Inflammation and related pathway play a role in SLE pathogenesis. The pentraxin superfamily including long and short pentraxin, C Reactive Protein CRP, Serum amyloid A (SAA), Pentraxin 3 (PTX3) are key components of innate immune system and induce a variety of inflammation associated pathway. However Literature provides several evidences that CRP serum levels not correlated with clinical and immunological manifestations. This situation affected clinical practice and the patient follow up. PTX3 have been identified as a component of inflammatory status in several autoimmune conditions. SAA is an acute phase protein secreted in large quantity during inflammation.Objectives:We want to evaluated SAA, PTX3 and CRP concentrations, their correlation between SLE Disease Activity Index (SLEDAI), that including complement fractions C3, C4.Methods:We enrolled fifty patients that fulfilled the SLE American College of Rheumatology criteria and fifty healthy subjects. The SLE disease activity was classified with the SLEDAI (0 to 12). Patients were divided into two groups according to SLEDAI score: inactive group (Group 1, 25 patients, 50%: SLEDAI < 4) and active group (Group 2, 25 patients, 50%: SLEDAI 5 to 12). PTX3 concentration was measured by a sandwich ELISA kit (Hycult) with 2.8 ng/mL cut-off point. SAA concentration was detected by nephelometry performed on a BN ProSpec System (Siemens, Germany), with assay kit based on polyclonal antibodies (Siemens Healthcare Diagnostics Products, Germany, 6.5 mg/L cut-off point). High sensitive CRP concentrations were determined using the ci8200 platform (Abbott Laboratories Chicago, Illinois).Results:Plasma PTX3 and serum SAA levels was significantly higher in SLE patients than in the healthy subjects (PTX311.5 ± 7.3 ng/mL vs 2.3 ± 1.1; p < 0.001; SAA: 87 ±77 mg/L vs 2.6±2.5; p < 0.001). These differences were not evident in CRP levels (8.5 ± 7.8 mg/L vs 6.2± 2.5). Considering two groups, there were statistical differences in PTX3 level (Group 2: 14.9 ± 12 ng/mL vs Group 1: 2.16 ±0.5 ng/mL, p<0,05) and SAA concentration (Group 2: 114 ± 89 ng/mL vs Group 1: 3.6 ±1.7 ng/mL, p<0,05) but not in CRP concentration (Group 2: 11.5 ± 8.4 mg/L vs Group 1: 9.5 ±3.5). There was a significantly negative correlation between C3, C4 fractions, PTX3 and SSA levels (respectively r = −0.74, p=<0.05, and r = −0.79, p<0.05). No statistical correlation were appeared between C3, C4 fractions and CRP serum levels (r= −0,12., p= 0.82, and r= −0.18, p= 0,21). We noted a positive significant correlation between SLEDAI, PTX3 and SAA concentration (r = 0.79, p < 0.05, 0.83, p < 0.05, respectively) an increase in PTX3 and SAA levels followed the lupus flare and symptoms. No significant correlation appeared between SLEDAI and CRP (r= 0.15, p=0.89)Conclusion:PTX3 and SAA concentration was significantly higher in SLE patients than the healthy control subjects and their levels reflected disease activity. We showed a direct correlation between PTX3 and SAA. In SLE patients PTX3 and SAA concentrations were correlated with SLEDAI. We suggest an integrate viewpoint in witch SAA and PTX3 may play a role as a biomarker of disease activity, with synergic work during SLE events. Evidences suggested that PTX3 and SAA could trigger the same molecular pathway, by TLR4, via NF-kB.References:[1]Assandri R, Monari M Montanelli A. Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved, Translational Biomedicine (2015)Disclosure of Interests:None declared
25
Veldhuis, J. D., M. Bidlingmaier, S. M. Anderson, W. S. Evans, Z. Wu, and C. J. Strasburger. "Impact of Experimental Blockade of Peripheral Growth Hormone (GH) Receptors on the Kinetics of Endogenous and Exogenous GH Removal in Healthy Women and Men." Journal of Clinical Endocrinology & Metabolism 87, no. 12 (December 1, 2002): 5737–45. http://dx.doi.org/10.1210/jc.2001-011885.
Анотація:
Abstract Organs that respond to and metabolize GH are enriched in cognate high-affinity receptors. However, whether isologous receptors mediate the de facto access of ligand to cellular degradative pathways is not known. To address this query, we assessed the distribution and whole-body elimination kinetics of (endogenous and exogenous) GH before and after administration of a novel, potent, and selective recombinant human (rh) GH receptor antagonist peptide, pegvisomant. Sixteen healthy young adults (nine men and seven women) participated in a double-blind, prospectively randomized, within-subject cross-over study. The intervention comprised a single sc injection of placebo vs. a high dose of pegvisomant (1 mg/kg sc) timed 62 and 74 h before the overnight sampling and daytime infusion sessions, respectively. The half-life, metabolic clearance rate (MCR), and distribution volume of GH were quantitated by way of: 1) deconvolution analysis of serum GH concentration time series collected every 10 min for 10 h; 2) exponential regression analysis of the decay of GH concentrations after a 6-min iv pulse of rhGH (1 and 10 μg/kg); 3) calculation of the MCR during constant iv infusion of rhGH (0.5 and 5.0 μg/kg every 2 h); and 4) exponential fitting of the elimination time-course of GH concentrations following cessation of each constant infusion. Concentrations of GH and pegvisomant were measured in separate, noncross-reactive, two-site monoclonal, immunofluorometric assays. Pegvisomant concentrations averaged 4860 ± 480 μg/liter (±sem) across the infusion interval, thus exceeding low steady state GH concentrations by 3000-fold. Inhibitory efficacy of the GH receptor antagonist peptide was affirmed by way of a 34% reduction in the serum total IGF-I concentration, i.e., from 257 ± 37 (placebo) to 170 ± 24 (drug) μg/liter (P < 0.001); and a reciprocal 77% elevation of the (10-h) mean GH concentration, i.e., from 1.3 ± 0.23 (placebo) to 2.3 ± 0.42 (drug) μg/liter (P = 0.003). ANOVA disclosed that prior administration of pegvisomant (compared with placebo) did not alter: 1) the calculated half-life (minutes) of secreted GH, which averaged 15 ± 1.3 (placebo) and 14 ± 0.69 (drug); 2) the half-time of disappearance (minutes) of an iv pulse of rhGH, 15 ± 1.0 (placebo) and 13 ± 0.5 (drug) (for the 10 μg/kg dose); 3) the distribution volume (milliliters per kilogram) of rhGH, 59 ± 6.2 (placebo) and 58 ± 3.5 (drug); 4) the steady state GH concentration (micrograms per liter) attained during constant iv infusion of rhGH (at a rate of 5 μg/kg every 2 h), 18.2 ± 2.4 (placebo) and 18.3 ± 2.3 (drug); 5) the half-life (minutes) of elimination of GH from equilibrium, 16 ± 0.98 (placebo) and 16 ± 1.8 (drug); and 6) the steady state MCR (liters per kilogram per day) of rhGH, 3.8 ± 0.32 (placebo) and 3.5 ± 0.31 (drug). In ensemble, the present data refute the a priori postulate that vascular-accessible GH receptors determine the in vivo pseudoequilibrium kinetics of GH disappearance in the human.
26
Bicchi, Amelia Guzman, Antonio E. Lubrano Heinsen, Joaquin Gomez-Daspet, and John Tourtelot. "Diabetic Myonecrosis: A Rare Condition That Present With Pain." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A378. http://dx.doi.org/10.1210/jendso/bvab048.770.
Анотація:
Abstract Diabetic myonecrosis is the term used for spontaneous ischemic necrosis of skeletal muscle, unrelated to atheroembolism or occlusion of major arteries. This is an uncommon manifestation of long-standing and poorly controlled diabetes mellitus. A 65-year-old Hispanic female presented to the Hospital with one-week history of worsening right thigh pain. She denied associated fever, trauma, history of blood clots, past surgery, recent travel, ect. Patient has history of uncontrolled diabetes type 2, diabetic neuropathy and End-Stage Kidney Disease on hemodialysis for the last 3 years. Home medications include gabapentin 300 mg daily and insulin 70/30 20 units twice a day. On physical exam, vital signs appeared within normal limits. There was right medial and anterior thigh fullness, warmth and tenderness without erythema or fluctuance. Laboratory studies are pertinent for HbA1C 8.8% (n <6.5%), C-reactive protein (CRP) 12.97 (n <0.5 mg/dL), Erythrocyte sedimentary rate (ESR) >130 (n 0–30 mm/hr), Creatinine: 6.2 (n 0.57–1.11 mg/dL), BUN 77 (n 6–20 mg/dL), CO2 19 (n 22–29 mEq/L) and albumin 2.7(n 3.5–5.0 gm/dL). Other labs including CPK, glucose, ANA panel and CBC are within normal limits. Patient was admitted with initial diagnosis of cellulitis without improvement in clinical status after 3 days of antibiotics. MRI of the right thigh showed proximal thigh muscle, cutaneous and subcutaneous edema. Right thigh muscle biopsy showed marked myonecrosis with surrounding endomysial edema, foci of histiocytes, fibroblasts, and regenerating muscle fibers. Histologic features, together with localized muscle pain, normal CPK, negative microbiologic studies and uncontrolled diabetes are consistent with diabetic myonecrosis. Insulin was adjusted for tight glucose control and patient was started on low dose aspirin with outpatient follow-up. Diabetic myonecrosis presents with acute onset of painful swelling that evolves over days or weeks. The most common affected areas are the front and back of the thigh and calf. The pathophysiology is not well understood but appears related to thromboembolic events secondary to microvascular endothelial damage leading to tissue ischemia, which triggers an inflammatory cascade causing local tissue damage and ischemic necrosis. Common laboratory findings include elevated ESR, CRP and HbA1C level. Treatment involves symptomatic management, rest, glycemic control, analgesia and low-dose aspirin. The optimal approach is uncertain and current treatment is based upon published case reports and case series; there have been no randomized trials to compare approaches or specific agents. Close patient follow-up and tight glycemic control are key elements to prevent progression of this condition.
27
Vogel, Michael, Heiko Stern, and Konrad Bühlmeyer. "Interobserver variability of determination of the size of the left-to-right shunt in isolated atrial septal defects within the oval fossa by Doppler and cross-sectional echocardiography." Cardiology in the Young 2, no. 1 (January 1992): 35–41. http://dx.doi.org/10.1017/s1047951100000561.
Анотація:
SummaryAlthough noninvasive estimation of the ratio of pulmonary to systemic flow by measuring the cross-sectional areas of the pulmonary and aortic valves and the respective time integrals of the velocity of blood is widely used to determine the amount of shunting in patients with left-to-right shunts, few data exist concerning interobserver variability. We assessed such variability of shunt calculations derived from Doppler echocardiography in 10 children aged six (3.5–11) years with an isolated atrial septal defect within the oval fossa. The ratio of flows was calculated by measuring stroke volumes over the pulmonary trunk and the aorta immediately before and at an average of seven days (5–11) following surgical closure of the atrial septal defect. Two independent observers measured the cross-sectional areas of the aortic and pulmonary orifices and the velocity time integrals and calculated the size of the shunt from these data. All measurements were performed five times, and the mean of these five measurements was calculated and compared for analysis. Before surgery, observer I had measured a ratio of pulmonary to systemic flow of 3.8 (2.1–6.2) and observer II of 3.5 (1.9–5). The mean interobserver difference in terms of the size of the shunt was 1.1 (or 30%). After surgery, observer I measured a ratio of 1.3 (0.8–1.7) and observer II of 1.1 (0.7–1.6). The cross-sectional area of the pulmonary valve was measured as 3.6 (2.6–4.9) cm2 and 3.4 (2.3–5.8) cm2 respectively, with a mean interobserver difference of 0.8 cm2 or 23%. For the velocity time integrals across the pulmonary trunk, the mean interobserver difference was 13% (4–38) before and 16% (0–55) after surgery. The respective variability for the aortic velocity time integrals was 11 % (4–46) before and 9% (0.5–23) after surgery. The variability of measurements of maximal flow velocity across the pulmonary trunk was 15% (4–38) before and 18% (1–77) after surgery. The respective variability for the aortic flow velocity was 11 % (2–28) before and 9% (4–23) after surgery. A paired t-test showed no significant differences for all parameters assessed. The difficulty of reproducing measurements of the pulmonary valve is an important factor affecting interobserver variability. The magnitude of interobserver difference was significantly related to the cross-sectional area of the pulmonary trunk (r=0.84; p<0.02). The interobserver variability may be considerable, and is large enough to influence clinical decisions. Thus, we conclude that a decision regarding need for surgery cannot be based solely on calculation of the shunt derived only from Doppler measurements in patients with isolated atrial septal defects within the oval fossa.
28
Maassen, J. M., S. A. Bergstra, P. D. de Buck, M. van Oosterhout, T. Huizinga, and C. Allaart. "POS0479 THE IMPACT OF FLARES ON PATIENT REPORTED OUTCOMES IN RHEUMATOID AND UNDIFFERENTIATED ARTHRITIS PATIENTS – A SUB-ANALYSIS OF THE IMPROVED STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 471.2–472. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2656.
Анотація:
Background:In rheumatoid arthritis (RA) patients in low disease activity, flares are associated with symptom deterioration. Patients in clinical remission may flare but still have low disease activity. How does this affect patient reported outcomes?Objectives:To evaluate the prevalence of disease flares in patients treated to target drug free remission, and to study the impact of disease flares on patient-reported outcomes (PROs) for flares with different impact on disease activity.Methods:In the IMPROVED study 610 patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated to target drug free remission (DAS <1.6) for 5 years. As soon as DAS was <1.6, treatment was tapered to discontinuation. Patients with at least 8 months follow-up were selected. A flare was defined according to three definitions; A) DAS ≥1.6 and ≥0.6 increase from the previous visit regardless of the previous DAS; B) minor flare from remission; a DAS ≥1.6 with <0.6 increase and previous DAS <1.6; C) major flare from remission; a DAS ≥1.6 with ≥0.6 increase and previous DAS <1.6. Linear mixed models were used to compare functional ability, measured by the health assessment questionnaire (HAQ), at visits where a flare occurred versus visits without a flare. Fisher’s exact test were used to compare percentages with ≥0.22 HAQ increases between groups with and without LDA at the moment of flare. A generalized linear mixed model was used to calculate the odds ratio for a deterioration of ≥20 mm in VAS of PROs global health (GH), disease activity, pain and morning stiffness (from the preceding visit) during a flare.Results:Of the 585 patients with sufficient follow-up, 75% experienced a flare A, 26% a flare B, and 68% a flare C, at least once. Most flares were observed after t=8 and t=12 months. In 55%, 100%, and 69% of visits with a flare A, B or C, the patients were still in LDA (DAS=<2.4). In 55% of the visits where a flare was associated with a DAS increase ≥0.6 (flare A & C) there was also clinically relevant increase in HAQ of ≥0.22. The mean difference in HAQ was 0.27 with flare A (p<0.01), 0.03 with flare B (p=0.72) and 0.18 with flare C (p<0.01). If was DAS >2.4 (LDA) at the moment of flare, HAQ increased ≥0.22 in 68% of all flares A, and 77% of all flares C (p-values <0.01, compared to flares where patients were still in LDA, DAS=<2.4). The odds ratios of a >20 mm deterioration in VAS global health, VAS disease activity, VAS pain and VAS morning stiffness was significant ≥1 for flares with a ≥0.6 increase in DAS (flares A and C), and ≤1 for minor flares (B) (table 1).Conclusion:In early arthritis patients, during 5 years treated to target drug free DAS-remission, disease flares with loss of DAS-remission were common. Although the majority of patients who flared were still in LDA, most reported more pain, morning stiffness, increased disease activity and a diminished global health. On average, deterioration in HAQ only exceeded the minimum clinically important difference (delta HAQ >=0.22) in case of a ≥0.6 increase in DAS, independent of the previous DAS. Depending on the definition of flare, up to 45% of patients lost DAS LDA, and in this group the functional deterioration significantly more often exceeded the MCID as compared to the patients that flared but were still in LDA. More research is needed to find out which patients are most at risk for clinically relevant flares, and to evaluate the impact of flares in patients with remission on long term outcomes.Table 1.Odds Ratios and 95% confidence intervals for > 20 mm increase in PROs on 100mm visual analogue scalesFlare AFlare B (minor)Flare C (major)Prevalence ≥20 mmaOR(95% CI)Prevalence ≥20 mmaOR(95% CI)Prevalence ≥20 mmaOR(95% CI)Global health62%2.1 (1.5; 2.8)45%0.5 (0.4; 0.7)62%1.4 (1.1; 1.8)Disease activity62%2.5 (1.7; 3.8)45%0.4 (0.3; 0.6)62%2.1 (1.4; 3.0)Pain87%2.0 (1.3; 3.1)78%0.5 (0.3; 0.8)87%1.8 (1.2; 2.5)Morning stiffness84%1.7 (1.1; 2.6)77%0.6 (0.4; 0.9)86%2.1 (1.5; 2.9)a The prevalence of >20 mm deterioration in VAS PRO’s during a visit with a flare.Acknowledgements:We would like to thank all patients for their contribution as well as the rheumatologists who participated in the IMPROVED-study group. We would also like to thank all other rheumatologists and trainee rheumatologists who enrolled patients in these studies, and all research nurses for their contributions.Disclosure of Interests:Johanna M. Maassen: None declared, Sytske Anne Bergstra: None declared, Petronella DM de Buck: None declared, M. van Oosterhout: None declared, Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: the IMPROVED study was designed by the investigators and financially supported by AbbVie in the first year.
29
Tillett, W., V. Navarro-Compán, N. Booth, T. Holzkaemper, J. Hill, E. Lubrano, and T. Truer. "AB0548 EFFECTIVENESS OF IXEKIZUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM A REAL-WORLD EUROPEAN SURVEY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1307–8. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2001.
Анотація:
Background:Limited real world (RW) data are available for IL-17A blocker ixekizumab (Ixe), approved for psoriatic arthritis (PsA) in EU Feb 2018.Objectives:Describe RW outcomes for PsA patients (pts) receiving Ixe.Methods:Cross-sectional, observational study of PsA pts treated with Ixe in the 2020 Adelphi PsA Plus Program (FR, DE, ES & UK). Rheumatologists recruited the first 6 consecutive consulting Ixe pts and provided demographics, PsA manifestations, clinical measures (66 swollen joint count (SJC), 68 tender joint count (TJC), psoriasis area and severity index [PASI], body surface area [BSA] affected by psoriasis [PsO]), rheumatologist-recorded pt measures (skin/joint pain & fatigue [0-10 numeric rating scales (NRS)], health assessment questionnaire [HAQ-DI]) & prescribed dose. All outcomes recorded for pts with scores available at Ixe initiation (II) & at last assessment (LA).Results:124 rheumatologists provided data for 698 Ixe pts, mean age 49 years (19-79), 48% female, mean BMI 27 (18-44), 56% dermatologist co-managed and mean time diagnosed 6 years (0-35). At Ixe initiation, 78% of pts with known BSA had concomitant mod-sev-PsO defined as BSA≥10% (mean 19.8, n=428) and mean PASI 26.3 (n=164). The predominant PsA phenotype was polyarthritic in 49% (n=345), mono/oligoarthritic in 30% (n=208), axial in 12% (n=81) and enthesitic in 8% (n=55). Previous treatment before Ixe included ≥1 conventional synthetic DMARD (csDMARD) for 71% of pts. Of bio-experienced pts (57%), 40% had received ≥2 biologics. Mean Ixe treatment duration (n=698) 39.4 weeks (wks, 0-170), of which 575 (82%) had received >12 wks of Ixe. 71% of pts received label recommended dose (80mg every 4wks). 52% pts received csDMARD in combination with Ixe. In the RW, Ixe improved TJC, SJC, joint pain, BSA, fatigue and HAQ-DI, Table 1.Table 1.Outcomes for pts receiving Ixe >12weeks (n=575)OverallBSA ≥10% at Ixe initiationMod-sev-PsO physician judgementPredominant mono/oligo arthritisPredominant polyarthritisWith csDMARDWithout csDMARDBSA, n35627025498184188168mean [SD]Ixe initiation (II)19.8 [14.8]24.7 [13.5]23.1 [13.6]17.4 [15.0]20.9 [15.0]21.8 [15.0]17.4 [14.2]Last Assessment (LA)6.6 [7.5]9.3 [8.7]7.9 [7.9]5.0 [6.0]7.6 [8.4]7.3 [7.9]5.9 [7.1]Mean weeks on Ixe43414150414146TJC*, n125728639725669mean [SD, %<5]II12.2 [10.6, 29]14.4 [11.3, 18]12.9 [11.1, 21]6.4 [8.2, 59]15.4 [10.8, 12]13.0 [9.9, 25]11.5 [11.1, 32]LA4.1 [6.4, 77]5.2 [7.7, 71]3.6 [6.3, 80]1.1 [1.4, 97]6.2 [7.7, 64]3.4 [3.9, 73]4.6 [7.8, 80]SJC*, n1458210244846085mean [SD, %<5]II14.8 [13.5, 33]18.8 [14.4, 22]16.3 [13.8, 26]7.2 [8.5, 68]18.2 [13.6, 12]14.5 [12.0, 37]15.1 [14.8, 31]LA4.8 [8.7, 79]7.0 [10.7, 66]5.1 [9.3, 75]0.9 [1.9, 95]6.6 [9.0, 68]3.1 [7.8, 90]5.9 [9.1, 71]Joint pain (NRS 0-10), n575270349166291294281mean [SD]II6.6 [1.7]6.7 [1.7]6.7 [1.7]6.2 [1.8]7.0 [1.5]6.6 [1.7]6.6 [1.6]LA2.7 [1.9]3.0 [2.1]2.8 [2.0]2.1 [1.6]3.0 [2.1]2.8 [1.9]2.5 [1.9]Fatigue (NRS 0-10), n575270349166291294281mean [SD]II5.4 [2.5]5.8 [2.4]5.7 [2.5]4.7 [2.5]5.7 [2.4]5.7 [2.4]5.1 [2.5]LA2.6 [2.1]2.7 [2.1]2.7 [2.2]2.0 [1.9]2.9 [2.2]2.7 [2.1]2.6 [2.1]HAQ DI, n59414210283128mean [SD, %<0.5]II1.8 [0.7, 5]1.9 [0.6, 0]1.8 [0.7, 2]1.9 [0.7, 10]1.8 [0.8, 7]1.9 [0.6, 3]1.7 [0.8, 7]LA0.8 [0.6, 41]0.8 [0.6, 32]0.8 [0.7, 45]0.7 [0.7, 60]0.7 [0.6, 36]0.7 [0.5, 32]0.7 [0.8, 50]*Additional analysis for pts whose fatigue/joint pain rating improved (from ≥4 at Ixe initiation to ≤3 at LA), their mean TJC was 2.7 & SJC 4.3 at LA for fatigue, TJC 1.7 & SJC 2.7 at LA for joint pain.When BSA was not recorded, physician judgement of PsO severity was used. No imputation of missing data.Conclusion:We report RW outcome data amongst pts treated with Ixe including mono/oligo arthritis and a limited sample of enthesitis and dactylitis pts. Our results are consistent with clinical trial populations across disease domains, including an improvement in joint pain.Disclosure of Interests:William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc. and UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc. and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly & company, Janssen and UCB, Victoria Navarro-Compán Speakers bureau: AbbVie, BMS, Janssen, Eli Lilly & Co, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: AbbVie, BMS, Janssen, Eli Lilly & Co, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: AbbVie, BMS, Janssen, Eli Lilly & Co, MSD, Novartis, Pfizer, Roche and UCB, Nicola Booth: None declared., Thorsten Holzkaemper Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, Julie Hill Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, Ennio Lubrano Speakers bureau: Alfa-Sigma, Abbvie, Galapagos, Janssen Cilag, Lilly., Consultant of: Alfa-Sigma, Abbvie, Galapagos, Janssen Cilag, Lilly., Tamas Truer Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company.
30
Devito, L. G., C. B. Fernandes, H. N. Ferreira, and F. C. Landim-Alvarenga. "71 VITRIFICATION OF BOVINE OOCYTES IN MEDIA WITH GLYCEROL + ETHYLENE GLYCOL BEFORE AND AFTER IN VITRO MATURATION." Reproduction, Fertility and Development 20, no. 1 (2008): 116. http://dx.doi.org/10.1071/rdv20n1ab71.
Анотація:
The cryopreservation process aims to keep the cellular metabolism in a quiescent state for an indeterminate length of time. In mammals, oocyte cryopreservation success is important for the establishment of genetic banks. The objective of the present experiment was to evaluate the effect of vitrification on oocyte meiotic ability and the integrity of the metaphase plate in immature and in vitro-matured bovine oocytes. Bovine cumulus–oocytes complexes (COCs) were harvested from slaughterhouse ovaries and randomly divided into 3 groups: (G1) non-vitrified oocytes subjected to in vitro maturation, (G2) immature oocytes vitrified and then subjected to in vitro maturation after warming, and (G3) in vitro-matured oocytes subjected to vitrification. For in vitro maturation, oocytes were incubated for 22 h in 5% CO2 in air in TCM-199 with fetal calf serum, estradiol, LH, FSH, pyruvate, and gentamicin. For vitrification, the oocytes were exposed to the cryoprotectors in three steps: solution 1 containing 1.4 m glycerol in PBS for five min, and then solution 2 containing 1.4 m glycerol and 3.6 m ethylene glycol in PBS for another five min. After exposure to the second solution, the oocytes were transferred to 30-µL drops of solution 3 containing 3.4 m glycerol and 4.6 m ethylene glycol, loaded (5 oocytes per straw) in less than 1 min into 0.25-mL straws between two columns of 0.5 m galactose in PBS separated by two air bubbles, and immediately set in liquid nitrogen vapor. After 1 min of equilibration in liquid nitrogen vapor, the straws were immersed in liquid nitrogen. Warming was performed by holding the straws for 10 s in air, followed by 10 more s in a water bath at 20–22�C. The straws were then shaken 5 to 8 times to mix the bubbles (movement similar to that for a thermometer) and left horizontally for 6 to 8 min at room temperature. The rates of metaphase II and degeneration were analyzed by ANOVA followed by the Student t-test. The oocytes were stained with 100 µg mL–1 Hoechst 33342 and examined in an inverted microscope equipped with fluorescent light (UV filters 535 and 617 mm). Three different routines were realized with a total of 90 oocytes per group. The metaphase II rates in G1 (48/90, 53.3%) and G3 (42/90, 46.6%) were statistically the same (P e 0.05), but were higher (P d 0.05) than in G2 (0/90, 0%). The degeneration rates were: G1 (18/90, 20%), G2 (77/90, 85.6%), and G3 (7/90, 7.8%). The vitrification procedure damaged mainly the immature oocytes, since in the G2 the degeneration rate was higher and the oocytes were not able to resume meiosis. Meanwhile, when oocytes were vitrified after in vitro maturation, the metaphase II rate was similar to the one observed in IVM oocytes not subjected to vitrification. This indicates that the vitrification procedure performed in this experiment did not damage the structure of the metaphase II plate. However, more studies are necessary to predict the developmental potential of these in vitro-matured oocytes.
31
Abraham, M. C., A. Ruete, and Y. C. B. Brandt. "260 BREED INFLUENCES OUTCOME OF IN VITRO PRODUCTION OF EMBRYOS IN CATTLE." Reproduction, Fertility and Development 22, no. 1 (2010): 287. http://dx.doi.org/10.1071/rdv22n1ab260.
Анотація:
Fertility among cattle breeds can vary. The Swedish Red and White dairy breed (SRB) has been systematically bred for good reproductive traits since 1970 and might therefore have retained a better oocyte quality than other dairy breeds. The aim of this study was to determine if the breed of oocyte donor affects the development of embryos using IVM, IVF, and IVC. Oocyte developmental competence in vitro was compared between the SRB (n = 77 animals), the Swedish Holstein breed (SLB, n = 49), and beef breeds (mixed breeds, n = 97). The oocytes (n = 1380, 18 batches) were aspirated from abattoir-derived ovaries from healthy animals with known identity. Statistical analyses were performed using Student’s t-tests and generalized linear mixed models with random effects. The time of collection in relation to slaughter and time of day, as well as aspiration and the following in vitro procedures, were consistent throughout the experiment. The oocytes were matured, fertilized (frozen semen), and cultured according to conventional protocols without serum. Data are presented as mean ± SEM. The SRB and SLB groups were comparable in age [SRB: 66% cows (over 3 years of age), 27% young cows (calved at least once but not over 3 years of age), and 7% heifers; SLB: 63% cows, 20% young cows, and 17% heifers], carcass classification (scale 1-15, where 15 = highest amount of muscle; SRB: 3.8 ± 0.2, SLB 3.5 ± 0.3), body fat (scale 1-15, where 15 =highest amount of fat; SRB: 8.4 ± 0.4, SLB 8.8 ± 0.5) and kilograms of carcass weight (SRB: 297.3±7.4, SLB: 311.6 ± 9.0). The beef group had a significantly higher mean carcass classification (6.2 ± 0.2) and a different age distribution with a higher proportion of heifers (38% cows, 12% young cows, and 50% heifers), but was comparable in body fat content (8.5 ± 0.4) and kilograms of carcass weight (310.9 ± 7.9). Cleavage rate, number of embryos developed beyond the 2-cell stage by 44 h post-fertilization, and the number of blastocysts developed by Days 7 and 8 were noted. All blastocysts were graded and stained with Hoechst 33 342 and the number of nuclei was determined. Cleavage rate was not different among the breeds (SRB: 71.9 ± 0.03%, SLB: 72.5 ± 0.02%, beef: 73.9 ± 0.03%). The percentage of embryos developed beyond 2-cells (from cleaved) did not differ between the beef and SRB (beef: 65.1 ± 6.1%; SRB: 70.4 ± 4.9%) but SLB was significantly greater than than the other breeds (75.4 ± 4.5%). The percentage of blastocysts developed by Day 8 was significantly higher in the beef (21.1 ± 2.7%) and SRB (23.3 ± 3.5%) breeds compared with the SLB (12.5 ± 2.4%). There was no significant difference in blastocyst grades among breeds (scale 1-4, where 1 = highest grade; SRB: 2.4 ± 0.1, SLB: 2.4 ± 0.2, beef: 2.1 ± 0.2), but the number of nuclei in Day 8 blastocysts was significantly lower in the SLB (SRB: 98.9 ± 7.7, SLB: 79.2 ± 8.7, beef: 101.4 ± 6.9). In conclusion, the breed of origin of the oocytes is an important factors affecting the development during in vitro embryo production in cattle. Funded by Formas.
32
Haferlach, Claudia, Vera Grossmann, Melanie Zenger, Tamara Alpermann, Alexander Kohlmann, Wolfgang Kern, Torsten Haferlach, and Susanne Schnittger. "The Prognostic Impact of High EVI1 expression In AML Is Due to Its Close Correlation to Rearrangements Involving EVI1 or MLL, which Are Cytogenetically Cryptic In a Subset of Patients: a Study on 332 Cases." Blood 116, no. 21 (November 19, 2010): 1676. http://dx.doi.org/10.1182/blood.v116.21.1676.1676.
Анотація:
Abstract Abstract 1676 Introduction: High EVI1 expression has been proposed as a negative prognostic factor in AML. An association between high EVI1 expression and distinct cytogenetic subgroups, such as 3q26-rearrangements, MLL-rearrangements and -7/7q- have been reported. Both 3q26- and MLL-rearrangements can be difficult to detect by chromosome banding analyses or may even be cytogenetically cryptic in a subset of patients due to limited resolution. Therefore, only studies using FISH for the detection of cryptic EVI1- or MLL-rearrangements can clarify their frequencies in AML with elevated EVI1 expression. Methods/Patients:: The study cohort was composed of 332 AML cases with a) normal karyotype (NK) (n=211), b) -7/7q- (n=77), and for comparison c) 3q26-rearrangements (n=38), and d) MLL-rearrangement (n=6). In all cases EVI1 expression was investigated using quantitative PCR calculating a % EVI1/ABL1 expression. In all cases FISH for EVI1 rearrangement was performed in addition to chromosome banding analysis. Cases with high EVI1 expression were also analyzed for MLL rearrangements by FISH. Results: In the total cohort, EVI1 expression varied between 0 and 1614 (median: 21.1). The highest EVI1 expression was measured in cases with cytogenetically identified 3q26-rearrangements (range: 6.1–566.4; median: 81.9) and in AML with MLL-rearrangements (range: 46.7–831; median: 239). The EVI1 expression was significantly lower in AML with NK (range: 0–1614; median: 0.5, p<0.001) and AML with -7/7q- (range: 0.03–199; mean: 34.5; median: 10.7, p<0.001). In the subgroup of cases with NK 4 MLL-rearrangements (1.9%) were detected by FISH and subsequently verified by fusion gene specific PCR. In addition, 4 cases with cryptic EVI1-rearrangements (1.9%) were identified by FISH analysis. Further genetic analysis revealed that these were due to t(3;8)(q26;q24) (n=2) and t(3;21)(q26;q11) (n=1). In one case, the EVI1-rearrangement could not be further analyzed due to lack of material. In the -7/7q- cohort 14/77 cases (18.2%) with cytogenetically cryptic EVI1 rearrangement including 3 novel recurrent abnormalities were detected: t(3;21)(q26;q11) (n=3), inv(3)(p24q26) (n=4) and t(3;8)(q26;q24) (n=2). In 5 cases FISH analysis revealed that the 7q- was not caused by an interstitial deletion but due to an unbalanced rearrangement between chromosomes 7 and 3: der(7)t(3;7)(q26;q21). In these 5 cases high-resolution SNP microarray were performed and revealed breakpoints in the CDK6 gene and centromeric of the EVI1 gene. Further mutation screening revealed that none of the cases with EVI1- or MLL-rearrangement harboured mutations in NPM1 or CEPBA. In 254 cases clinical follow-up data was available. Different cut-off levels of EVI1 expression were tested, and a cut-off at 30% EVI1/ABL1 expression was the lowest level that had a significant impact on outcome. Separating the cohort at this cut-off into high EVI1 (n=67) and low EVI1 expressors (n=187) showed a shorter EFS in patients with high EVI1-expression (p=0.001; relative risk (RR)=1.87, median EFS 6.2 vs 15.0 months (mo)), while no impact on OS was observed. When the same analyses were performed with respect to EVI1-rearrangements we observed both a significantly shorter EFS in cases with EVI1-rearrangement (n=39) vs all others (n=215) (p=0.001; RR=2.03, median EFS 4.6 vs 15.0 mo) and a significantly shorter OS (p=0.026; RR=1.73, median OS 10.1 vs 26.3 mo). Analyzing the impact of high EVI1 expression separately in the cohort without EVI1 rearrangement revealed no impact of EVI1 expression on EFS. Conclusions: The negative prognostic impact of high EVI1 expression is strongly associated with EVI1- or MLL-rearrangements and is absent in AML without EVI1- and MLL-rearrangement. Applying FISH in addition to chromosome banding analysis we identified cryptic rearrangements in 3.8% of AML with normal karyotype and in 18.2% of AML with -7/7q-, including 3 novel recurrent cytogenetically cryptic EVI1-rearrangements. This data supports the routine performance of FISH screening for EVI1- and MLL-rearrangements in patients with normal karyotype or 7q-/-7 and without NPM1 mutation and CEPBA mutation to assign patients to the correct biologic entity. The postulated independent prognostic impact of EVI1 expression should be tested further including this laboratory workflow as these parameters may have important impact on prognosis and future treatment strategies. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Grossmann:MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
33
Måwe, Leif, Lena Måwe Thorén, and Gunnvald Kvarstein. "Responses after spinal interventions in a clinical pain practice – a pragmatic observational study." Scandinavian Journal of Pain 20, no. 3 (July 28, 2020): 469–82. http://dx.doi.org/10.1515/sjpain-2019-0126.
Анотація:
AbstractIntroductionThere is limited evidence for effect of interventional treatment, and pragmatic studies are needed to assess these interventions within a clinical setting. The aim of this study was to describe patients referred to an interventional pain clinic and investigate responses after spinal intervention in general and for radiofrequency ablation (RFA) and transforaminal epidural corticosteroid administration (TECA), specifically.MethodsThis is a prospective, non-controlled study of patients with chronic spinal pain. The procedures were performed in accordance with the Spine Intervention Society recommendations. Outcome data after a median of 4.5 months are presented, and for those treated with RFA also after 6 and 12 months.ResultsAmong 815 patients, 190 patients underwent diagnostic blocks only and 625 interventional treatment, of these 94 RFA and 246 TECA. Of the whole sample 70% reported pain reduction, for 49% ≥ 50%, while 9% were pain free (p < 0.001). Highest pain intensity decreased from 7.1 to 5.4 [95% Confidence Interval of the Difference (95%-CI): 1.4–1.9] (p < 0.001), while Euroqual – visual analogue scale for general health (EQ-VAS) improved from 48 to 58 (95%-CI: 7.6–11.9) (p < 0.001), and Euroqual-5 Dimensions-5 Levels Index for health related quality of life (EQ-5D-5L Index) from 0.489 to 0.628 (95%-CI: 0.123–0.157) (p < 0.001). The proportions, not taking analgesics, increased from 16% to 30%, and proportion taking strong opioids decreased from 14% to 9% (p < 0.001). We found no significant change in proportion receiving physiotherapy/other treatment nor occupational status. No complications were reported. Among patients treated with RFA, 77% reported pain reduction, for 56% ≥ 50%, while 9% were pain free (p < 0.001). Highest pain intensity decreased from 6.9 to 4.6 (95%-CI: 1.6–3.0) (p < 0.001), while EQ-VAS improved from 47 to 57 (95%-CI: 4.8–13.6 (p < 0.001), and EQ-5D-5L Index from 0.489 to 0.643 (95%-CI: 0.117–0.191) (p < 0.001). The proportion not taking analgesics, increased from 7% to 23% and proportion taking strong opioids decreased from 16% to 10%. Among patients who responded at 6- and 12-month follow up, the proportions reporting pain reduction, EQ-VAS, and EQ-5D-5L Index remained significantly improved from baseline, and the change in proportions taking analgesic and opioids achieved statistical significance. We found no significant change in proportion receiving physiotherapy/other treatment nor occupational status. Among patients treated with TECA, 58% reported pain reduction, for 36% ≥ 50%, while 5% were pain free (p < 0.001). Highest pain intensity decreased from 7.2 to 6.2 (95%-CI 0.5–1.4) (p < 0.001), while EQ-VAS improved from 46 to 52 (95%-CI: 2.0–3.6) (p < 0.001), and EQ-5D-5L Index from 0.456 to 0.571 (95%-CI: 0.077–0.138) (p < 0.001). The proportions, not taking analgesics, increased from 17% to 27% and proportion taking strong opioids decreased from 15% to 10%, but the changes did not reach statistical significance. We found no significant changes in the proportion who recieved physiotherapy/other treatment nor occupational status.ConclusionThe study demonstrates substantial short-term responses after spinal intervention and long-lasting improvement for a subsample of the RFA treated patients. We observed larger proportions reporting pain reduction among those treated with cervical RFA.ImplementationQuality assessment should be implemented in interventional pain clinics to improve treatment quality.
34
Łosińska, K., M. Wilk, A. H. Pripp, M. Korkosz, and G. Haugeberg. "AB0219 EXPLORING LONG-TERM DRUG EFFECTIVENESS AND DRUG SURVIVAL FOR RITUXIMAB REFERENCE DRUG IN TREATMENT OF RHEUMATOID ARTHRITIS PATIENTS IN ORDINARY OUTPATIENT CLINIC." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1135.3–1136. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1661.
Анотація:
Background:In randomized controlled trials (RCTs) rituximab (RTX) has been shown to effectively suppress inflammation and reduce structural joint damage in rheumatoid arthritis (RA) patients [1]. There is a lack of RA data on RTX effectiveness and drug survival when used in real life practice.Objectives:To explore long-term drug effectiveness and drug survival for RTX used to treat RA patients in ordinary clinical practice.Methods:The study population included RA patients treated between 2006 and 2020 with RTX at an outpatient clinic in Norway. Patients were monitored using recommended measures for disease activity and patient reported outcomes (PROs). Drug effectiveness was assessed with random intercept linear mixed models. Drug survival was described using Kaplan-Meier survival analysis. Baseline predictors of drug survival were assessed with multivariable Cox proportional hazard models.Results:In database a total of 246 RA patients (females 74.8%) were identified to have been treated with RTX. At baseline mean (SD) age was 59.1 (13.5) years, disease duration 13.0 (10.2) years, RF positive 88.8%, ACPA positive 92.1%. Majority of patients had first cycle RTX dosage of 2000 mg (82.9%). At baseline patients currently using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were 51.5% (methotrexate 39.4%), prednisolone 73.6% and a total of 17.1% were biologic DMARDs (bDMARDs) naïve. In table 1 mean (SE) values for disease activity and PROs are shown for baseline and subsequent years after baseline for 5 years follow up.Table 1.Changes in disease activity and PROs at baseline and subsequent 1-year periodsBaselineN=2461 yearN=2462 yearN=2043 yearN=1634 yearN=1305 yearN=111CRP (mg/L)23.1 (2.1)21.3 (1.6)11.7 (0.9)8.6 (1.4)6.2 (0.7)6.7 (0.9)ESR (mm/hr)32.1 (1.4)31.1 (1.3)22.3 (1.1)17.6 (1.2)14.3 (1.0)13.6 (1.2)SJC28 (0-28)6.3 (0.4)5.4 (0.3)3.2 (0.3)2.2 (0.2)1.6 (0.2)1.5 (0.2)TJC28 (0-28)7.1 (0.4)6.6 (0.3)3.6 (0.3)2.6 (0.3)2.2 (0.3)1.8 (0.3)DAS284.9 (0.1)4.7 (0.1)3.6 (0.1)3.1 (0.1)2.8 (0.1)2.7 (0.1)CDAI22.9 (0.9)20.7 (0.7)12.3 (0.7)9.4 (0.7)8.5 (0.6)7.7 (0.7)PGA (0-100mm)57.2 (1.7)53.7 (1.4)38.1 (1.6)33.7 (1.9)35.0 (2.1)32.8 (2.2)MHAQ (0-3)1.0 (0.0)0.9 (0.0)0.7 (0.0)0.6 (0.0)0.5 (0.0)0.5 (0.0)During follow up all disease activity and PRO measures improved significantly (p <0.001). Least improvement was seen in first year and a more substantial improvement progressed since second year. Percentage of patients with no, moderate and good treatment response defined according to EULAR response criteria [2] is shown in figure 1.Figure 1.No, moderate and good response to RTX treatmentNo significant difference during the 5-year follow-up was found regarding previous use of bDMARD or not and for concomitant use of csDMARDs or not for variables listed in the table 1.Drug survival for the RTX was 83% (95CI 77-87%) after 1 year, 66% (95CI 60-72%) after 2 years, 53% (95CI 46-59%) after 3 years, 46% (95CI 39-52%) after 4 years and 34% (95CI 28-40%) after 5 years of follow up.No significant difference in drug survival was found between bDMARD naïve and previous users of bDMARDs or between concomitant and non-concomitant users of csDMARDs. RF positive patients had a better drug survival.In prediction analysis RF positive status, high baseline DAS28, low baseline CRP, previous bDMARDs use, short disease duration and low MHAQ were found to be independently associated with better drug survival.Conclusion:Our real life data shows that RTX treated RA patients had a satisfactory treatment response and drug survival declines rather linearly over time. However, a significant treatment response was achieved primary in the second year indicating that at least 2 twin infusions should be given before identifying treatment failure.References:[1]Mok CC. Rituximab for the treatment of rheumatoid arthritis: An update. Drug Des Devel Ther 2013;8:87-100.[2]Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009;35:745-viii.Acknowledgements:Nurses and doctors from Division of Rheumatology at Sørlandet Hospital in Kristiansand, Norway contributed to data collection.Disclosure of Interests:None declared
35
Delaney, Colleen, Filippo Milano, Ian Nicoud, Shelly Heimfeld, Chatchada Karanes, Jonathan A. Gutman, John E. Wagner, Frederick R. Appelbaum, and Irwin D. Bernstein. "Dose Dependent Enhancement Of Neutrophil Recovery By Infusion Of Notch Ligand Ex Vivo Expanded Cord Blood Progenitors: Results Of a Multi-Center Phase I Trial." Blood 122, no. 21 (November 15, 2013): 297. http://dx.doi.org/10.1182/blood.v122.21.297.297.
Анотація:
Abstract Introduction There is a strong clinical need to overcome the increased early non relapse mortality (NRM) associated with delayed neutrophil recovery following cord blood transplant (CBT). Therefore we established a methodology using Notch ligand (Delta1) as a strategy for increasing the absolute number of marrow repopulating CB hematopoietic stem/progenitor cells (HSPC). We previously reported preliminary results of the first 10 patients in 2010 demonstrating the ability of Notch-expanded CB HSPC to provide rapid myeloid recovery post-CBT.1 Herein we present the updated results on 23 patients accrued to this trial aimed at assessment of efficacy as well as the feasibility of overnight shipment of the expanded cell product to three outside institutions. Methods Between July 2006 and March 2013, 23 patients with hematologic malignancies were enrolled in this prospective multi-center Phase I trial coordinated by the Fred Hutchinson Cancer Research Center in which one CB unit was ex vivo expanded prior to infusion. Conditioning consisted of Fludarabine (75mg/m2), Cyclophosphamide (120mg/kg) and TBI (13.2 Gy) over 8 days. On day 0, the unmanipulated CB unit was infused first followed 4 hours later by infusion of the freshly harvested expanded CB cells. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine and MMF beginning on day -3. All CB grafts were 4-6/6 HLA-matched (A/B antigen level, DRB1 allele level) to the recipient. Engraftment, NRM, relapse and GVHD were calculated using cumulative incidence rates to accommodate competing risks. Overall survival was analyzed using Kaplan-Meier estimates. Results Patient diagnosis was AML (n=16), ALL (n=5) and biphenotypic leukemia (n=2). Nine patients (39%) were ≥CR2 and 5 were MRD+ at the time of transplant. Median age was 28 years (range, 4-43) and weight 70 kg (range, 16-91) with a median follow-up of 614 days (range, 271-2443). 22 patients received the expanded graft with one product not meeting release criteria. The cell doses infused were significantly higher in the expanded CB graft: 2.7 (1.5-6.3) vs 6.9 (0.4-27.6) x107 TNC/kg, p<0.0008; 0.15 (0.02-0.57) vs 7.7 (0.62-49.5) x106 CD34/kg, p<0.0001. HLA-matching and ABO incompatibility of the expanded and unmanipulated products were similar. The incidence of neutrophil recovery was 95% (95% CI, 71-100) at a median of 13 days (range, 6-41 days) among the 22 patients receiving expanded CB cells which is significantly faster than that observed in 40 recipients of two unmanipulated units otherwise treated identically at a median time of 25 days (range, 14 to 45; p<0.0001). The incidence of platelet recovery (>20 x 10^9/L) was 77% (CI 95%: 53- 89) by day 100 at a median of 38 days (range, 19 – 134). There was one case of primary graft failure. Importantly, rate of neutrophil recovery correlated with CD34+ cell dose/kg with 8 out of 11 patients receiving greater than 8x106 CD34+cells/kg achieved an ANC ≥ 500/µl within 10 days. 21 patients were evaluable for in vivo persistence of the expanded cells. Ten (48%) demonstrated in vivo persistence beyond one month post infusion. The expanded cell graft was persistent at day 180 in 7 patients, and in those that survived to one year, dominance of the expanded cell graft persisted in one patient. The incidences of grade II-IV and III-IV acute GVHD was 77% (95% CI, 53-89) and 18% (95% CI, 5-36%), respectively; mild chronic GVHD was observed in 4 patients and severe chronic GVHD in one. Probability of OS was 62% (95% CI, 37-79%) at 4 years. Notably, the cumulative incidence of NRM at day 100 was 8% (95% CI, 14-24%) and at 4 years was 32% (95% CI, 8-40%). Nine patients died at a median time of 216 days (range, 31-1578 days) with respiratory failure/infection the most common cause (n=6). There were two relapses at day 156 and 365 post-transplant, with one death due to relapse. Secondary malignancy and primary graft failure were the other 2 causes of death. Conclusions Infusion of Notch-expanded CB progenitors is safe and effective, significantly reducing the time to neutrophil recovery and risks of NRM during the first 100 days. An advantage for infusion of higher numbers of CD34+ cells/kg further demonstrates the need to develop methods that reproducibly provide even greater expansion of repopulating cells than currently achieved to improve efficacy and potentially cost effectiveness. 1. Delaney C, et al, Nat Med. 2010 Feb;16(2):232-6. Disclosures: Delaney: Novartis: DSMB, DSMB Other; Biolife: Membership on an entity’s Board of Directors or advisory committees; medac: Research Funding. Wagner:Novartis: Research Funding; cord use: Membership on an entity’s Board of Directors or advisory committees.
36
Rahardjo, Maria Melita. "How to use Loose-Parts in STEAM? Early Childhood Educators Focus Group discussion in Indonesia." JPUD - Jurnal Pendidikan Usia Dini 13, no. 2 (December 1, 2019): 310–26. http://dx.doi.org/10.21009/jpud.132.08.
Анотація:
In recent years, STEAM (Science, Technology, Engineering, Art, and Mathematics) has received wide attention. STEAM complements early childhood learning needs in honing 2nd century skills. This study aims to introduce a loose section in early childhood learning to pre-service teachers and then to explore their perceptions of how to use loose parts in supporting STEAM. The study design uses qualitative phenomenological methods. FGDs (Focus Group Discussions) are used as data collection instruments. The findings point to two main themes that emerged from the discussion: a loose section that supports freedom of creation and problem solving. Freedom clearly supports science, mathematics and arts education while problem solving significantly supports engineering and technology education.
Keywords: Early Childhood Educators, Loose-part, STEAM
References:
Allen, A. (2016). Don’t Fear STEM: You Already Teach It! Exchange, (231), 56–59.
Ansberry, B. K., & Morgan, E. (2019). Seven Myths of STEM. 56(6), 64–67.
Bagiati, A., & Evangelou, D. (2015). Engineering curriculum in the preschool classroom: the teacher’s experience. European Early Childhood Education Research Journal, 23(1), 112–128. https://doi.org/10.1080/1350293X.2014.991099
Becker, K., & Park, K. (2011). Effects of integrative approaches among science , technology , engineering , and mathematics ( STEM ) subjects on students ’ learning : A preliminary meta-analysis. 12(5), 23–38.
Berk, L. E. (2009). Child Development (8th ed.). Boston: Pearson Education.
Can, B., Yildiz-Demirtas, V., & Altun, E. (2017). The Effect of Project-based Science Education Programme on Scientific Process Skills and Conception of Kindergargen Students. 16(3), 395–413.
Casey, T., Robertson, J., Abel, J., Cairns, M., Caldwell, L., Campbell, K., … Robertson, T. (2016). Loose Parts Play. Edinburgh.
Cheung, R. H. P. (2017). Teacher-directed versus child-centred : the challenge of promoting creativity in Chinese preschool classrooms. Pedagogy, Culture & Society, 1366(January), 1–14. https://doi.org/10.1080/14681366.2016.1217253
Clements, D. H., & Sarama, J. (2016). Math, Science, and Technology in the Early Grades. The Future of Children, 26(2), 75–94.
Cloward Drown, K. (2014). Dramatic lay affordances of natural and manufactured outdoor settings for preschoolaged children.
Dejarnette, N. K. (2018). Early Childhood Steam: Reflections From a Year of Steam Initiatives Implemented in a High-Needs Primary School. Education, 139(2), 96–112.
DiGironimo, N. (2011). What is technology? Investigating student conceptions about the nature of technology. International Journal of Science Education, 33(10), 1337–1352. https://doi.org/10.1080/09500693.2010.495400
Dugger, W. E., & Naik, N. (2001). Clarifying Misconceptions between Technology Education and Educational Technology. The Technology Teacher, 61(1), 31–35.
Eeuwijk, P. Van, & Zuzana, A. (2017). How to Conduct a Focus Group Discussion ( FGD ) Methodological Manual.
Flannigan, C., & Dietze, B. (2018). Children, Outdoor Play, and Loose Parts. Journal of Childhood Studies, 42(4), 53–60. https://doi.org/10.18357/jcs.v42i4.18103
Fleer, M. (1998). The Preparation of Australian Teachers in Technology Education : Developing The Preparation of Australian Teachers in Technology Education : Developing Professionals Not Technicians. Asia-Pacific Journal of Teacher Education & Development, 1(2), 25–31.
Freitas, H., Oliveira, M., Jenkins, M., & Popjoy, O. (1998). The focus group, a qualitative research method: Reviewing the theory, and providing guidelines to its planning. In ISRC, Merrick School of Business, University of Baltimore (MD, EUA)(Vol. 1).
Gomes, J., & Fleer, M. (2019). The Development of a Scientific Motive : How Preschool Science and Home Play Reciprocally Contribute to Science Learning. Research in Science Education, 49(2), 613–634. https://doi.org/10.1007/s11165-017-9631-5
Goris, T., & Dyrenfurth, M. (n.d.). Students ’ Misconceptions in Science , Technology , and Engineering .
Gull, C., Bogunovich, J., Goldstein, S. L., & Rosengarten, T. (2019). Definitions of Loose Parts in Early Childhood Outdoor Classrooms: A Scoping Review. The International Journal of Early Childhood Environmental Education, 6(3), 37.
Hui, A. N. N., He, M. W. J., & Ye, S. S. (2015). Arts education and creativity enhancement in young children in Hong Kong. Educational Psychology, 35(3), 315–327. https://doi.org/10.1080/01443410.2013.875518
Jarvis, T., & Rennie, L. J. (1996). Perceptions about Technology Held by Primary Teachers in England. Research in Science & Technological Education, 14(1), 43–54. https://doi.org/10.1080/0263514960140104
Jeffers, O. (2004). How to Catch a Star. New York: Philomel Books.
Kiewra, C., & Veselack, E. (2016). Playing with nature: Supporting preschoolers’ creativity in natural outdoor classrooms. International Journal of Early Childhood Environmental Education, 4(1), 70–95.
Kuh, L., Ponte, I., & Chau, C. (2013). The impact of a natural playscape installation on young children’s play behaviors. Children, Youth and Environments, 23(2), 49–77.
Lachapelle, C. P., Cunningham, C. M., & Oh, Y. (2019). What is technology? Development and evaluation of a simple instrument for measuring children’s conceptions of technology. International Journal of Science Education, 41(2), 188–209. https://doi.org/10.1080/09500693.2018.1545101
Liamputtong. (2010). Focus Group Methodology : Introduction and History. In Focus Group MethodoloGy (pp. 1–14).
Liao, C. (2016). From Interdisciplinary to Transdisciplinary: An Arts-Integrated Approach to STEAM Education. 69(6), 44–49. https://doi.org/10.1080/00043125.2016.1224873
Lindeman, K. W., & Anderson, E. M. (2015). Using Blocks to Develop 21st Century Skills. Young Children, 70(1), 36–43.
Maxwell, L., Mitchell, M., and Evans, G. (2008). Effects of play equipment and loose parts on preschool children’s outdoor play behavior: An observational study and design intervention. Children, Youth and Environments, 18(2), 36–63.
McClure, E., Guernsey, L., Clements, D., Bales, S., Nichols, J., Kendall-Taylor, N., & Levine, M. (2017). How to Integrate STEM Into Early Childhood Education. Science and Children, 055(02), 8–11. https://doi.org/10.2505/4/sc17_055_02_8
McClure, M., Tarr, P., Thompson, C. M., & Eckhoff, A. (2017). Defining quality in visual art education for young children: Building on the position statement of the early childhood art educators. Arts Education Policy Review, 118(3), 154–163. https://doi.org/10.1080/10632913.2016.1245167
Mishra, L. (2016). Focus Group Discussion in Qualitative Research. TechnoLearn: An International Journal of Educational Technology, 6(1), 1. https://doi.org/10.5958/2249-5223.2016.00001.2
Monhardt, L., & Monhardt, R. (2006). Creating a context for the learning of science process skills through picture books. Early Childhood Education Journal, 34(1), 67–71. https://doi.org/10.1007/s10643-006-0108-9
Monsalvatge, L., Long, K., & DiBello, L. (2013). Turning our world of learning inside out! Dimensions of Early Childhood, 41(3), 23–30.
Moomaw, S. (2012). STEM begins in the early years. School Science & Mathematics, 112(2), 57–58.
Moomaw, S. (2016). Move Back the Clock, Educators: STEM Begins at Birth. School Science & Mathematics, 116(5), 237–238.
Moomaw, S., & Davis, J. A. (2010). STEM Comes to Preschool. Young Cihildren, 12–18(September), 12–18.
Munawar, M., Roshayanti, F., & Sugiyanti. (2019). Implementation of STEAM (Science, Technology, Engineering, Art, Mathematics)-Based Early Childhood Education Learning in Semarang City. Jurnal CERIA, 2(5), 276–285.
National Research Council. (1996). National Science Education Standards. Washington, DC: National Academy of Sciences.
Nicholson, S. (1972). The Theory of Loose Parts: An important principle for design methodology. Studies in Design Education Craft & Technology, 4(2), 5–12.
O.Nyumba, T., Wilson, K., Derrick, C. J., & Mukherjee, N. (2018). The use of focus group discussion methodology: Insights from two decades of application in conservation. Methods in Ecology and Evolution, 9(1), 20–32. https://doi.org/10.1111/2041-210X.12860
Padilla-Diaz, M. (2015). Phenomenology in Educational Qualitative Research : Philosophy as Science or Philosophical Science ? International Journal of Educational Excellence, 1(2), 101–110.
Padilla, M. J. (1990). The Science Process Skills. Research Matters - to the Science Teacher, 1(March), 1–3.
Park, D. Y., Park, M. H., & Bates, A. B. (2018). Exploring Young Children’s Understanding About the Concept of Volume Through Engineering Design in a STEM Activity: A Case Study. International Journal of Science and Mathematics Education, 16(2), 275–294. https://doi.org/10.1007/s10763-016-9776-0
Rahardjo, M. M. (2019). Implementasi Pendekatan Saintifik Sebagai Pembentuk Keterampilan Proses Sains Anak Usia Dini. Scholaria: Jurnal Pendidikan Dan Kebudayaan, 9(2), 148–159. https://doi.org/10.24246/j.js.2019.v9.i2.p148-159
Robison, T. (2016). Male Elementary General Music Teachers : A Phenomenological Study. Journal of Music Teacher Education, 26(2), 77–89. https://doi.org/10.1177/1057083715622019
Rocha Fernandes, G. W., Rodrigues, A. M., & Ferreira, C. A. (2018). Conceptions of the Nature of Science and Technology: a Study with Children and Youths in a Non-Formal Science and Technology Education Setting. Research in Science Education, 48(5), 1071–1106. https://doi.org/10.1007/s11165-016-9599-6
Sawyer, R. K. (2006). Educating for innovation. 1(2006), 41–48. https://doi.org/10.1016/j.tsc.2005.08.001
Sharapan, H. (2012). ERIC - From STEM to STEAM: How Early Childhood Educators Can Apply Fred Rogers’ Approach, Young Children, 2012-Jan. Young Children, 67(1), 36–40.
Siantayani, Y. (2018). STEAM: Science-Technology-Engineering-Art-Mathematics. Semarang: SINAU Teachers Development Center.
Sikder, S., & Fleer, M. (2015). Small Science : Infants and Toddlers Experiencing Science in Everyday Family Life. Research in Science Education, 45(3), 445–464. https://doi.org/10.1007/s11165-014-9431-0
Smith-gilman, S. (2018). The Arts, Loose Parts and Conversations. Journal of the Canadian Association for Curriculum Studies, 16(1), 90–103.
Sohn, B. K., Thomas, S. P., Greenberg, K. H., & Pollio, H. R. (2017). Hearing the Voices of Students and Teachers : A Phenomenological Approach to Educational Research. Qualitative Research in Education, 6(2), 121–148. https://doi.org/10.17583/qre.2017.2374
Strong-wilson, T., & Ellis, J. (2002). Children and Place : Reggio Emilia’s Environment as Third Teacher. Theory into Practice, 46(1), 40–47.
Sutton, M. J. (2011). In the hand and mind: The intersection of loose parts and imagination in evocative settings for young children. Children, Youth and Environments, 21(2), 408–424.
Tippett, C. D., & Milford, T. M. (2017). Findings from a Pre-kindergarten Classroom: Making the Case for STEM in Early Childhood Education. International Journal of Science and Mathematics Education, 15, 67–86. https://doi.org/10.1007/s10763-017-9812-8
Tippett, C., & Milford, T. (2017). STEM Resources and Materials for Engaging Learning Experiences. International Journal of Science & Mathematics Education, 15(March), 67–86. https://doi.org/10.1007/s10763-017-9812-8
Veselack, E., Miller, D., & Cain-Chang, L. (2015). Raindrops on noses and toes in the dirt: infants and toddlers in the outdoor classroom. Dimensions Educational Research Foundation.
Yuksel-Arslan, P., Yildirim, S., & Robin, B. R. (2016). A phenomenological study : teachers ’ experiences of using digital storytelling in early childhood education. Educational Studies, 42(5), 427–445. https://doi.org/10.1080/03055698.2016.1195717
37
Dittrich, Tobias, Ute Hegenbart, Tilmann Bochtler, Christoph Kimmich, Anna Jauch, Arnt Kristen, Hartmut Goldschmidt, Anthony D. Ho, and Stefan Schönland. "Clinical and Cytogenetic Characterization of Light Chain Amyloidosis Patients with a Low Amyloidogenic Free Light Chain Count at First Diagnosis." Blood 126, no. 23 (December 3, 2015): 1790. http://dx.doi.org/10.1182/blood.v126.23.1790.1790.
Анотація:
Abstract Background: Systemic light chain amyloidosis (AL) is a rare and life-threatening protein-deposition disorder. The diagnosis and especially quantification of the underlying, usually small clonal B cell disorder in patients with very low levels of free kappa or lambda light chains in serum (FLC) can be challenging. DFLC (difference of involved minus uninvolved FLC) response to therapy is hardly assessable for initial values below 50 mg/l. Consequently, these patients are frequently excluded from prospective and retrospective studies. Objective: Characterization of AL amyloidosis patients with dFLC<50. Methods: We have retrospectively analysedthe clinical features and long-termoutcome of 611 newly diagnosed AL patients with available dFLC and cytogenetic evaluation by iFISH at their first visit to our center between 2003-2014. Results: Clinical characteristics and detailed results are depicted in table 1. Patients with dFLC<50 significantly showed lower bone marrow plasma cell counts (6% vs. 10%, p<0.001), M-spike (7 g/l vs. 9 g/l, p<0.001) and concentrations of the monoclonal heavy chain (7 g/l vs. 10 g/l, p=0.003), while the mere presence of a monoclonal heavy chain in immunofixation (IF) was more frequent in these patients (55% vs. 38%, p=0.003). All analysed chromosomal aberrations were not associated with dFLC<50 (all p-values >0.05). Patients with cardiac (40% vs. 82%, p<0.001) and soft tissue (26% vs. 42%, p=0.005) involvement, higher Mayo Score and lower Karnofsky Index (KI) were much less frequently found in the group with initial dFLC<50, while kidney involvement was more common (85% vs. 58%, p<0.001). This, however, was not associated with a significantly worse renal function at diagnosis. Median overall survival (OS) was significantly better in patients with dFLC<50 regardless of treatment type (Figure 1): Bortezomib (77 vs. 16 months, p=0.006), Melphalan-Dexamethason (Mdex, 96 vs. 19 months, p=0.001) and high-dose Melphalan (HDM, not reached vs. 99 months, p=0.005). Conclusion: AL patients with an initial dFLC<50 mg/l represent a distinct clinical entity characterized by infiltration of the marrow with a small plasma cell clone and frequent presence of a monoclonal intact heavy chain, but with a low clonal heavy chain load. Importantly, this group of patients is not associated with any particular chromosomal aberrations as revealed by iFISH. This entity is further associated with a distinct pattern of organ involvement, i.e. a low Mayo Score, more than 80% of patients with renal amyloidosis, and very favourable OS irrespective of primary treatment regimens. Results of prospective clinical trials might be adversely influenced by the exclusion of these patients. Table 1. Parameter All patientsn=611 dFLC < 50 mg/ln=85 dFLC ≥ 50 mg/ln=526 p values Age in years, median [range] 66 [38-90] 65 [47-90] 66 [38-90] n.s. Sex female, no. of pts (%) 235 (39) 39 (46) 196 (37) n.s. Plasma cell related factors dFLC in mg/l, median [range] 228 [1-12.078] 29 [1-49] 279 [50-12.078] - Monoclonal heavy chain in IF, no. of pts (%) 248 (41) 47 (55) 201 (38) 0.003 M-spike in g/l, median [range]Evaluable pts (%) 9 [1-41]159 (26) 7 [1-22]31 (36) 9 [1-41]128 (24) <0.001 Involved heavy chain in g/l,median [range]Evaluable pts (%) 9.6 [0.5-197]243 (40) 6.8 [1.2-26]45 (53) 10.2 [0.5-197]198 (38) 0.003 Involved light chain λ, no. of pts (%) 490 (80) 73 (86) 417 (79) n.s. BM plasma cell count in %,median [range] 10 [1-90] 6 [1-40] 10 [1-90] <0.001 iFISH results, no. of pts (%) t(11;14) 350 (58) 42 (51) 308 (59) n.s. del 13q14 201 (33) 27 (33) 174 (33) n.s. gain 1q21 166 (27) 22 (26) 144 (27) n.s. Hyperdiploidy (Wuilleme Score) 98 (16) 12 (14) 86 (16) n.s. High-risk (del 17p13, t(4;14), t(14;16)) 47 (8) 7 (8) 40 (8) n.s. Organ involvement Number of Organs,median [range] 2 [1-6] 2 [1-6] 3 [1-6] 0.001 Heart, no. of pts (%) 463 (76) 34 (40) 429 (82) <0.001 Cardiac Mayo Score 2004: I, no. of pts (%)II, no. of pts (%)III, no. of pts (%) 101 (18)214 (38)255 (45) 35 (46)30 (40)11 (15) 66 (13)184 (37)244 (49) <0.001 Kidney, no. of pts (%) 376 (62) 72 (85) 304 (58) <0.001 MDRD, median [range] 64 [2-264] 68 [8-149] 63 [2-264] n.s. Soft Tissue, no. of pts (%) 243 (40) 22 (26) 221 (42) 0.005 KI %, median [range] 80 [40-100] 90 [50-100] 80 [40-100] 0.001 Treatment groups, no. of pts / median follow-up in months, median OS Bortezomib 214 / 2724 23 / 1977 191 / 2816 0.006 Mdex 156 / 7427 21 / 7596 135 / 7019 0.001 HDM 115 / 75129 24 / 75not reached 91 / 6999 0.005 Figure 1. Figure 1. Disclosures Hegenbart: Janssen: Honoraria. Bochtler:TEVA: Other: travel support. Goldschmidt:Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Honoraria, Research Funding, Speakers Bureau; Millenium: Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Schönland:Janssen, Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
38
Burbury, Kate, Peter C. Gambell, Amanda Choo, Jennifer Curnow, Kevin Lynch, Simon J. Harrison, Hang Quach, David Ritchie, Miles Prince, and David Alan A. Westerman. "Novel Thrombogenic Biomarkers In Patients with Relapsed/Refractory Multiple Myeloma (MM) Treated with Lenalidomide (LEN) and Dexamethasone (Dex) Therapy." Blood 116, no. 21 (November 19, 2010): 3187. http://dx.doi.org/10.1182/blood.v116.21.3187.3187.
Анотація:
Abstract Abstract 3187 Thromboembolism (TE) is an important complication of cancer with substantial clinical implications. MM, treated with thalidomide (thal) and LEN, has TE rates up to 25%, particularly when used in combination with chemotherapy and corticosteroids. Given disease heterogeneity, bleeding and TE risks are different for all patients and individuals over time. With the emergence of novel antithrombotic agents, further understanding of the pathophysiology of both MM- and therapy-related hemostatic dysfunction and the identification of important biomarkers, may promote a risk-stratification process and allow a targeted therapeutic strategy. We prospectively and sequentially assessed novel thrombogenic biomarkers, with a plan to correlate with functional assays (thrombin generation and microparticles) in R-MM, before and after exposure to LEN/dex as part of a 150-patient phase-II clinical trial. Hemostatic assessments were performed at enrolment, 1-, 4-, 12-months and/or end of study. 27 patients at our institution, 15 males, median age 69 years (range 58–80) were included in the analysis: 16 had IgG monoclonal protein (13 kappa [k]), 9 IgA (6 k), 2 were k light chain only. The karyotype was diploid in 18, complex in 4 and 3 patients had t(4;14), t(11;14) or t(8;14) respectively. Median number of prior lines of therapy was 3 (range 1–7); 18 had prior thal and 15 had received a melphalan-based autologous stem cell transplant. Median (range) for Hb was 111g/L (80-137) and creatinine clearance 66.6mL/min (23-182). 6/27 had a prior TE: 1 arterial, 5 venous. All patients commenced antithrombotic therapy at enrolment: 20 received aspirin (100mg/day), 4 prophylactic and 2 therapeutic dose enoxaparin, 1 treatment dose warfarin. At enrolment (pre-LEN/dex) and after 4 weeks of therapy, the median (range) for the individual assays are outlined in table 1. Pre-LEN/dex: FVIIIc, vWFAg, Fib Mon, TAT, PF1+2 and TM were markedly elevated in the majority of patients. After 4 weeks of therapy, many biomarkers remained elevated, however, Fib Mon and PMN-E near normalised in all patients; FVIIIC and vWFAg was elevated in less patients; while Fib, PF1+2 and TAT increased. This early promising data demonstrate inflammatory, endothelial and hemostatic dysregulation in R-MM with an altered biomarker profile after exposure to LEN/dex. Further results of sequential analyses will be presented at the meeting. Study (cycle, day) C1D1 (pre–LEN/dex) n* C2D1 (4–weeks LEN/dex) n* Biomarker (units, NR) Median Range >ULN, <LLN Median Range >ULN <LLN APTT (s, 24–34) 34 24–48 13 0 33 26–52 8 0 PT (s, 11.8–14.6) 13.5 12–25.6 10 0 13.2 11.2–45.2 2 3 Fib (g/L, 2.0–4.0) 4 2.4–6.8 12 0 5.5 0.7–8.4 21 2 D-dimer (mg/L, 0.0–0.5) 0.5 0.1-1.5 9 NA 0.6 0.1–6.4 15 NA Plt (×109/L, 150–450) 214 43–372 0 7 225 30–385 0 6 FVIIIc (%, 50–150) 298 96–600 22 0 236.5 159–600 10 0 vWFAg (%, 50–160) 206 98–325 18 0 298 148–364 12 0 APC-R ratio (2–3.5) 2.3 1.7–3.4 0 3 3.2 1.7–3.6 1 1 AT (%, 80–120) 98 69–135 3 3 108 77–126 4 1 Fib Mon (μg/ml, 0.1– 6) 4.3 2.0–61.2 8 0 3.1 0–95 2 1 TAT (μg/L, <2.0–4.2) 1.1 0.4–37.6 9 14 8.1 2.7–54.7 19 0 PF1+2 (pmol/L, 69–229) 192.3 0.7–705.5 11 2 197.3 35.8–1266.5 8 5 anti-CG (U/ml, <15) 0.2 0-5.2 0 NA 0.1 0–0.6 0 NA TM (pg/mL, 2353–4541) 4739.1 2628–11656.3 15 0 4050.3 244–10613.2 8 2 PMN-E (ng/mL, 0–90) 44 22–276 6 NA 34.8 14–92 1 NA NR: Normal range; APTT: Activated partial thromboplastin time; PT: Prothrombin time; Fib: Fibrinogen; Plt: Platelet count; FVIIIc: Factor VIII-coagulant; vWFAg: von Willebrand factor Antigen; APC-R: Activated protein C resistance ratio; AT: Antithrombin; Fib Mon: Fibrin Monomers; TAT: Thrombin-antithrombin complex; PF1+2: Prothrombin fragments1+2; CG: Cathepsin G; TM: Thrombomodulin; PMN-E: PMN Elastase; NA: values <LLN or >ULN not clinically applicable. * Number of patients (n) within the cohort (n=27), in whom measured level was >upper limit of normal (>ULN) or <lower limit of normal (<LLN). Disclosures: Curnow: Celgene: Research Funding; Novartis: Consultancy. Lynch:Celgene Pty Ltd: Employment, Equity Ownership. Harrison:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Prince:Celegene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Westerman:Celgene: Research Funding.
39
Dumont, Larry J., James P. AuBuchon, Louise Herschel, Jill Roger, Thayer White, and Adonis Stassinopoulos. "Random Healthy Donor Sera Show Varying Effectiveness in Hemolyzing ABO Incompatible Red Blood Cells." Blood 108, no. 11 (November 16, 2006): 958. http://dx.doi.org/10.1182/blood.v108.11.958.958.
Анотація:
Abstract Mixing of allogeneic serum with RBC that are ABO-incompatible is well known to cause lysis of the RBC. However, the severity and extent of such hemolysis may not be the same for every mismatched pairing and is not documented in the literature. We were interested in quantitating the lytic potential of a large panel of normal sera when exposed to ABO-incompatible RBC. We collected 80mL of whole blood in red-top tubes from 110 random healthy subjects (84 female 26 male) with blood Groups A (n=6), AB (n=5), B (n=10) and O (n=89). Sera were prepared by clotting at room temp, frozen in aliquots, stored at −80°C. CPD whole blood (N=14) from healthy subjects were obtained commercially, shipped and stored per standard methods (A1: 8, A2: 2, O: 4). Forward ABO typing on all serum subjects and whole blood was with Immucor-Gamma murine monoclonal antibody reagents. Within 48 h of donation, packed RBC were prepared by centrifugation of an aliquot at 900xg for 5 min. RBC were resuspended in AS-3 to a final hematocrit of 10%. Total Hb was measured on a BayerAdvia120 analyzer, and hematocrit was determined by capillary tube centrifugation. Aliquots of 125μL of this RBC suspension were incubated with 250μL aliquots of the serum panel for 30 min at 37°C followed by double centrifugation at 900xg for 5 min. Supernatant (sup) was assayed for Hb by the cyanmethemoglobin method reading on a spectrophotometer at 540nm with a turbidity correction for 680nm absorbance. Results were corrected for test serum and RBC plasma absorbances. Percent hemolysis was calculated as 100xHb(sup, mg/dL)x(1-hct)/Hb(total, mg/dL). A repeated measures analysis of variance mixed-effects model was used to test the effect of serum-donor sex, serum-donor ABO group and RBC ABO group on hemolysis. Sup Hb was categorized into visually detectable hemolysis (>56 mg/dL; Elliot et al, Transfusion2003;43:297) or not. A total of 1462 plasma-RBC incubations were carried out, with each of the 110 test sera tested versus the test RBC. As expected, no significant hemolysis was detected for ABO-compatible combinations (p>0.8). Complete hemolysis was not observed in any combination. Of the 89 O-sera, median hemolysis with A1-RBC was 3.9% (max 33.4%), but only a median of 0.9% (max of 17.5%) with A2-RBC. There was no significant effect of serum-donor gender on hemolysis (p=0.8). Group O-sera caused higher average hemolysis than B sera for both A1 and A2-RBC. A1-RBC had a larger hemolytic response to both sera types. Notably, not all sera of the same ABO-group caused equivalent hemolysis. We observed a larger variation in hemolysis between serum donors, with an intraclass correlation coefficient ρ=0.55, than between RBC units (ρ=0.028). Therefore, in vitro testing of hemolysis potential should be against a large panel of sera to capture the inherent person-to-person variability. Hemolysis of ABO Incompatible Mixtures of RBC and Sera Phenotype Hemolysis (%) Hb (mg/dL) Visual Lysis RBC Serum N Mean±SE (min-max) p Mean±SE (min-max) > 56 mg/dL (p<0.0001) A1 O 686 6.2±0.2 (0–33.4) <0.0001 264±10 (0–1276) 526/686 (77%) A1 B 79 3.3±0.5 (0–14.9) 0.0057 142±20 (0–570) 43/79 (54%) A2 O 178 2.5±0.3 (0–17.5) 0.0011 113±13 (0–790) 70/178 (39%) A2 B 9 1.3±0.6 (0–5.2 0.5160 60±28 (0–236) 3/9 (33%)
40
Romeo, Azzurra Anna, Anna Chierichini, Diana Giannarelli, Alessandra Spagnoli, Barbara Anaclerico, Mariangela Vittori, Michele Vacca, et al. "Standard Versus High Dose Lenograstim in Adults with Hematological Malignancies for Peripheral Blood Progenitor Cell Mobilization: Results of a Retrospective Study on Behalf of Rome Transplant Network." Blood 112, no. 11 (November 16, 2008): 2302. http://dx.doi.org/10.1182/blood.v112.11.2302.2302.
Анотація:
Abstract PURPOSE: The aim of this retrospective study was to compare 5 vs 10 mcg/kg/day of lenograstim (Leno) (Myelostim 34®) in collecting target dose of CD34+ peripheral blood progenitor cells (PBPC) in adults candidate to autologous transplant. Univariate and multivariate analysis were carried out in order to identify factors predicting for satisfactory procedures. Material and Methods: From 01/’04 to 06/’08, 166 consecutive patients from 2 Institutions participating to the Rome Transplant Network with acute leukemias in complete remission (AL, #28), lymphomas (#77) and multiple myeloma (MM, #61) underwent 182 CD34+ PBPC mobilization procedures with Leno following standardized regimens. Only the 1st procedure for each patient was considered for the analysis. The target dose of CD34+ cells was ≥ 2 x106/kg for AL, ≥ 4 for lymphomas and ≥ 8 for MM with Leno starting at day +19, +1 and +5 from the end of chemotherapy, respectively. Eighty-seven patients received 5 mcg/kg Leno subcutaneously once a day (Leno5 cohort), while 79 patients were given Leno twice a day for a total dose of 10 mcg/kg (Leno10 cohort). Quantitative variables were compared by using analysis of variance (ANOVA); for qualitative parameters we used the chi-square test. A multivariate logistic model was used to analyze associations between some baseline characteristics and effectiveness to reach the required CD34+ cell target dose. Linear analysis was used to determine the relative significance of the same characteristics as predictive variables for stimulation length. Enter and remove limits were p=0.10 and 0.15, respectively. The SPSS (13.0) statistical program was used for analysis. Results: Age, sex, diagnosis and relative target dose, previous therapy including fludarabine, radiotherapy, number of previous chemotherapy regimens were not significantly different between the 2 cohorts. No statistically significant difference was observed in terms of number of apheresis performed, amount of blood processed, total number of CD34+ PBPC x103/mL mobilized and CD34+ cells x106/kg collected between the 2 cohorts. Reaching of the target dose and stimulation length are reported in table by Leno dose administered. # reaching the target Mean days ±SD Diagnosis CD34 + cell target x106/kg Leno5 Leno10 p Leno5 Leno10 p AL ≥ 2 14/19 (74%) 5/9 (56%) ns 11.2 ±6.4 6.2 ±3.1 0.035 Lymphomas ≥ 4 25/37 (68%) 33/40 (83%) ns 9.3 ±2.4 9.7 ±1.8 ns MM ≥ 8 21/31 (68%) 27/30 (90%) 0.034 8.7 ±2 7.6 ±1.8 0.033 Total 60/87 (69%) 65/79 (82%) 0.047 9.5 ±3.6 8.5 ±2.3 0.038 Forty-one patients did not reach the cell target. Of these, 16 underwent in any case PBPC transplant with the CD34+ cell dose collected. Of the remaining 25 patients, 9 were excluded from further attempts of PBPC mobilization, while 16 underwent 1 or 2 additional procedures and 10 of them were later transplanted. Overall, of 166 patients, 151 [Leno5 #76 (87%), Leno10 #75 (95%); p=ns] were able to be submitted to transplant. No Leno-related adverse event was observed in both the patient cohorts. In multivariate analysis, factors predicting for reaching the required CD34+ cell target dose were sex, with a negative impact of female sex (p=0.028), and Leno dose, with a positive impact of high dose, although exclusively restricted to MM patients (p=0.05). Finally, the multivariate analysis identified previous therapy not including fludarabine as the only factor significantly correlated with a shorter stimulation length (p=0.002). Conclusion: High dose Leno showed a higher capacity of harvesting only in MM patients for whom the CD34+ cell target was the highest to be collected. Leno dose did not impact on the CD34+ cell collection for AL and lymphoma patients as well as on the proportion of autologous transplants finally performed. As previously reported in healthy donors, in our study patient sex was an independent predictive factor for reaching the required CD34+ cell dose. Finally, fludarabine negatively influenced the length of Leno administration.
41
van der Vorst, Maurice JDL, Theresia M. Westers, Martine ED Chamuleau, Corien Eeltink, Gert J. Ossenkoppele, and Arjan A. van de Loosdrecht. "Aberrant Phenotype of blasts in Low and Intermediate-1 Risk Myelodysplastic syndromes Predicts Response of Growth Factor Treatment. a Prospective clinical Phase-II Study." Blood 112, no. 11 (November 16, 2008): 1660. http://dx.doi.org/10.1182/blood.v112.11.1660.1660.
Анотація:
Abstract Erythropoietin (Epo) and G-CSF is standard treatment for patients with low and intermediate risk-I myelodysplastic syndromes (MDS) with low Epo levels and transfusion need. Recently, it was demonstrated that flow cytometry adds significantly in the distinction of clinically relevant subgroups in MDS with respect to transfusion dependency and progressive disease. (Van de Loosdrecht et al., Blood 2008, 111) We report a prospective clinical study of 48 patients with low and intermediate-I risk MDS treated with a standardized Epo/G-CSF regimen to address the question whether flow cytometric analysis was instrumental in predicting response. All patients started with Epo if symptomatic at a Hb of less than 6.2 mmol/l independent of endogenous erythropoietin level. Epo (NeoRecormon®) was started at a dose of 30.000U once weekly. In the absence of an increase in Hb of at least 0.6mmol/l within 6 weeks, Epo was escalated to 60.000U/weekly. If still no response was achieved, G-CSF was added (3 times weekly; dose dependent on weight). Hematological response was evaluated according to IWG2006 response criteria. (Cheson, et al. Blood,2006, 108) All patients were scheduled to Epo 60.000U/week and additional G-CSF was dosed in 46 patients. From these patients 17/48 (35%) responded to the standardized Epo/G-CSF regimen. Patients with a low IPSS (0, n=25) showed hematological improvement (HI) in 44% of the cases. Patients with intermediate-I risk MDS (0.5–1.0, n=22) showed a HI in 32% of the cases. When the WHO classification-based prognostic scoring system (WPSS) was used to classify patients into subgroups (Malcovati et al., J Clin Oncol 2007, 25), 43% of the patients with a very low WPSS score (0, n=7) responded to treatment, whereas 67% in the low WPSS (1, n=21) and none in the intermediate and high risk WPSS group (2 or 3, n=20). The levels of endogenous Epo significantly discriminated between responders and non responders (p=0.003). When a cut off of 100U/l was used, 14 of the 22 patients (64%) with an Epo level below 100U/l were responsive to Epo/G-CSF treatment with a median time to response of 11 months (SD 6 mo.); 23/26 patients with high Epo levels were non responsive/Epo levels correctly predicted response to treatment in 77% of the cases (37/48, p<0.001). Strikingly, aberrancies within the myeloid blasts compartment (defined by flow cytometry as CD45dimCD34+SSClow) were mainly seen in non-responding patients (22/31 non responders, 71%). Observed aberrancies were the expression of a lineage infidelity marker (CD5, CD7 or CD56) or a loss of the myeloid antigen CD33. Only 1 out of 17 patients that responded to treatment (6%) showed an aberrant phenotype (CD7); however, response duration in this particular patient was only 4 months as compared to a median time of 12 months in the other cases. The presence of flow cytometric aberrancies correctly predicted response to treatment in 79% of the cases (38/48 cases, p<0.001). None of the responders had both a high Epo level and flow cytometric aberrancies, whereas 3 responsive patients had a relatively high Epo level without flow cytometric aberrancies. Combining Epo levels and flow cytometric aberrancies increased correct prediction of response to therapy to 85%. In 5/8 (63%) of non responders with low Epo levels an aberrant phenotype was observed. Thus, when the presence of flow cytometric aberrancies is taken into account, it may prevent needless treatment with Epo in this group. To conclude, flow cytometry may add significantly to the well known validated predictive parameters for response to select patients who are likely to respond to Epo/G-CSF. The role of flow cytometry in prediction of response to new drugs such as lenalidomide in low/int-I risk MDS is currently under investigation.
42
Donato, Eva Ma, Rafa Andreu, Aurelio Lopez, Ana Vicente, Ana Carral, Isidro Jarque, M. Angeles Ruiz, et al. "A Retrospective Population-Based Study of a Series of 307 Treatment-naïve Patients with Chronic Lymphocytic Leukemia (CLL): Study of the Clinical Features and Efficacy of First-Line Therapy." Blood 116, no. 21 (November 19, 2010): 2452. http://dx.doi.org/10.1182/blood.v116.21.2452.2452.
Анотація:
Abstract Abstract 2452 Background. Clinical trials have shown an improved response rate and progression free survival (PFS) among the different treatment options used in the last two decades, specially with rituximab in combination with fludarabine and cyclophosphamide. We wished to analyze, in an unselected community based population, the clinical characteristics and efficacy of first line therapy with several treatment options used throughout a ten-year period. Patients and methods. We included 307 patients diagnosed of CLL and requiring first-line treatment between January 2000 and September 2009. Patients were treated at 20 hospitals placed in the Community of Valencia and Murcia and received first-line therapy according to the clinical guidelines of each hospital. PFS was calculated from date of first treatment to date of progression/relapse. We performed a descriptive analysis of clinical and biological features. The survival curves were built with Kaplan-Meier method and compared with the log rank test. Multivariate analysis for response and PFS were performed by logistic and Cox regression methods respectively, using the statistical package SPSS (v15). Results. Median age at treatment was 67 years (range 28–94) with 58% (n=179) men. 39% (120/305) were in Binet A, 38% (117) in Binet B and 22% (68) in Binet C. 27% (84) were Rai III-IV. B symptoms were present in 25% (77) and fever was a rare symptom 3%. Patients were asymptomatic in 59% (181) of the cases with ECOG performance status 0–1 in 83% (256). Splenomegaly was present in 41% (127) and hepatomegaly only in 8% (24). 42% of the patients (129) had at least three lymph-node areas affected with bulky disease (diameter higher than >5cm) in 10% (32). Median haemoglobin level was 126gr/L (46–169), lymphocyte count 49 x109/L (0,5–613) with lymphocyte doubling time (LDT) <12 months in 43%. LDH was elevated in 34% (95/284) and b2-microglobulin levels in 61% (154/251). CD38 expression was positive in 42% (107/255) and ZAP-70 in 75% (91/122). The overall incidence of trysomy 12, 13q, 11q23 and 17p deletions detected by FISH were 17%, 15%, 12% and 5% respectively. Median follow-up was 33.5 months (0.6–156). First line treatment schedules and treatment response in every group are detailed in table 1. Patients receiving rituximab (group 3–4, n=73) achieved a significant higher response rate (CR or PR) than patients without rituximab (93% vs 61%). The main clinical variables with prognosis significance in the univariate analysis for PFS were: lymphocyte count (p=0,026, HR 1.002, CI95% (1.000–1.004)); haemoglobin level (p=0,02, HR 0.890, CI95% (0.826–0.958); b2-microglobulin (p=0,002, HR 1.372, CI95% (1.125–1.672)); bulky mass (p=0,055, HR 1.656, CI95% (0.989–2.775)); CD38 expression (p=0,045, HR 1.005, CI95% (1.000–1.011)); p53 deletion (p=0,014, HR 2,231, CI95% (1,180–4,217)) and 11q23 deletion (p=0,03, HR 2,138, CI95% (1,290–3,542)). The median PFS for patients in the different groups were: G1:26.9 months (22.4–31.3), G2 45.5 months (32.7–58.4), G3: not reached, G4: 20.5 months (29.6–47.3), p < 0.0001. In the multivariate analysis the variables with independent prognostic significance for PFS were: lymphocyte count (p=0.003, HR 1.004, CI 95% (1.001 −1.007)), 17deletion (p=0.01, HR 2.7 CI95% (1.273–5.73)), 11q deletion (p=0.006, HR 2.193 CI95% (1.248–3.852)) and treatment received (G1 as reference): G2 (p=0.005, HR 0.464, CI95% (0.271–0.794)), G3 (p < 0.001, HR 0.179, CI95% (0.083–0.386)), G4 (p=0.223, HR 0.289, CI95% (0.039–2.130)). Conclusion. In this community based population, treatment with rituximab containing regimens results in a higher global and complete response rate and a longer PFS compared with alquilating agents and purine analogs. Fludarabine containing-schedules also achieved a significant higher response rate than alquilating agents. Rituximab in combination with purine analogs provide the better quality of response. These results confirm the data provided by clinical trials and support their use as front-line treatment. Disclosures: Terol: ROCHE: Consultancy.
43
Seven, S., M. Ǿstergaard, L. Morsel-Carlsen, I. J. Sørensen, B. Bonde, G. Thamsborg, J. J. Lykkegaard, and S. Juhl Pedersen. "THU0541 ANATOMICAL LOCATION OF SACROILIAC JOINT MRI LESIONS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS, POSTPARTUM WOMEN, PATIENTS WITH DISC HERNIATION, CLEANING STAFF, RUNNERS AND HEALTHY PERSONS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 510–11. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2736.
Анотація:
Background:Bone marrow edema (BME) on sacroiliac joint (SIJ) MRI is central in the Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (axSpA). However, BME can be seen in other conditions and healthy persons. The presence of structural lesions may contribute to diagnosing axSpA.Objectives:To investigate the location and distribution of SIJ MRI lesions in patients with axSpA and disc herniation, women with and without post-partum pain (PPP), cleaning staff, runners, and healthy persons.Methods:In a prospective cross-sectional study of 204 participants, MRI of the SIJs was evaluated by two readers. MRI images were scored according to the SPARCC SIJ Inflammation1and Structural (SSS)2lesion definitions. Based on concordant reads, lesions were analysed according to location (unilateral/bilateral SIJ, upper/lower sacral/iliac quadrant/joint half, anterior (slice1-3)/central (slice 4-6)/posterior (slice 7-9) SIJ sections.Results:BME was present in nearly all groups, in all quadrants, and primarily in the anterior SIJ section (Figure 1), but rarely as a bilateral feature, except in axSpA and women with PPP (Table 1). Fat lesion (FAT) was mainly found in axSpA, in all slices, and mostly bilaterally in the sacrum. In the other groups FAT was primarily located in the anterior and central SIJ sections. Sclerosis was only seen in the ilium, and was present in most groups, particularly in women with PPP, often bilaterally. Erosion was only seen in women with PPP (mostly unilaterally) and in axSpA (mainly bilaterally in the ilium). Backfill and ankylosis were only seen in axSpA.Table 1.Participant characteristics and distribution of lesions – unilaterally/bilaterally in iliac/sacral quadrantsAxSpAWomen with post-partum painWomen without post-partum painDisc herniationCleaning staffLong distancerunnersHealthy menNumber of participants41461425262329Age30.9 (6.4)32.6 (3.3)*33.1 (4.1)35.2 (5.7)**39.1 (4.6)***32.7 (6.2)30.9 (6.4)Male sex630***0***440***78100***Low back pain VAS (0-10)3.8 (2.8)5.5 (2.4)**0.4 (0.7)***5.5 (2.4)*0.8 (1.8)***0.2 (0.5)***0.1 (0.3)***HLA-B27 positive8111***7***0***0***4***14***C-Reactive Protein >3 mg/l5917***21**20**15**17**3***Quadrant:UNI / BIUNI / BIUNI / BIUNI / BIUNI / BIUNI / BIUNI / BIBMEIliumUpperLower27 / 722 / 1711 / 915 / 130 / 021 / 00 / 00 / 00 / 40 / 40 / 04 / 00 / 00 / 0SacrumUpperLower29 / 2224 / 2017 / 99 / 929 / 04 / 04 / 04 / 04 / 00 / 00 / 00 / 00 / 00 / 0FATIliumUpperLower20 / 1717 / 292 / 00 / 07 / 07 / 04 / 04 / 00 / 00 / 00 / 00 / 00 / 70 / 3SacrumUpperLower22 / 4417 / 422 / 42 / 20 / 74 / 70 / 40 / 00 / 00 / 04 / 04 / 03 / 33 / 3SclerosisIliumUpperLower5 / 20 / 04 / 49 / 90 / 77 / 04 / 40 / 44 /415 / 00 / 04 / 03 / 70 / 0SacrumUpperLower0 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 0ErosionIliumUpperLower22 / 2417 / 244 / 02 / 20 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 0SacrumUpperLower10 / 522 / 22 / 02 / 20 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 00 / 0Values are % or mean (SD)Mann-Whitney test was applied, tests are patients with axSpA compared with all other groups. P<0.05*; p<0.01**; p<0.001***BI: bilateral; BME: Bone marrow edema; FAT: fat lesion; HLA-B27: Human Leukocyte Antigen B27;UNI: unilateral; VAS: Visual Analogue scaleConclusion:Typical locations of common SIJ lesions in axSpA and non-axSpA were reported. In non-axSpA, except women with PPP, bilateral as well as posterior lesions were rare, while backfill and ankylosis were absent.References:[1]Maksymowych et al,Arthritis Rheum, 2005[2]Maksymowych et al,J of Rheumatol,2015Acknowledgments:Disclosure of Interests: Sengül Seven Grant/research support from: Novartis, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Lone Morsel-Carlsen: None declared, Inge Juul Sørensen: None declared, Birthe Bonde: None declared, Gorm Thamsborg: None declared, Jens Jørgen Lykkegaard: None declared, Susanne Juhl Pedersen Grant/research support from: Novartis
44
Proft, F., J. Schally, H. C. Brandt, J. Brandt-Juergens, G. R. Burmester, H. Haibel, H. Käding, et al. "POS0241 VALIDATION OF THE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE WITH A QUICK QUANTITATIVE C-REACTIVE PROTEIN ASSAY (ASDAS-QCRP) IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS (AXSPA): A PROSPECTIVE, NATIONAL, MULTICENTER STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 342.1–342. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2352.
Анотація:
Background:According to international recommendations, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred score for assessing disease activity in axial spondyloarthritis (axSpA) [1]. However, routine determination of C-reactive protein (CRP) to calculate ASDAS values takes hours to days. This limits the use of ASDAS in clinical routine and clinical trials and hinders the implementation of treat-to-target approaches in axSpA. Whereas quick quantitative CRP (qCRP) tests allow CRP assessment within a few minutes. In a pilot project the performance of qCRP-based ASDAS assessment (ASDAS-qCRP) was already investigated in a single center study of 50 newly diagnosed, bDMARD-naïve axSpA patients with promising results [2].Objectives:To validate the ASDAS-qCRP in a prospective, multicenter study of axSpA patients in a typical axSpA cohort with an appropriate sample size.Methods:The study was conducted in five centers in Germany. Consecutive adult (≥ 18 years) axSpA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for ASDAS-CRP and ASDAS-qCRP.Results:In this study 251 axSpA patients were included between January and September 2020 (mean age: 38.4 years; mean disease duration: 6.2 years, 159 patients (63.3%) were male, 211 (84.1%) HLA-B27 positive and 195 (77.7%) were classified as radiographic axSpA). 143 patients (57.0%) were treated with bDMARDs. CRP and qCRP showed mean values of 2.12 and 2.17 mg/l, respectively. With the ASDAS-qCRP, 242 patients (96.4%) were assigned to the same disease activity category as compared to the ASDAS based on the conventional lab CRP measurement (Table 1). Weighted Cohen´s kappa was 0.966 (95%CI: 0.943; 0.988). ICC for ASDAS-CRP- and ASDAS-qCRP-values was 0.997 (95%CI: 0.994; 0.999). The agreement of ASDAS-qCRP and ASDAS-CRP is shown in a Bland-Altman plot (Figure 1).Table 1.Disease activity categories by ASDAS-qCRP vs. ASDAS-CRPASDAS-qCRP (n = 251)Inactive Disease(< 1.3)Low Disease Activity (1.3 - < 2.1)High Disease Activity (2.1 - 3.5)Very high Disease Activity (> 3.5)ASDAS-CRPInactive Disease(< 1.3)56 (22.3%)2 (0.8%)Low Disease Activity (1.3 - < 2.1)62 (24.7%)7 (2.8%)High Disease Activity (2.1 - 3.5)97 (38.6%)Very high Disease Activity (> 3.5)27 (10.8%)The fields highlighted in red indicate that disease activity categories do not match.ASDAS = Ankylosing Spondylitis Disease Activity Score, CRP = C-reactive protein, qCRP = quick quantitative CRPConclusion:The ASDAS-qCRP and ASDAS-CRP showed an almost perfect agreement on the assignment to disease activity categories (96%) with the important advantage of time. With ASDAS-qCRP, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. ASDAS-qCRP, therefore, can be integrated in clinical routine and clinical trials in the future and may facilitate implementation of the treat-to-target concept in axial SpA.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.[2]Proft F, et al. Joint Bone Spine. 2019 Jul 29.Figure 1.Bland-Altman plot for ASDAS-qCRP and ASDAS-CRPAcknowledgements:The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study.Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland.Disclosure of Interests:None declared
45
Зайнулгабидинов, Эрик Ренатович, Юрий Алексеевич Игнатьев та Андрей Михайлович Петров. "ВЛИЯНИЕ ФИТОРЕМЕДИАЦИИ НА ПРОФИЛЬ УГЛЕВОДОРОДОВ НЕФТИ В АЛЛЮВИАЛЬНЫХ ДЕРНОВЫХ ПОЧВАХ". Российский журнал прикладной экологии, № 2 (25 червня 2021): 53–60. http://dx.doi.org/10.24852/2411-7374.2021.2.53.60.
Анотація:
Фиторекультивация почв, загрязненных нефтью и нефтепродуктами, рассматривается как один из перспективных подходов в биотехнологии. Эффективность этого метода зависит от под- бора культур. Объектом исследования являлась загрязненная нефтью аллювиальная дерновая легкосуглинистая почва. Рассматривались варианты с начальным содержанием нефти 5.4 г/кг, 9.7 г/кг и 21.8 г/кг. В качестве фиторемедиантов использовались однодольные и двудольные растения ‒ пшеница яровая (Triticum vulgare L.) и горох посевной (Pisum sativum L). Газохроматографическим методом изучено изменение углеводородного состава после фиторекультивационных мероприятий. На хроматограммах идентифицированы пики гомологов н-алканов диапазона С9‒С36 и углеводороды (УВ) неполярного и малополярного строения, образующие «изопреноидный горб». Стимулируя активность микроорганизмов в прикорневой зоне, рассматриваемые культурыоказывают различное влияние на деструкцию и преобразование остаточной нефти в зависимости от степени загрязнения. Существенное снижение концентрации УВ нефти к концу эксперимента (в 3.8 раза) отмечено в варианте с максимальным содержанием поллютанта в опыте с пшеницей. Отмечается обратная зависимость процентного содержания н-алканов от уровня остаточного содержания нефтепродуктов. Выделено 2 типа распределения неполярных УВ. Для вариантов с низким уровнем загрязнения характерна мономодальная форма. Второй тип имел бимодальное распределение и был типичен для опытных образцов с относительно высокой концентрацией. Профиль н-алканов характеризовался преобладанием четных гомологов в среднемолекулярной области. Полученные данные могут указывать, что наиболее вероятными продуцентами четных парафинов среднемолекулярного диапазона может быть биомасса микробиоты.
Библиографические ссылки
1. Габов Д.Н., Безносиков В.А., Кондратенок Б.М., Грузлев И.В. Насыщенные углеводороды в фоновых и загрязненных почвах Предуралья // Почвоведение. 2010. №10. С. 1190‒1196.
2. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М., Хабибуллин Р.Э. Особенности распределения нормальных алканов в современных дерново-подзолистых почвах // Вестник технологического университета. 2015. Т.18, №4. С. 271‒274.
3. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М., Хабибуллин Р.Э. Влияние длительности инкубации на состав нормальных углеводородов при разных уровнях начального содержания нефти в почве // Вестник технологическогоуниверситета. 2016. Т. 19, №10. С. 56‒60.
4. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М. Оптимизация метода потери массы при прокаливании для определения остаточного содержания органических соединений нефти в загрязненных почвах // Российский журнал прикладной экологии. 2021. №1. С. 64‒71.
5. Игнатьев Ю.А., Зайнулгабидинов Э.Р., Петров А.М. Изменение углеводородного состава нефтезагрязнённой дёрново-подзолистой почвы в стандартизированных условиях инкубации // Вестник технологического университета. 2014. Т. 17, №15. С. 256‒260.
6. Игнатьев Ю.А., Зайнулгабидинов Э.Р., Петров А.М. Применение метода прокаливания для определения содержания аллохтонных углеводородов нефти в почвах // Российский журнал прикладной экологии. 2018. №3. С. 34‒37.
7. Кальвин М. Химическая эволюция. М.: Мир, 1971. 283 с.
8. Каримуллин Л.К., Петров А.М., Вершинин А.А. Фиторекультивация и физиологическая активность нефтезагрязненной дерново-подзолистой почвы // Российский журнал прикладной экологии. 2016. №1. С. 14‒17.
9. Киреева Н.А., Водопьянов В.В. Мониторинг растений, используемых для фиторемедиации нефтезагрязненных почв // Экология и промышленность России. 2007. №9. С. 46‒47.
10. Киреева Н.А., Новоселова Е.И., Шамаева А.А., Григориади А.С. Биологическая активность чернозема выщелоченного, загрязненного продуктами сгорания попутного нефтяного газа, и возможности ее восстановления при фиторемедиации // Почвоведение. 2009. №4. С. 498‒503.
11. Киреева Н.А., Новоселова Е.И., Григориади А.С. Влияние загрязнения почв нефтью на физиологические показатели растений и ризосферную микробиоту // Агрохимия. 2009а. №7. С. 71‒80.
12. Киреева Н.А., Григориади А.С., Водопьянов В.В., Амирова А.Р. Подбор растений для фиторемедиации почв, загрязненных нефтяными углеводородами // Известия Самарского научного центра РАН. 2011. Т. 13, №5. С. 184‒187.
13. Киреева Н.А., Григориади А.С., Баширова Р.М., Ами-рова А.Р. Использование бархатцев прямостоячих Tagetes erecta L. для фиторемедиации почвы, загрязненной нефтяными углеводородами // Агрохимия. 2012. №5. С. 66–72.
14. Муратова А.Ю., Бондаренкова А.Д., Панченко Л.В., Турковская О.В. Использование комплексной фиторемедиации для очистки почвы, загрязненной нефтешламом // Биотехнология. 2010. №1. С. 77‒84.
15. Пахарькова Н.В., Прудкова С.В., Гекк А.С., Ларькова А.Н., Коростелева Н.С. Оптимизация выбора растений для биоремедиации почв, загрязненных нефтью и нефтепродуктами в условиях южной Сибири // Вестник КрасГАУ. Биологические науки. 2015. №8. С. 28‒32.
16. Петров А.А. Углеводороды нефти. М.: Наука, 1984. 264 с.
17. Утомбаева А.А., Петров А.М., Зайнулгабидинов Э.Р., Игнатьев Ю.А., Кузнецова Т.В. Динамика роста высших растений на рекультивированных нефтезагрязненных аллювиальных луговых почвах разного гранулометрического состава // Российский журнал прикладной экологии. 2020. №1. С. 60‒65.
18. Фатина П.Н., Лапаева И.В., Давыдова Е.А. Фиторемедиация – эффективный и экономический метод очистки почвы, загрязненной нефтью и нефтепродуктами // Защита окружающей среды в нефтегазовом комплексе. 2008. №5. С. 75‒78.
19. Eglinton G., Hamilton R.J. Leaf epicuticular waxes // Science. 1967. V. 56. P. 1322‒1335.
20. Ekpo B.O., Oyo-Ita O.E., Wehner H. Even-n-alkane/ alkene predominances in surface sediment from the Calabar River, SE Niger Delta, Nigeria // Naturwissenschaften. 2005. V. 92. Р. 341–346. DOI 10.1007/s00114-005-0639-8.
21. Marseille F., Disnar J.R., Guillet B., Noack Y. n-Alkanes and free fatty acids in humus and A1 horizon of soils under beech, spruce and grass in the Massif-Central (Mont-Loze Áre), France // European journal of soil science. 1999. V. 50. P. 433- 441. htpps://doi.org/10.1046/j.1365-2389.1999.00243.x
22. Jovančićević B., Vrvić M., Schwarzbauer J., Wehner H., Scheeder G., Vitorović D. Organic-geochemical differentiation of petroleum-type pollutants and study of their fate in Danube alluvial sediments and corresponding water (Pančevo Oil Refinery, Serbia) // Water, air soil pollution. 2007. V. 183. P. 225–238. DOI: 10.1007/s11270-007-9371-7
23. Jovančićević B. Identification, transformation and migration of petroleum-type pollutants in recent sediments and soil // Newsletter of European association of chemistry and the environment. 2002. №3. Р. 5–6.
24. Lei G.L., Zhang H.C., Chang F.Q., Pu Y., Zhu Y., Yang M.S., Zhang W.X. Biomarkers of modern plants and soils from Xinglong Mountain in the transitional area between the Tibetan and Loess Plateaus // Quaternary international. 2010. V. 218. P. 143–150. htpps://doi.org/10.1016/j.quaint.2009.12.009
25. Rao Z.G., Zhu Z.Y., Jia G.D., Zhang X., Wang S.P. Compound-specific hydrogen isotopes of long-chain n-alkanes extracted from topsoil under a grassland ecosystem in northern China // Science in China. Ser. D: Earth Sciences. 2011. V. 54, №12. P. 1902‒1911. htpps://doi.org/10.1007/s11430-011-4252-8
26. Wang Y., Fang X., Bai Y., Xi X., Zhang X., Wang Y. Distribution of lipids in modern soils from various regions with continuous climate (moisture-heat) change in China and their climate significance // Science in China. Ser. D.: Earth Sciences. 2007. V. 50, №4. Р. 600‒612. htpps://doi.org/10.1007/s11430-007-2062-9.
46
Saini, Lalit, Robert Turner, Loree Larratt, Joseph Brandwein, Marlene Ann Hamilton, Anthea Peters, Cynthia M. Wu, et al. "Bone Marrow Aspirates Alone without a Trephine Biopsy May be Insufficient for the Detection of Residual Leukemia Following Intensive Chemotherapy for the Treatment of Acute Myeloid Leukemia." Blood 124, no. 21 (December 6, 2014): 2336. http://dx.doi.org/10.1182/blood.v124.21.2336.2336.
Анотація:
Abstract Background: The diagnosis of acute myeloid leukemia (AML), response to treatment and disease recurrence are most commonly assessed with bone marrow studies. Recommendations from leading experts (Bain, 2001) and guidelines of the European LeukemiaNET (Dohner, 2010) and the National Comprehensive Cancer network (O’Donnell, 2012) suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease while the trephine biopsy (TB) is necessary only when an aparticulate BMA is obtained. In contrast, guidelines of the International Council for Standardization in Hematology (Lee, 2008) suggest that BMA and the TB should be routinely performed together as they provide complementary information. Due to these conflicting recommendations we sought to determine whether the TB provides additional sensitivity for the detection of residual leukemia following intensive chemotherapy for AML. Methods: A single centre retrospective chart review was conducted of bone marrow studies of all AML patients who had received intensive chemotherapy from 2004 – 2013. Those lacking a TB were excluded. Residual disease was assessed by morphological examination of the BMA and TB +/- immunostaining but minimal residual disease (MRD) analysis was not performed. Results: 598 bone marrow studies from 227 patients were evaluated. The median age of the patients was 54.6 (range 18 -77) with 70% age < 60. Forty-four percent were female. Cytogenetics were favorable in 30 (13%), intermediate in 146 (64%), high-risk in 44 (19%) and failed in 7 (3%) of the patients. Of the 598 bone marrow samples 198 (33%) were interim marrows performed 14 days following initiation of induction or re-induction chemotherapy (D14 marrow), 251(42%) were recovery marrows following induction/re-induction chemotherapy (EOI marrow) and 149 (25%) were during follow-up. The BMA was considered to be acellular/hypocellular in 31%, hemodilute in 16.4% and aparticulate/pauciparticulate in 27.3% of samples. As per guidelines > 200 cells were counted in 99.8% of the aspirate samples to ascertain remission status. The median length of the TB segments was 1.85 cm (0.2 – 7.0 cm) and it was considered inadequate in 12.7%, of good or excellent quality in 24.9% and adequate for residual disease assessment in the remainder of cases. Approximately 19 % of TB samples had mild to significant hemorrhagic artifact. The bone marrow cellularity could not be assessed in 1.2% of samples but was patchy in 0.5%, aplastic in 2.8%, hypocellular in 36%, normocellular in 23.6%, hypercellular in 23.2%, packed in 6% and was not described in 6.7% of the cases. Residual leukemia was identified in 33.1% of BMA and in 33.3% of TB samples. The BMA and the TB findings were concordant in 562 of 598 (94%) of cases. In 3.5% (21) of cases residual leukemia was seen in the TB but not the BMA whereas in 2.5% (15) of cases the BMA detected residual disease but the TB failed to do so. The TB led to a change in diagnosis from ‘No Leukemia’ to ‘Residual Disease’ in 5.1% of D14 marrows, 3.6% of EOI marrows and in 1.3% of follow-up marrows with no statistically significant difference between the groups (p=0.178). There was no relationship between a change in diagnosis and whether patients received an anthracycline or a non-anthracycline based chemotherapy regimen (4.4% vs. 3.2%, p=1.0). The TB, however, led to a change in diagnosis more commonly in patients with favorable risk karyotype relative to those with intermediate risk karyotype (20% vs. 6.2%, p= 0.02) but not relative to those with unfavorable risk karyotype (20% vs. 13.6%, p=0.53). Hemodilute bone marrow samples were more likely to have a TB related change in diagnosis relative to undilute samples (8.2% versus 2.6%, p=0.01) as were aparticulate/pauciparticulate samples relative to particulate samples (8% vs. 1.9%, p=0.00046). However, in multivariate analysis, only an aparticulate/pauciparticulate sample was associated with TB related change in diagnosis (p=0.015, OR = 3.6). Conclusions: Our data demonstrate that, following intensive chemotherapy, the BMA alone may fail to identify residual leukemia particularly when the BMA is aparticulate/pauciparticulate. In these situations the TB provides additional sensitivity for the detection of residual disease. Further studies are required to evaluate the need for the TB in particulate samples when combined with MRD analysis. Disclosures No relevant conflicts of interest to declare.
47
Schnyder, J., J. Monahan, W. Smith, H. Hope, D. Kelly, D. Burt, E. Huff, et al. "SAT0143 A PHASE 1 STUDY IN HEALTHY VOLUNTEERS EXPLORING THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ATI-450: A NOVEL ORAL MK2 INHIBITOR." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1010.2–1010. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5645.
Анотація:
Background:ATI-450, is an investigational small molecule inhibitor of the MAPK-activated protein kinase 2 (MK2) signaling pathway. This pathway drives the expression of multiple cytokines including TNFα, IL-1α and β, and IL-6.Objectives:We evaluated the safety and tolerability of ATI-450 in healthy volunteers as well as pharmacokinetics (PK) and pharmacodynamics (PD). Here we present data from single and multiple ascending dose cohorts. The aim was to select a dose for evaluation in phase 2 in patients with rheumatoid arthritis.Methods:Safety, PK and PD were assessed in a randomized, observer-blind, placebo-controlled, phase 1 study in male and female healthy subjects aged 18-55 (n=77).Part A: Single Ascending Dose (SAD) (n=32, 8 subjects per dose cohort - 2 placebo, 6 active). A single dose of 10mg, 30mg, 50mg and 100mg was tested.Part B: Multiple Ascending Dose (MAD) (n=30, 10 subjects per dose cohort - 2 placebo, 8 active). 10mg BID, 30mg BID and 50mg BID doses were tested over 7 days of administration.Safety and tolerability of ATI-450 was evaluated based on adverse events, clinical laboratory, vital signs, 12-lead ECG, Holter monitoring, and physical examination. Blood was drawn for PK analysis at 0.5, 1, 2, 4, 6, 8, 12 hours, 24, 36, and 48 hours post dose in the SAD cohort and on day 7 of the MAD cohort. PD of ATI-450 were explored by investigating the inhibition of a target biomarker, phospho-HSP27 (pHSP27) and proinflammatory cytokines, TNFα, IL1β, IL6 and IL8 inex-vivoLPS-stimulated blood samples collected 4 and 12 hours post dose on day 7 from subjects in the MAD cohorts.Results:ATI-450 was generally well tolerated. No serious adverse events or severe adverse events were reported, and no adverse events led to discontinuation of the study medication. The most common adverse events (reported by 2 or more subjects who received ATI-450) observed during the trial were dizziness, headache, upper respiratory tract infection, constipation, nausea, and abdominal pain. All adverse events were mild. A trend of a decrease in absolute neutrophil count (ANC) was observed without correlated clinical sequelae.ATI-450 had dose proportional PK with a terminal half-life (t½) of 9-12 hours in the MAD cohort on day 7. A dose and concentration dependent inhibition ofex vivostimulated cytokines and target biomarker was observed. On day 7, patients in the 50mg BID dose (the dose with the highest degree of inhibition) recorded mean trough drug levels (12 hours post dose) that were 1.4, 2.5, 2.5 and 2.4 times greater than the IC80for TNFα, IL1β, IL8 and pHSP27 respectively. Mean Cmax drug levels (4 hours post dose) were 3.6, 6.4, 6.2 and 6.0 times greater than the IC80for TNFα, IL1β, IL8 and pHSP27 respectively. IL6 levels were inhibited by more than 50% for part of the dosing interval.Conclusion:Oral ATI-450 was generally well tolerated at all doses with dose proportional PK. The t½ suggests that once or twice daily oral dosing may be possible. At the 50mg BID dose, marked inhibition of TNFα, IL1β and IL8, IL6 and pHSP27 was observed. ATI-450 has the potential to be an oral, small molecule drug which can target multiple cytokines. Exploration of its benefit to risk profile in patients with rheumatoid arthritis is warranted.Disclosure of Interests:Judy Schnyder Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, Joe Monahan Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, Walter Smith Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, Heidi Hope Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, Deborah Kelly Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, David Burt Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, E Huff Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, A Kaul Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, A Hildebrand Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, B Burnette Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, N Klug Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics, M Bangs Shareholder of: Aclaris Therapeutics, Employee of: Aclaris Therapeutics, David Gordon Shareholder of: aclaris therapeutics, Employee of: aclaris therapeutics
48
Estrella, Soledad, and Patricia Estrella. "Representaciones de datos en estadística: de listas a tablas." Revista Chilena de Educación Matemática 12, no. 1 (April 20, 2020): 21–34. http://dx.doi.org/10.46219/rechiem.v12i1.20.
Анотація:
Con el propósito de estudiar la organización de datos e identificar la diversidad de representaciones construidas en situación de exploración de datos auténticos, en un grupo de 56 estudiantes chilenos de tercer grado de primaria, se diseñó e implementó un plan de clases de estadística, en el que se solicitó a los estudiantes ordenar y organizar los datos para responder a un problema. Este artículo se centra en el estudio cualitativo de las representaciones de datos producidas por los estudiantes durante la implementación del plan de clases. La exploración de los datos realizada por los estudiantes sobre los alimentos que consumían en la escuela (“colaciones”), los llevó a elaborar representaciones de datos (listas, estado intermedio de esquema tabular y tabla de frecuencias). Se concluye que el contexto auténtico y la construcción de representaciones propias promovieron que los estudiantes construyeran preponderantemente listas (77%), aplicando con sentido la partición, la clase y el cardinal. Se sugiere incorporar explícitamente en la enseñanza el formato lista, como herramienta representacional y unidad básica de la tabla. Referencias Brizuela, B., y Alvarado, M. (2010). First graders' work on additive problems with the use of different notational tools. Revista IRICE, 21, 37-43. Recuperado a partir desde https://ojs.rosario-conicet.gov.ar/index.php/revistairice/article/view/v21n21a04 Brizuela, B., y Lara-Roth, S. (2002). Additive relations and function tables. Journal of Mathematical Behavior, 20(3), 309-319. https://doi.org/10.1016/S0732-3123(02)00076-7 Coutanson, B. (2010). La question de l’éducation statistique et de la formation de l’esprit statistique à l’école primaire en France. Étude exploratoire de quelques caractéristiques de situations inductrices d’un enseignement de la statistique au cycle III (Tesis doctoral). Université de Lyon, Francia. Recuperado desde https://tel.archives-ouvertes.fr/tel-00494338/ Dibble, E. (1997). The Interpretation of Tables and Graphs. Seattle, WA: University of Washington. Duval, R. (2003). Comment Analyser le Fonctionnement Representationnel des Tableaux et leur Diversite? Spirale -Revue de Recherches en Éducation-, 32, 7-31. Recuperado desde http://spirale-edu-revue.fr/IMG/pdf/1_Duval_Spi32F.pdf Estrella, S. (2014). El formato tabular: una revisión de literatura. Revista Actualidades Investigativas en Educación, 14(2), 1-23. Estrella, S., e Isoda, M. (2020). Suma Primero: manual del docente, 1° básico. Valparaíso: Ediciones Universitarias de Valparaíso. Estrella, S., Mena-Lorca, A., y Olfos, R. (2017). Naturaleza del objeto matemático “Tabla”. Magis: Revista Internacional de Investigación en Educación, 10(20), 105-122. https://doi.org/10.15517/aie.v14i2.14817 Estrella, S., Olfos, R., Morales, S., y Vidal-Szabó, P. (2017). Argumentaciones de estudiantes de primaria sobre representaciones externas de datos: componentes lógicas, numéricas y geométricas. Revista Latinoamericana de Investigación en Matemática Educativa, 20(3), 345-370. https://doi.org/10.12802/relime.17.2034 Estrella, S., Olfos, R., Vidal-Szabó, P., Morales, S., y Estrella, P. (2018). Competencia meta-representacional en los primeros grados: representaciones externas de datos y sus componentes. Revista Enseñanza de las Ciencias, 36(2), 143-163. https://doi.org/10.5565/rev/ensciencias.2143 Estrella, S., Zakaryan, D., Olfos, R., y Espinoza, G. (2020). How teachers learn to maintain the cognitive demand of tasks through Lesson Study. Journal of Mathematics Teacher Education, https://doi.org/10.1007/s10857-018-09423-y Friel, S. N., Curcio, F. R., y Bright, G. W. (2001). Making sense of graphs: Critical factors influencing comprehension and instructional implications. Journal for Research in Mathematics Education, 124-158. https://psycnet.apa.org/doi/10.2307/749671 Gabucio, F., Martí, E., Enfedaque, J., Gilabert, S., y Konstantinidou, A. (2010). Niveles de comprensión de las tablas en estudiantes de primaria y secundaria. Cultura y Educación, 22(2), 183-197. https://doi.org/10.1174/113564010791304528 Kaufman, E. L., Lord, M. W., Reese, T. W., y Volkmann, J. (1949). The discrimination of visual number. The American journal of psychology, 62(4), 498-525. Lehrer, R., y Schauble, L. (2000). Inventing data structures for representational purposes: Elementary grade students' classification models. Mathematical Thinking and Learning, 2(1-2), 51-74. https://psycnet.apa.org/doi/10.1207/S15327833MTL0202_3 Martí, E. (2009). Tables as cognitive tools in primary education. En C. Andersen, N. Scheuer, M. Pérez Echeverría, y E.V. Teubal (Coord.), Representational systems and practices as learning tools (pp. 133-148). Rotterdam: Sense Publishers. Martí, E., García-Mila, M., Gabucio, F., y Konstantinidou, K. (2010). The construction of a double-entry table: a study of primary and secondary school students’ difficulties. European Journal of Psychology of Education, 26(2), 215-234. www.jstor.org/stable/23883606 Martí, E., Pérez, E., y De la Cerda, C. (2010). Alfabetización gráfica. La apropiación de las tablas como instrumentos cognitivos. Contextos, 10, 65-78. Martínez, M., y Brizuela, B. (2006). A third grader’s way of thinking about linear function tables. Journal of Mathematical Behavior, 25, 285-298. https://doi.org/10.1016/j.jmathb.2006.11.003 Ministerio de Educación de Chile. (2018). Bases Curriculares Primero a Sexto Básico. Santiago de Chile: Unidad de Currículum y Evaluación, Ministerio de Educación de Chile. Recuperado desde https://www.curriculumnacional.cl/614/articles-22394_bases.pdf Moore, D. S., y Cobb, G. W. (2000). Statistics and mathematics: Tension and cooperation. The American Mathematical Monthly, 107(7), 615-630. Nisbet, S., Jones, G., Thornton, C., Langrall, C., y Mooney, E. (2003). Children’s Representation and Organisation of Data. Mathematics Education Research Journal, 15(1), 42-58. https://doi.org/10.1007/BF03217368 Pérez-Echeverría, M., y Scheuer, N. (2009). External Representations as Learning Tools: An Introduction. En C. Andersen, N. Scheuer, M. Pérez-Echeverría, y E. Teubal (Eds.), Representational systems and practices as learning tools (pp. 1-17). Rotterdam: Sense Publishers. Pfannkuch, M., y Rubick, A. (2002). An exploration of students’ statistical thinking with given data. Statistics Education Research Journal, 1(2), 4-21. https://iase-web.org/documents/SERJ/SERJ1(2).pdf Sepúlveda, A., Díaz-Levicoy, D., y Jara, D. (2018). Evaluación de la comprensión sobre Tablas Estadísticas en estudiantes de Educación Primaria. Bolema: Boletim de Educação Matemática, 32(62), 869-886. http://dx.doi.org/10.1590/1980-4415v32n62a06 Tukey, J. (1977). Exploratory data analysis. Reading, MA: Addison-Wesley. Wu, H., y Krajcik, J. (2006). Inscriptional Practices in Two Inquiry-Based Classrooms: A Case Study of Seventh Graders’ Use of Data Tables and Graphs. Journal of Research in Science Teaching, 43(1), 63-95. https://doi.org/10.1002/tea.20092 Financiamiento: Esta investigación se ha realizado dentro del proyecto subvencionado por Agencia Nacional de Investigación y Desarrollo (ANID) / FONDECYT 1200346 y Proyecto VRIE-PUCV 039.439/2020
49
Ho, Prahlad, Hui Yin Lim, Cheryl Ng, Carole L. Smith, Geoffrey Donnan, and Harshal Nandurkar. "Global Coagulation Assays in the Normal Population: Female Gender, Older Age and East Asian Ethnicity Associated with Prothrombotic Parameters." Blood 126, no. 23 (December 3, 2015): 4678. http://dx.doi.org/10.1182/blood.v126.23.4678.4678.
Анотація:
Abstract Aim Thrombotic diseases are major causes of morbidity and mortality, and yet there are currently no laboratory tests to evaluate this risk. Global coagulation assays such as thrombin generation via calibrated automated thrombogram (CAT) and thromboelastography (TEG), may be better surrogate measures of an individualÕs thrombosis risk. However, the evaluation of age, race and gender differences in the normal population is important prior to the inclusion of these assays into studies on diseased populations. Methods Normal controls with no thrombotic history and no anticoagulant/antiplatelet use were recruited. Routine tests were performed to exclude underlying risk factors including full blood count, thrombophilia screen and fasting lipids. All samples were citrated; platelet poor plasma (PPP) samples were double-centrifuged at 2500G, aliquoted and frozen at -80o C within 2 hours of collection. TEG 5000S analysis was performed within 4 hours of collection, using whole citrated blood under standard manufacturer guidelines. CAT was performed with PPP using standard commercially available (STAGO) 5 pmol reagent and flurogenic (Fluca-Kit). Results 63 normal controls (43F, 20M) with median age of 36.5 (20-75) years were recruited. None had abnormal platelet or coagulation parameters. TEG: 36 volunteers (57%) had TEG parameters outside the manufacturerÕs normal range. Females and older individuals (age >50 years) had more prothrombotic TEG parameters including increased maximum amplitude (MA), alpha-angle and derived thrombin generation; with reduced R and K time. Older females (age >50 years) also had more prothrombotic parameters compared to younger females. Clot lysis (LY30) was significantly lower in the older population with no gender differences. (Table 1) CAT: Females had higher endogenous thrombin potential (ETP), which represented the total thrombin formed, and higher velocity index. Older individuals had higher ETP but paradoxically a longer lag time. (Table 1) CAT vs TEG: There was no correlation between TEG parameters (such as MA or derived thrombin generation), and ETP via CAT (r2=0.005 and r2=0.006 respectively). Race differences: Of the 63 volunteers, 25 and 30 were of European and East Asian origin respectively. East Asians had significantly higher ETP, thrombin peak and velocity index (p<0.01), but these differences were less apparent using TEG, which also evaluated the platelet effect on clot formation. Statistically significant variation was only seen in the α-angle (p=0.04). (Table 2) Conclusion This study demonstrates that there are significant gender and age differences within the normal population. 57% of our volunteers had at least one TEG parameter outside the manufacturers reference range. Females had more prothrombotic parameters, which was independent of hormonal status. Older individuals (age >50 years) having more prothrombotic parameters, particularly clot lysis (LY30) using TEG, suggests a role of fibrinolysis in the futher evaluation of thrombotic risk. East Asians had significantly lower CAT parameters, which may explain the lower venous thrombotic risk seen in this population. Our results suggest that a localized reference range, tailored to gender, age and ethnicity is required for global coagulation assays. Table 1. Gender and age difference with TEG and CAT Male Female Age <50years Age ³50years No of controls 20 43 32 31 TEG parameters R time (min) 8.7 6.8 p <0.01 8.2 6.6 p =0.01 K time (min) 3.2 2.2 p <0.01 2.9 2.2 p =0.03 α-angle (¡) 50.6 59.8 p <0.01 52.2 61.3 p <0.01 MA (mm) 54.3 59.7 p <0.01 56.1 59.8 P=0.02 LY30 (%) 1.8 1.9 p=0.92 3.1 0.7 p <0.01 Derived Thrombin Gen 671 724 p <0.01 676 737 p <0.01 CAT parameters Lag Time (min) 3.0 3.2 p=0.53 2.8 3.4 p <0.01 ETP (nM/min) 1245 1399 p =0.03 1290 1403 p=0.06 Peak height (nM) 211 245 p=0.06 221 243 p=0.13 Vel Index (nM/min) 65 86 p =0.03 79 77 p=0.97 Time to Peak (min) 6.5 6.4 p=0.58 6.2 6.8 p=0.06 Table 2. Ethnic difference with CAT and TEG parameters Manufacturer values East Asian (n=30) European (n=25) p-value (% variation) TEG parameters R time (min) 2-8 7.8 6.8 0.15 (+14%) K time (min) 1-2 2.8 2.2 0.06 (+23%) α-angle (¡) 55-78 53.9 60.0 0.04 (-10%) MA (mm) 51-69 57.4 58.4 0.57 (-2%) Lysis time, LY30 (%) 0-8 1.9 2.4 0.53 (-34%) CAT parameters Not available Lag Time (min) 3.0 3.2 0.22 (-7%) ETP (nM/min) 1231.5 1411.7 <0.01 (-23%) Peak height (nM) 206.8 254.8 <0.01 (-19%) Vel Index (nM/min) 65.6 92.5 <0.01 (-30%) Disclosures No relevant conflicts of interest to declare.
50
Lengfelder, Eva, Francesco Lo-Coco, Pau Montesinos, David Grimwade, Lionel Ades, Bhuvan Kishore, Maria Pagoni, et al. "Treatment of Molecular and Clinical Relapse of Acute Promyelocytic Leukemia (APL) with Arsenic Trioxide: Results of the European Registry of Relapsed APL." Blood 116, no. 21 (November 19, 2010): 15. http://dx.doi.org/10.1182/blood.v116.21.15.15.
Анотація:
Abstract Abstract 15 Arsenic trioxide (ATO) is presently regarded as the best treatment option in relapsed PML-RARA+ acute promyelocytic leukemia (rAPL). However, given the relative rarity of relapses following standard front-line APL therapy, the optimal management of this group of patients remains to be firmly established. For this reason, and in order to ensure homogeneity in patient data collection and gain insights into the epidemiology and clinical aspects of rAPL, a European registry of rAPL was established in 2008 under the auspices of the European LeukemiaNet (ELN). Patients with a genetically confirmed (PML-RARA+) molecular or clinical relapse of APL occurring from January 2003 onwards were eligible for registration using uniform CRFs. Management of relapse was at the discretion of the treating physician, but could be based on the treatment recommendations developed by an expert panel provided on the ELN website (www.leukemia-net.org/content/). By 15 July 2010, 122 cases of rAPL had been registered by participants of 7 European countries (Spain, Italy, UK, France, Germany, Greece, Poland) representing the starting group of this ongoing initiative open for participation. In 80 pts (69 in first, 11 in 2nd and later relapse), information was available on ATO salvage therapy. At time of first diagnosis median age was 43 years (14-77); all pts had received all-trans retinoic acid (ATRA) and anthracyclines ± ara-C as first-line therapy. No patients received ATO as part of front-line therapy. According to Sanz Score, 26% were low risk, 45% intermediate and 29% high risk. 39% of pts had the bcr1/2 and 61% the bcr3 isoform of PML-RARA. Median duration of first remission was 493 days (93d to 5.7 years). The usual dosage of ATO was 0,15mg/kg/day, or regimens with the same cumulative dose were used. ATO induction therapy was combined with ATRA (45 mg/m2/day) in 40% of pts and during the consolidation cycle in 50% of pts, respectively. The median duration of ATO (± ATRA) for induction was 30 days and for consolidation 25 days. CNS relapses were treated with intrathecal application of methotrexate ± ara-C ± hydrocortisone and ATO. Among the 69 pts with first relapse, there were (Group A) 25 molecular and (Group B) 42 hematological relapses (bone marrow), in three pts combined with CNS involvement. Two pts had isolated CNS or extramedullary relapse. Main characteristics of pts at start of induction therapy in Group A vs. B were: median WBC count (x109/L) 4.4 (1.9-6.2) vs. 2.3 (0.5-102) (p=0.015); median platelet count (x109/L) 178 (40-392) vs. 87 (9-273) (p=0.0007); median Hb (g/L) 14 (10.6-15.7) vs. 12 (7.6-14.8) (p=0.0008). In Group A, none of the pts had coagulopathy compared to 8 of 25 (32%) pts with coagulopathy in Group B (p=0.004). In Group A, ATO therapy was not complicated by hyperleukocytosis and no episodes of differentiation syndrome were observed. In Group B, 9 (21%) pts had suspected or manifest differentiation syndrome (p=0.02), and additional chemotherapy was administered in 14 (33%) pts to control hyperleukocytosis. Other toxicities were rare and had no significant influence on therapy. In Group A, the rate of 2nd molecular remission after induction was 52% (13 of 25 pts) and after consolidation therapy 64%. No pt died. In Group B, 39 (88%) pts achieved 2nd CR, 2 (5%) pts were resistant and 3 (7%) pts died early from cerebral bleeding. Second molecular remission was reached in 12 of 32 (38%) pts after induction and in 62% after consolidation. Information on postconsolidation therapy was available in 45 pts of Group A and B. Of these, 14 pts underwent allogeneic, 18 pts autologous transplantation and 13 pts further therapy with ATO ± gemtuzumab ozogamicin. 11 of the 45 (24%) pts relapsed (median 2nd remission duration 10 months, 4 to 26), and 9 deaths were reported between 9 and 14 months after the end of consolidation therapy. In pts with 2nd and later relapse, despite previous exposure to ATO, further responses with this agent were observed. Conclusions: ATO is an effective therapy for all stages of relapsed APL. The results argue in favor of serial PML-RARA monitoring in front-line therapy of APL to allow early treatment of emergent relapses, avoiding hyperleukocytosis and risk of death due to bleeding and differentiation syndrome. Furthermore, the favorable toxicity profile of ATO seems to benefit the feasibility of subsequent transplantation. Disclosures: Lengfelder: Cephalon: Research Funding. Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.