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Yang, Kaixuan, Jian Wang, Jianli Miao, Jian Zhang, and Fujun Zhang. "All-polymer photodetectors with photomultiplication." Journal of Materials Chemistry C 7, no. 31 (2019): 9633–40. http://dx.doi.org/10.1039/c9tc02751c.
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Photomultiplication type all-polymer photodetectors were fabricated with P3HT : PZ1 (100 : 4, wt/wt) as active layers. The EQE values are 46 700% and 31 700% at 375 nm and 615 nm under a −20 V bias, respectively.
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WIESE, KURT L., and E. ROGER JACKSON. "Changes in Calculated Process Times and Drained Weight based on Soaking and Blanching of Kidney and Navy Beans." Journal of Food Protection 56, no. 3 (March 1, 1993): 239–42. http://dx.doi.org/10.4315/0362-028x-56.3.239.
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Kidney and navy beans were given different soaking/blanching treatments and canned in 300 × 407 and 603 × 700 cans with each container receiving equal amounts of dry weight of that bean. The process time (Bb) for kidney beans decreased as the amount of moisture in the beans increased. For both kidney and navy beans soaked for 2 h, the process time decreased when the fill weight was increased by 12 and 8%, respectively. For 0 and 2 h soaked kidney beans, the drained weights after processing were statistically the same even though the kidney beans soaked for 2 h had a moisture level 3.3-fold greater. Comparing 2 h soaked beans with fully soaked, blanched beans, the process time increased significantly for fully soaked, blanched beans by 9 and 46% for beans in 300 × 407 can and 603 × 700 can, respectively. The operation of blanching tended to lower the process time and drained weight of navy beans.
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Waller, Sophie E., Jeffrey Blackie, and Himanshu Goel. "053 GLUT-1 deficiency presenting as dopa-responsive dystonia: an atypical phenotype of a rare disease." Journal of Neurology, Neurosurgery & Psychiatry 90, e7 (July 2019): A17.2—A17. http://dx.doi.org/10.1136/jnnp-2019-anzan.46.
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IntroductionThe SLC2A1 gene encodes the glucose transporter GLUT1, responsible for normal glucose transport across the blood-brain barrier. Mutations in this gene have classically been associated with an epileptic encephalopathy referred to as GLUT-1 Deficiency Syndrome, which typically presents with early-onset refractory epilepsy, developmental delay and complex movement disorders.1 2 More recently, SLC2A1 variants have been identified in patients with paroxysmal exercise-induced dyskinesia (PED), with or without a history of epilepsy.3 4 Response to medication is typically poor; however, both seizures and dyskinesia may improve following implementation of a ketogenic diet.5 A single case of levodopa responsiveness has previously been described in a subject with SLC2A1 mutation and PED.5Methods and resultsWe describe a 47-year-old female with mild intellectual disability since childhood but no history of epilepsy, who developed episodic dystonia affecting the lower limbs in her early 20’s. A clinical diagnosis of dopa-responsive dystonia was made following a marked, sustained response to levodopa. There was no significant family history. In her 40’s she developed breakthrough dystonia with exertion and choreiform movements affecting the fingers and face. A subsequent dystonia panel identified a heterozygous variant c.[1199G>T];[=] (p.Arg400Leu) in the SLC2A1 gene. Cerebrospinal fluid glucose concentration was low (2.0 mmol/L). She declined a trial of a ketogenic diet.SLC2A1 variants are associated with PED; however, response to levodopa has not been widely reported.ConclusionIt is becoming increasingly evident that the phenotypic presentations of GLUT1 deficiency are diverse, and SLC2A1 testing should be considered in a broader range of patients.ReferencesWang, D, Kranz-Eble P, De Vivo DK. Mutational analysis of GLUT1 (SLC2A1) in Glut-1 Deficiency Syndrome. Human Mutation 2001;16:224–231.Klepper J, Leiendecker B. GLUT1 deficiency syndrome – 2007 update. Developmental Medicine & Child Neurology 2007;49:707–716.Schneider SA, Paisan-Ruiz C, Garcia-Gorostiaga I, Quinn NP, Weber YG, et al. GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias. Mov Disord 2009;24(11):1684–1696.Suls A, Dedeken P, Goffin K, Van Esch H, Dupont P. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, endoding the glucose transporter GLUT1. Brain 2008;131:1831–1844.Baschieri F, Batla A, Erro R, Ganos C, Cordivari C, Bhatia KP. Paroxysmal exercise-induced dystonia due to GLUT-1 mutation can be responsive to levodopa: a case report. J Neurol 2014;261:615–616.
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Listyasari, Nurin Aisyiyah, Ardy Santosa, Achmad Zulfa Juniarto, and Sultana MH Faradz. "Multidisciplinary Management of Disorders of Sex Development in Indonesia, A Prototype in Developing Country." Journal of Biomedicine and Translational Research 3, no. 1 (June 23, 2017): 17. http://dx.doi.org/10.14710/jbtr.v3i1.1209.
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Background : Disorder of sex development (DSD) patients require comprehensive management to improve quality of life. A standardized management protocol for patients in Indonesia is not yet available resulting in patients infrequently received a proper diagnosis. This study reported a multidisciplinary management DSD in Indonesia based on minimal diagnostic facilities and expertise in developing country.Objectives : The purpose of the study is to review the management of DSD patients in Indonesia relates to providing appropriate gender assignment and to improving patients quality of life.Methodology : We analyzed the records of DSD patient admitted to the division of Human Genetics Center for Biomedical Research (CEBIOR) Faculty of Medicine Diponegoro University, Semarang, Indonesia from May 2004 - December 2015. Data were collected and analyzed for physical examination, family pedigree karyotyping, hormonal assays and psychosocial. Other examination such as ultrasonography, Xray and Cytoscopy were also recorded for selected cases. Bimonthly, Sexual Adjustment Team (SAT) meeting was recorded.Results : From the total 617 DSD cases we found 426 cases (69,04 %) with 46, XY DSD, 117 cases (18,96%) with 46,XX DSD and 74 cases (12%) with sex chromosome DSD. Most of the patients in the group of 46, XY DSD are Unknown Male Undervirilization (UMU) with 256 cases (60.09%). As the majority cases of 46, XX DSD was Congenital Adrenal Hyperplasia with 81 cases (69.23%). The remaining cases were Androgen Action Disorder (AAD) with 140 cases (32.86%), 46, XY DSD Gonadal Dysgenesis with 30 cases (7.04%), Androgen Excess Disorders with 3 cases (2.56%), Defect of Mullerian Development with 19 cases (16,24%), 3 cases (2.56%) of Androgen Excess and 3 cases (2.56%) of 46, XX Gonadal Dysgenesis.Conclusion : Comprehensive management for DSD Patients help patient in diagnosis, gender assignment and support patient to improve quality of life. This multidisciplinary of DSD team is the only team in Indonesia that can be used as a model for other center in Indonesia as well as other developing countries with minimal diagnostic facilities.
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Híjar, Martha, Ricardo Pérez-Núñez, Elisa Hidalgo-Solórzano, Bernardo Hernández Prado, Rosario Valdez-Santiago, Erin B. Hamilton, Spencer L. James, et al. "Unintentional injuries in Mexico, 1990–2017: findings from the Global Burden of Disease Study 2017." Injury Prevention 26, Supp 1 (April 1, 2020): i154—i161. http://dx.doi.org/10.1136/injuryprev-2019-043532.
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BackgroundTo date, the burden of injury in Mexico has not been comprehensively assessed using recent advances in population health research, including those in the Global Burden of Disease Study 2017 (GBD 2017).MethodsWe used GBD 2017 for burden of unintentional injury estimates, including transport injuries, for Mexico and each state in Mexico from 1990 to 2017. We examined subnational variation, age patterns, sex differences and time trends for all injury burden metrics.ResultsUnintentional injury deaths in Mexico decreased from 45 363 deaths (44 662 to 46 038) in 1990 to 42 702 (41 439 to 43 745) in 2017, while age-standardised mortality rates decreased from 65.2 (64.4 to 66.1) in 1990 to 35.1 (34.1 to 36.0) per 100 000 in 2017. In terms of non-fatal outcomes, there were 3 120 211 (2 879 993 to 3 377 945) new injury cases in 1990, which increased to 5 234 214 (4 812 615 to 5 701 669) new cases of injury in 2017. We estimated 2 761 957 (2 676 267 to 2 859 777) disability-adjusted life years (DALYs) due to injuries in Mexico in 1990 compared with 2 376 952 (2 224 588 to 2 551 004) DALYs in 2017. We found subnational variation in health loss across Mexico’s states, including concentrated burden in Tabasco, Chihuahua and Zacatecas.ConclusionsIn Mexico, from 1990 to 2017, mortality due to unintentional injuries has decreased, while non-fatal incident cases have increased. However, unintentional injuries continue to cause considerable mortality and morbidity, with patterns that vary by state, age, sex and year. Future research should focus on targeted interventions to decrease injury burden in high-risk populations.
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Doré, M., S. I. Simon, B. J. Hughes, M. L. Entman, and C. W. Smith. "P-selectin- and CD18-mediated Recruitment of Canine Neutrophils under Conditions of Shear Stress." Veterinary Pathology 32, no. 3 (May 1995): 258–68. http://dx.doi.org/10.1177/030098589503200307.
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Neutrophil mobilization at sites of inflammation or thrombosis involves the participation of several adhesion molecules expressed on neutrophils and vascular endothelial cells. Local vascular damage with disruption of the endothelium results in adhesion of platelets to the exposed subendothelium, and these platelets could also participate in neutrophil recruitment. This initial phase of mobilization could be followed by heterotypic aggregation to recruit more leukocytes in the area. The present study first examined the interactions of adherent canine platelets and flowing canine neutrophils using an in vitro system that simulates vascular flow conditions. Results showed that collagen-adherent platelets express the adhesion molecule P-selectin on their surface and can support neutrophil arrest (612 ± 43 neutrophils/mm2) at shear stresses of approximately 2.5 dynes/cm2. Both transient adhesion (manifested by a rolling-type behavior) and complete arrest were observed. These interactions could be totally inhibited by a monoclonal antibody directed against platelet P-selectin (24 ± 18 neutrophils/mm2) but not by a monoclonal antibody against neutrophil CD18 (625 ± 46 neutrophils/mm2). Additionally, under shear mixing conditions (700 RPM), canine blood leukocytes exhibited aggregation (>80% singlets recruited into aggregates after 5 minutes), and this process does not involve P-selectin but is dependent on the neutrophil integrin CD 18. However, stimulation of the blood with platelet-activating factor (5-20 ng/ml) induced a rapid aggregation with a significantly greater number of aggregates when compared with stirring alone (68.3% ± 3.2% versus 35.2% ± 6.3% at 1 minute, P < 0.05), and this aggregation was both P-selectin and CD 18 dependent. Overall, these two mechanisms of leukocyte recruitment (neutrophil arrest on adherent platelets and aggregation) could act sequentially and in a cooperative manner to bring into close contact platelets and neutrophils at sites of inflammation and thrombosis in pathologic conditions in the dog.
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Bracarda, Sergio, Roberto Iacovelli, Mimma Rizzo, Marta Rossi, Luca Galli, Giuseppe Procopio, Flavia Longo, et al. "Retrospective observational study of sunitinib administered on schedule 2/1 in patients with metastatic renal cell carcinoma (mRCC): The rainbow study." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 471. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.471.
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471 Background: Sunitinib is a standard of care in first line mRCC; however, an increasing percentage of treatment-related adverse events are observed in the last 2 treatment weeks of the standard schedule 4/2 (4-weeks-on/2-weeks-off). In a multicenter, retrospective study, we evaluated the efficacy and safety of a modified 2/1 schedule (2-weeks-on/1-week-off), largely used in Italy based on a favorable initial experience. Methods: Data from all consecutive patients (pts) treated in 24 Italian centers with sunitinib on schedule 2/1 were analyzed according to the following groups: Group A, pts moved to schedule 2/1 because of treatment-related toxicities during initial therapy using schedule 4/2; Group B, pts treated ab initio with schedule 2/1, mainly because of poorer clinical conditions. A small group of pts treated with schedule 4/2 served as a control (Group C). Results: 276 consecutive pts treated from November 2005 to August 2013 were analyzed, including 249 treated with schedule 2/1 (Group A, n=208; Group B, n=41; respectively, median age 62 and 61 years; clear cell 94.7% and 87.8%; MSKCC good/intermediate/poor 47.1%/46.6%/6.3% and 36.5%/53.7%/9.8%; brain metastases 3.8% and 9.8%) and 27 pts in Group C (median age 59 years; clear cell 96.3%; MSKCC good/intermediate/poor 22.2%/70.4%/7.4%; no brain metastases). In Group A, the median treatment duration (TD) was 28.2 months (m) (with a median of 4.3 on the initial schedule 4/2 and 19.7 on the following schedule 2/1); median progression-free survival (PFS) was 38.6 m (95% CI, 24.0-58.6). In Group B (with less clear cell cases and more pts of intermediate risk or with brain metastases) median TD was 7.8 m and median PFS was 9.6 m (95% CI, 6.3-14.2). Median TD in Group C was 10.4 m. Maximum toxicity grade (≥3) and specific toxicities such as fatigue and hypertension were significantly reduced on schedule 2/1 in Group A compared with the initial schedule 4/2 (respectively, 8% vs 46% and 0% vs 10%, p < .001, and 2% vs 9%, p = .007). Conclusions: In our experience, sunitinib on a modified schedule 2/1 has an improved safety profile and increased efficacy compared with schedule 4/2. Prospective evaluation of this schedule is warranted.
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Ma, Weijing, Christian Opp, and Dewei Yang. "Past, Present, and Future of Virtual Water and Water Footprint." Water 12, no. 11 (November 2, 2020): 3068. http://dx.doi.org/10.3390/w12113068.
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Virtual water and water footprint have received increasing attention. However, no published research has conducted a quantitative and objective review of this field from the perspective of bibliometrics. Therefore, based on the Web of Science Core Collection, this study employs CiteSpace to quantitatively analyze and visualize information about countries, institutions, and authors that have conducted virtual water and water footprint research over the past two decades. As of July 2020, there were 1592 publications on virtual water and water footprint, showing an increasing trend overall. The annual average number of publications was only 7.4 in 1998–2008, while it was 126.5 in 2009–2019. Among them, up to 618 publications in the field of environmental science, accounting for 46%. China was the most productive country with a total of 344 articles, but the Netherlands had the strongest influence with a betweenness centrality of 0.33, indicating its leading position. It is essential to strengthen cooperation between developed (water-rich) and developing (water-poor) countries and to incorporate virtual water into social water cycle research. This study is expected to provide a new perspective for investigating the research frontiers and hot spots of virtual water and water footprint research.
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Victoir, K., J. C. Dujardin, S. De Doncker, D. C. Barker, J. Arevalo, R. Hamers, and D. Le Ray. "Plasticity of gp63 gene organization in Leishmania (Viannia) braziliensis and Leishmania (Viannia) peruviana." Parasitology 111, no. 3 (September 1995): 265–73. http://dx.doi.org/10.1017/s0031182000081828.
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SUMMARYThe genomic organization of gp63 genes in 4 and 7 isolates of Leishmania braziliensis and L. peruviana, respectively was studied by RFLP analysis with 3 restriction enzymes (Bgl I, Sal I and Apa I). Our results showed a marked polymorphism among isolates. Some characters were specific to L. braziliensis or to L. peruviana, and others specific to the respective biogeographical populations of L. peruviana. The average minimum copy number of gp63 genes was found to be higher in L. braziliensis (71) than in L. peruviana (46), suggesting that deletion of gp63 genes might be partially involved in the size decrease of the chromosome bearing gp63 genes, observed between those 2 species (from 700 to 610 kb). Our results may suggest the existence of at least 2 arrays of heterologous gp63 repeats, varying in relative copy number between L. braziliensis and L. peruviana, and among isolates of the latter species. Rearrangement of the gp63 genes was observed during long-term in vitro maintenance of a reference strain of L. braziliensis. These observations document the existence of a dynamic gp63 gene organization in Leishmania of the braziliensis complex.
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Smith, Katie, L. Lanningham-Foster, Amy Welch, and Christina Campbell. "Web-Based Behavioral Intervention Increases Maternal Exercise but Does Not Prevent Excessive Gestational Weight Gain in Previously Sedentary Women." Journal of Physical Activity and Health 13, no. 6 (June 2016): 587–93. http://dx.doi.org/10.1123/jpah.2015-0219.
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Background:Innovative methods are warranted to optimize prenatal outcomes. This study’s objective was to determine if a web-based behavioral intervention (BI) can prevent excessive gestational weight gain (GWG) by increasing physical activity (PA).Methods:Participants were randomized to usual care (UC; n = 21) or BI (n = 24) between 10 to 14 weeks gestation. GWG, PA, and diet were assessed at baseline, mid-, and late pregnancy.Results:No differences in GWG or adherence to GWG recommendations presented between groups. Total UC MET-minutes significantly decreased from baseline to late-pregnancy (1,234 ± 372 MET-minutes, P = .013). Mid-pregnancy sustained PA was greater for BI than UC (20-minute PA bouts: 122 ± 106 vs. 46 ± 48 minutes/week, P = .005; 30-minute PA bouts: 74 ± 70 vs. 14 ± 24 minutes/week, P < .001), and greater for BI at mid-pregnancy compared with baseline (20-minute PA bouts: 61.3 ± 21.9; 30-minute PA bouts: 39.6 ± 14.8, both P < .05). BI energy intake at mid-pregnancy significantly increased from baseline (336 ± 127 kcals, P = .04) and was significantly greater than UC (2,503 ± 703 vs. 1,894 ± 594, P = .005).Conclusions:Sedentary pregnant women should increase PA but may need additional dietary counseling to prevent excessive GWG.
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BOUGIOUKLIS (Π. ΜΠΟΥΠΟΥΚΛΗΣ), P., I. GEORGOPOULOU (Ι. ΓΕΩΡΓΟΠΟΥΛΟΥ), and P. IORDANIDIS (Π. ΙΟΡΔΑΝΙΔΗΣ). "Determination of breakthrough maternal antibodies titres by two intermediate and two intermediate plus vaccine strains against Gumboro disease, in commercial broilers." Journal of the Hellenic Veterinary Medical Society 55, no. 3 (December 6, 2017): 217. http://dx.doi.org/10.12681/jhvms.15097.
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Two field trials (termed A and B) were carried out on 4 farms (groups) with 20,000 broilers each. The groups in A and Β were named Al, A2, A3, A4 and Bl, B2, B3, B4, respectively. The chicks in A were hatched from breeders of 39, 43, 46, and 56 weeks-old and in Β from 27, 31, 52, and 54 weeks-old. One vaccination to each group was administered against Gumboro in drinking water, in each trial. Intermediate plus vaccines I and II were used in groups 1 and 2 and intermediate I and II in groups 3 and 4. In A the vaccinations were conducted when the chicks were 15-days-old and in Β at 19-days-old. In both trials blood samples were collected at 8, 15, 19, 23, 30 and 37 days of age. Serum examinations by ELISA established that in groups Al, A2, A3 and A4 vaccinations were carried out in the presence of mean maternal antibody titres 7.1 log2, 7.2 log2, 6.3 log2 and 6.4 log2, respectively. A regression of antibodies up to 37 days were observed in these 4 groups. In groups Bl, B2, B3 and B4 the vaccinations were carrie out in the presence of mean maternal antibody titres 7.3 log2, 7.4 log2,3.2 log2 and 3.3 log2, respectively. A strong serological response from 30 days was observed in these 4 groups. It is remarkable that intermediate plus vaccines to 7.3log2 and 7.41og2 mean maternal antibody titres caused active immune response in groups Bl and B2, respectively, contrary to what happened to similar titres in groups Al and A2. This important observation showed that age may be one of the main factors that influences the effectiveness of vaccinations, as well as the interference of maternal antibodies and the virulence of vaccines strains. The results of both field trials indicate that both intermediate vaccines at 15-days-old did not breakthrough mean maternal antibody titres higher than 6.3 log2, whereas intermediate plus vaccines succeded to breakthrough mean maternal antibody titres lower than 7.4 log2 at 19-days-old.
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Rosettie, Katherine L., Jonah N. Joffe, Gianna W. Sparks, Aleksandr Aravkin, Shirley Chen, Kelly Compton, Samuel B. Ewald, et al. "Cost-effectiveness of HPV vaccination in 195 countries: A meta-regression analysis." PLOS ONE 16, no. 12 (December 20, 2021): e0260808. http://dx.doi.org/10.1371/journal.pone.0260808.
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Cost-effectiveness analysis (CEA) is a well-known, but resource intensive, method for comparing the costs and health outcomes of health interventions. To build on available evidence, researchers are developing methods to transfer CEA across settings; previous methods do not use all available results nor quantify differences across settings. We conducted a meta-regression analysis of published CEAs of human papillomavirus (HPV) vaccination to quantify the effects of factors at the country, intervention, and method-level, and predict incremental cost-effectiveness ratios (ICERs) for HPV vaccination in 195 countries. We used 613 ICERs reported in 75 studies from the Tufts University’s Cost-Effectiveness Analysis (CEA) Registry and the Global Health CEA Registry, and extracted an additional 1,215 one-way sensitivity analyses. A five-stage, mixed-effects meta-regression framework was used to predict country-specific ICERs. The probability that HPV vaccination is cost-saving in each country was predicted using a logistic regression model. Covariates for both models included methods and intervention characteristics, and each country’s cervical cancer burden and gross domestic product per capita. ICERs are positively related to vaccine cost, and negatively related to cervical cancer burden. The mean predicted ICER for HPV vaccination is 2017 US$4,217 per DALY averted (95% uncertainty interval (UI): US$773–13,448) globally, and below US$800 per DALY averted in 64 countries. Predicted ICERs are lowest in Sub-Saharan Africa and South Asia, with a population-weighted mean ICER across 46 countries of US$706 per DALY averted (95% UI: $130–2,245), and across five countries of US$489 per DALY averted (95% UI: $90–1,557), respectively. Meta-regression analyses can be conducted on CEA, where one-way sensitivity analyses are used to quantify the effects of factors at the intervention and method-level. Building on all published results, our predictions support introducing and expanding HPV vaccination, especially in countries that are eligible for subsidized vaccines from GAVI, the Vaccine Alliance, and Pan American Health Organization.
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Baladi, Zameer Hussain. "A PATTERN OF RESEARCH IN CORONAVIRUSES IN SAUDI ARABIA FROM 2014 – 2018." EUREKA: Social and Humanities 4 (July 31, 2020): 41–46. http://dx.doi.org/10.21303/2504-5571.2020.001334.
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The aim: to observe the contribution of authors and the collaboration of institutes functioning in Saudi Arabia through the bibliometric review of literature in Coronaviruses. Design/Methods/Approach: Authors as solo or corroborators in research are the main sources to retrieve the material of their original articles, case reports and review articles published from 2014–2018 in PubMed indexed journals for estimation and tabulation. Results: Total 895; 3.5 % institutes (522; 58.3 % functioning locally and 373; 41.6 % internationally) in Saudi Arabia with the support of 1878; 7.4 % authors produced 253 articles from 2014 to 2018. Position of the author always matters in research, 207; 81.8 % authors had the first position followed by 28; 11 % as a second. Majority 72; 28.4 % articles published by single institute followed 46; 18.1 % and 49; 19.3 % by two and three institutes. Johns Hopkins Aramco Healthcare, Dhahran, Kingdom of Saudi Arabia publish 57; 6.3 % stand on lead followed by the Ministry of Health (All Regions) Kingdome of Saudi Arabia and King Saud bin Abdulaziz University for Health Sciences, Jeddah & Riyadh, Saudi Arabia. Pathology and Laboratory Medicine, Community & General Medicine and Hospital Administration & Health Informatics were major disciplines of publications. Three journals, Journal of Infectious and Public Health, International Journal of Infectious Diseases and American Journal of Infection Control grab 147; 58.1 % share of publishing research. Conclusion: This study illustrates the determinations of the Saudi public and private healthcare sectors to handle the epidemic situation and uphold the esteem of people residing in catchment areas by means of technical, logistical and financial aid to managers and decision-makers.
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Ullauri González, Carmen Alejandra, and Liena Shinkarenko. "Susceptibilidad antimicrobiana de bacterias patógenas aisladas en urocultivos, Hospital General "Isidro Ayora" Loja." Investigación, Tecnología e Innovación 8, EE (November 30, 2016): 123–30. http://dx.doi.org/10.53591/iti.v8iee.146.
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Las infecciones de vías urinarias constituyen una de las consultas más comunes en atención primaria. Los agentes etiológicos frecuentemente desarrollan resistencia bacteriana que complica el tratamiento. Se realizó esta investigación en un Hospital de 2º nivel de la Ciudad de Loja, Ecuador, en muestras de pacientes atendidos en esa casa asistencial y que obtuvieron una orden médica para examen de urocultivo. Se recibieron 619 muestras. De ellas 237 (38,28%) resultaron ser positivas. Para la identificación bacteriana se usaron técnicas de Bacteriología convencional como el cultivo, conteo de bacterias y pruebas bioquímicas. Para el antibiograma se usó la técnica de difusión en disco de Kirby Bauer. En el tamizaje y confirmación de producción de BLEE se usó procedimiento recomendado y establecido por el CLSI. Se identificaron, como principales agentes etiológicos bacterias pertenecientes a la familia Enterobacteriaceae, con la especie más frecuente E. coli. Los bacilos Gram negativos presentaron niveles de sensibilidad sobre el 70% frente a cefalosporinas de tercera y cuarta generación, ciprofloxacina, aztreonam, ampicilina sulbactam y nitrofurantoína y menores a 50% para ácido nalidíxico. Los patógenos Gram positivos aislados en urocultivos mostraron perfil de sensibilidad disminuida para penicilina en el caso de Staphylococcus sp. 60% y para Enterococcus sp. 10%. Se detectó producción de BLEE del 15,52% en cepas de Enterobacteriaceae recuperadas, con frecuencia más alta en K. pneumoniae. El mayor número de cepas productoras de BLEE fue recuperado de muestras de pacientes de sexo femenino y consulta externa, con un 74% y 70,4%, respectivamente, y de pacientes mayores de 46 años 33,34%.
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Anuriev, A. M., V. I. Gorbachev, T. M. Anurieva, and I. L. Petrova. "The using of a neurally adjusted ventilatory assist in premature infants. Article." Alexander Saltanov Intensive Care Herald, no. 2 (June 15, 2020): 122–28. http://dx.doi.org/10.21320/1818-474x-2020-2-122-128.
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Introduction. The problem of choosing an adequate mode and parameters of mechanical ventilation (MV) in premature infants remains extremely important in neonatology. Objectives. To assess the effect of nerve-regulated MV on the gas composition of the blood, the concentration of malondialdehyde (MDA) and glutathione in premature infants. Materials and methods. The study included 46 premature infants who underwent MV from birth. The gestational age of children was 25-32 weeks, birth weight - 520-1100 grams. Two study groups were formed. The first group consisted of newborns with respiratory support in the Synchronized Intermittent Mandatory Ventilation (SIMV), the second group consisted of children who underwent Neurally Adjusted Ventilatory Assist (NAVA).At birth and during the first three days, the parameters of the gas composition of venous blood are measured: pH, pCO2, pO2, BE; lactate level. Concentrations of MDA and glutathione determine the first and seventh days of life. Results. In children of the first group, hypocapnia was observed during the first three days of life, while the minimum level of partial pressure of carbon dioxide (pCO2) was observed on the first day and amounted to 32.0 (24.9; 37.8) mm Hg. In patients of the second group, pCO2 indices were close to the reference ones and amounted to 36.0 (32.5; 42.2) mm Hg (p = 0.01).Indicators of excess base (BE) were reduced in patients in both groups and on the third day amounted to -6.4 (-7.4;-5.2) mmol/l in children of the first group and -4.7 (-6.0;-3.1) mmol/l in children of the second group (p = 0.02). No statistically significant differences in the partial pressure of oxygen (pO2), lactate, and glutathione were observed. Values of MDA were increased in patients of the first and second groups, however, a decrease in its concentration was observed in the dynamics in both groups. On the 7th day, in patients of the first group, the concentration of malondialdehyde decreased from 13.4 nmol/l to 12.0 nmol/l. In patients of the second group, its indices decreased twofold from the initial ones and amounted to 6.3 (5.4; 7.4) nmol/l (p = 0.01). Conclusion.The use of NAVA ventilation in premature infants ensures a constant gas composition of the blood, and also prevents the activation of lipid peroxidation resulting from hypoxia.
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Khan, Mehran, Ashfaq Ahmed, Fraz Umer, Atiq uz Zaman, Saeed Ahmad, Naeem Ahmed, Shahzad Javed, and Amer Aziz. "TOTAL KNEE ARTHROPLASTY?;." Professional Medical Journal 24, no. 07 (July 3, 2017): 992–96. http://dx.doi.org/10.29309/tpmj/2017.24.07.1084.
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The treatment of choice for osteoarthritic knee is Total knee arthroplasty (TKA)and the most important problem in it is the blood loss. Objectives: To compare the postoperativemean blood loss with Tranexamic acid versus control after Total Knee Arthroplasty.Study Design: Randomized controlled trial. Setting: Ghurki Trust Teaching Hospital Lahore.Period: 01 year. Methodology: 100 patients were included and divided in 2 groups, selectedby non-probability purposive sampling, fulfilling inclusion and exclusion criteria. Group T(Tranexamic) received 15mg/kg IV Tranexamic acid 10 minutes before inflating tourniquet andthe same dose intravenously 3 hours post-operatively. Group C (control) received placebo(normal saline) intravenously. Blood loss collected in a container was measured with syringe/jarafter 24 hours of surgery. Results: In group C there were 23(46%) males and 27(54%) femaleswith male to female ratio 1:1.7 with mean age of 64yrs ± 6.3 yrs. In group T there were 28(56%)males and 22 (44%) females with male to female ratio 1.2:1 with mean age of 65yrs ± 7.4 yrs.After 24 hours Mean blood loss in Group C were 694 ±151 ml with 74 % patient in range of600-900ml while Mean blood loss in Group T were 388 ml ±105 ml with 76 % patient in rangeof 300-600ml. Mean decrease in blood loss with the use of tranexamic acid { mean blood lossin T group – mean blood loss in T group } were 306 ml which were statistically significant(p<0.05) using t Test. Conclusion: Tranexamic acid is a potent anti-fibrinolytic agent and its use intotal knee arthroplasty results in decrease in post-operative blood loss thereby decreasing theneed of blood transfusion.
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Tufa, Tafese B., Fuchs André, Sileshi Abdissa, Zewdu Hurissa, Hans Martin Orth, Kaasch Achim, Mackenzie Colin, Pfeffer Klaus, Feldt Torsten, and Häussinger Dieter. "619. High Multidrug-Resistant due to TEM and CTX-M-1 Types of Extended-Spectrum β-Lactamase and blaNDM-1 Type Carbapenemase Genes among Clinical Isolates of Gram-Negative Bacilli in Asella, Central Ethiopia." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S288. http://dx.doi.org/10.1093/ofid/ofz360.687.
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Abstract Background Acute infectious diseases and sepsis are among the leading causes of mortality in Ethiopia. The lack of local data concerning causative pathogens and resistance patterns results in suboptimal empirical treatment and unfavorable clinical outcome. The objective of this study was the characterization of bacterial pathogens in hospitalized patients with febrile infections in Central Ethiopia. Methods In total, 684 patients ≥1 year of age with fever admitted to the Asella Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were cultured. Susceptibility testing was performed using the Kirby–Bauer method and VITEK2. Confirmation of species identification and identification of resistance genes were conducted using MALDI-ToF and PCR at a microbiology laboratory in Düsseldorf, Germany. Results In total, 684 study participants were included; 54% were male and mean age was 26.7 years. Thus, the overall culture positivity rate was 7.5%. Of the 83 cultured organisms, 38(46%) were Gram-negative, 43(52%) Gram-positive, and 2(2%) Candida species. Among the 38 Gram-negative isolates, 16(42%) were E. coli, 15(39%) K. pneumoniae, and 4(11%) P. aeruginosa. Resistance against commonly used antibiotics for Gram-negative at the study site was: piperacillin/tazobactam 48%(13), ampicillin/sulbactam 93% (25), cefotaxime 89%(24), ceftazidime 74%(20), Cefipime 74%(20), meropenem 7%(2), amikacin 4% (1) and gentamicin 56%(15). Of 27 Gram-negative available for resistance-gene detection, blaNDM-1 was detected in one K. pneumoniae isolate and blaNDM-1 plus blaOXA-51 in A. baumannii. 81%(22/27) of the Gram-negative rods were confirmed to contain ESBL-genes as follows: TEM 17(77%), CTX-M-1-group 15(68%), SHV-6(27%) and CTX-M-9-group 2(9%). Among isolated S.aureus, 1(5%) was confirmed to be Methicillin-resistant S. aureus. Conclusion We found a high prevalence (81%) of ESBL-producing bacteria and 7.4% carbapenem resistance at the study site. More than half of Gram-negative isolates had two or more mobile resistance genes. These findings warrant the need for local national multidrug-resistant surveillance. Strengthening of antimicrobial stewardship programs is needed in order to face the threat of multidrug-resistant bacteria. Disclosures All authors: No reported disclosures.
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Wahlers, Thorsten C. W., Martin Andreas, Parwis Rahmanian, Pascal Candolfi, Barbora Zemanova, Christophe Giot, Enrico Ferrari, and Günther Laufer. "Outcomes of a Rapid Deployment Aortic Valve versus its Conventional Counterpart." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 13, no. 3 (May 2018): 177–83. http://dx.doi.org/10.1097/imi.0000000000000509.
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Objective The aim of this study was to compare outcomes after rapid-deployment aortic valve replacement (RDAVR) and conventional aortic valve replacement (AVR) from two studies. Methods Patients who underwent RDAVR (INTUITY valve) in the prospective, 5-year, single-arm multicenter TRITON study, or conventional AVR (Perimount Magna Ease valve) in the prospective Perimount Magna Ease postmarket study, were propensity score matched and compared for procedural, hemodynamic, safety, and clinical outcomes. Results Matched RDAVR (n = 106) and conventional AVR (n = 106) patients had similar baseline characteristics (mean ± SD age, 72.8 ± 7.6 vs 72.5 ± 7.4 years; male 59.4% vs 61.3%) and procedures (concomitant procedures: 41.5% vs 50.9%). Mean ± SD aortic cross-clamp time was significantly shorter in RDAVR than AVR patients (51.8 ± 20.9 vs 73.9 ± 33.2 minutes; P < 0.001), as was mean cardiopulmonary bypass time (82.8 ± 34.2 vs 102.4 ± 41.7 minutes; P < 0.001). At 1 year, RDAVR patients showed significantly lower mean ± SD and peak aortic valve gradients (9.0 ± 3.4 and 17.0 ± 6.2 mm Hg, respectively) than conventional AVR patients (13.4 ± 5.5 and 24.2 ± 10.8 mm Hg, respectively; all P < 0.001). Patient-prosthesis mismatch was significantly less common with RDAVR than with AVR [overall: 16/66 (24.2%) vs 46/76 (60.5%); P = 0.007; severe: 2/66 (3.0%) vs 13/76 (17.1%)]. There were no significant differences between the RDAVR and AVR groups regarding 30-day safety endpoints. Survival rates in the RDAVR and conventional AVR groups were, respectively, 99.1% and 100.0% at 30 days, 97.1% and 95.1% at 1 year, and 93.3% and 94.1% at 3 years ( P = nonsignificant). Conclusions In this retrospective study with matched populations, the RDAVR with the INTUITY valve system provided superior procedural and hemodynamic outcomes than a standard bioprosthesis without compromising safety.
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Wang, Yucai, Umar Farooq, Brian K. Link, Melissa C. Larson, Rebecca L. King, Matthew J. Maurer, Cristine Allmer, et al. "Late Relapses in Patients With Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy." Journal of Clinical Oncology 37, no. 21 (July 20, 2019): 1819–27. http://dx.doi.org/10.1200/jco.19.00014.
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PURPOSE In patients with diffuse large B-cell lymphoma (DLBCL), most relapses occur within the first 2 years of diagnosis. We sought to define the rate and outcome of late relapses that occurred after achieving event-free survival at 24 months (EFS24). METHODS We prospectively followed 1,324 patients with newly diagnosed DLBCL from 2002 to 2015 and treated with immunochemotherapy. Cumulative incidences of late DLBCL and indolent lymphoma relapses were analyzed as competing events. Postrelapse survival was defined as time from first relapse to death from any cause. RESULTS In 847 patients who achieved EFS24, the cumulative incidence of late relapse was 6.9% at 3 years, 9.3% at 5 years, and 10.3% at 8 years after EFS24. The incidence of DLBCL relapse was similar in patients with DLBCL alone at diagnosis (6.3% at 5 years), compared with patients with concurrent indolent lymphoma at diagnosis (5.2%; P = .46). However, the rate of indolent lymphoma relapse was higher in patients with concurrent indolent lymphoma (7.4% v 2.1% at 5 years; P < .01). In patients with DLBCL alone, the rate of DLBCL relapse was similar in the germinal center B-cell–like (GCB) (4.1% at 5 years) and non-GCB (4.0%; P = .71) subtypes, whereas the rate of indolent lymphoma relapse was higher in patients with the GCB subtype (3.9% v 0.0% at 5 years; P = .02). Postrelapse survival was inferior for patients who relapsed with DLBCL than for those who relapsed with indolent lymphoma (median 29.9 months v unreached; P < .01). CONCLUSION Patients with DLBCL with a concurrent indolent lymphoma and those with the GCB subtype had a higher rate of late relapse, owing to increased relapses with indolent lymphoma. Patients who relapsed with DLBCL had a worse prognosis than those who relapsed with indolent lymphoma.
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McLean, Natasha, and Kathrine A. Handasyde. "Sexual maturity, factors affecting the breeding season and breeding in consecutive seasons in populations of overabundant Victorian koalas (Phascolarctos cinereus)." Australian Journal of Zoology 54, no. 6 (2006): 385. http://dx.doi.org/10.1071/zo06015.
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It is important to have knowledge of basic population parameters to understand how these vary geographically and temporally and how they contribute to population dynamics. This paper investigates three of these parameters in Victorian koala populations: sexual maturity, aspects of the breeding season, and the continuity of individuals’ breeding. The investigation was carried out in koalas of known-age in two free-living (Redbill Creek on French Island and Brisbane Ranges) and one semi-captive (the Koala Conservation Centre on Phillip Island) population as well as koalas of unknown age in four Victorian populations of overabundant koalas: Mt Eccles and Framlingham in south-west Victoria, French Island in Western Port and Snake Island in south Gippsland. At sexual maturity, female koalas had a mean age (±95% confidence interval) of 24.4 months (23.5–25.3 months), a mean head length of 125 mm (124–127 mm) and a mean body mass of 6.6 kg (6.3–6.8 kg). Only 7.4% of independent females (of unknown age) were carrying young when they weighed less than 6 kg. The breeding season was more restricted in the south-west populations. At Framlingham and Mt Eccles 85% and 91% of births, respectively, occurred between December and March. At Snake and French Islands only 46% and 53% of births, respectively, were recorded in the same period. In the Chlamydia-free population (Red Bill Creek) none of the koalas that were monitored stopped breeding and then resumed breeding in a subsequent season whereas many females from Chlamydia-infected populations (Brisbane Ranges and the Koala Conservation Centre) did so. This variation in reproductive patterns is likely to make an important contribution to the variation in the demography observed in different koala populations.
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Galvin, Robert, Danielle Maeser, Robert Gruener, and R. Stephanie Huang. "OTME-11. Characterizing the immunologic context of pediatric brain tumors." Neuro-Oncology Advances 3, Supplement_2 (July 1, 2021): ii15. http://dx.doi.org/10.1093/noajnl/vdab070.062.
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Abstract Therapy for pediatric central nervous system (CNS) malignancies can be toxic, and outcomes are suboptimal. Immunotherapy holds promise as a therapeutic avenue, but the poorly understood microenvironment limits its application. The Children’s Brain Tumor Network (CBTN) released the Pediatric Brain Tumor Atlas, containing expression profiles of nearly 700 primary CNS tumors. To study the immune microenvironment, a classification from The Cancer Genome Atlas project is applied. High-grade lesions are predominantly lymphocyte deplete (C4, 81%) or immunologically quiet (C5, 11%). Low-grade lesions are more mixed with 46% C4, 21% C5, and a higher proportion of inflammatory subtype (C3, 31%). For survival parameters, adjusting for tumor grade and extent of resection, the hazard ratio is 2.2 (0.78 – 6.3), p = 0.13) and 2.4 (0.6 – 10.0, p = 0.24) for C4 and C5, respectively. With no events among low-grade tumors, progression-free survival will be another useful metric and released by CBTN in April. Deconvolution of immune cell gene signatures among C4 samples reveals decreased abundance of T cells (OR 0.26, 0.1 – 0.5) yet increasing T-cell abundance is associated with decreased survival time in high-grade samples (HR 3.7, 1.4 – 10.1). Additionally, there are increased macrophage and decreased microglia signatures among high-grade samples and the C4 and C5 subtypes. It is hypothesized that expression of inhibitory immunomodulators contributes to a pro-tumorigenic microenvironment and represent potential therapeutic targets. In lieu of normal tissue in the data set, differential gene expression experiments between disease states reveals upregulated immunomodulators. Conventional immunomodulators, e.g. PDL1 and CTLA4, are expressed in low-grade samples with C3 subtype, which is abundant in craniopharyngioma. Alternative inhibitory immunomodulators, e.g. KDM1A, EZH2, CD276, are significantly expressed in high-grade samples including diffuse midline glioma. Overall, our analysis contributes to the understanding of the immune microenvironment and identifies potential mechanisms of immune escape among pediatric CNS tumors.
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Walker, Irwin R., Donald M. Arnold, and Jim A. Julian. "Survival of HIV Infected Individuals with Hemophilia after 20 Years: From the Canadian Hemophilia Registry." Blood 104, no. 11 (November 16, 2004): 3085. http://dx.doi.org/10.1182/blood.v104.11.3085.3085.
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Abstract Background : Patients with hemophilia A and B have been tracked by the Canadian Hemophilia Registry since 1980. The total number on the Registry is 3307 (A=2721, B=586) of which 662 were/are HIV-positive. New HIV and HCV infections ceased after 1985 and 1988 respectively with the introduction of safer blood products; HIV-infected individuals with hemophilia therefore resemble a cohort with HIV infection that was acquired in a relatively narrow time period about 20 years ago. Current status of HIV-positive patients is Active 250 (37.8%), Deceased 406 (61.3%), Lost to Follow Up 9 (0.9%). Follow up data is available for 3135/3307 (95% of all patients), and for 656/662 (99% of HIV-positive patients). We previously reported (Haemophilia1998;4:714) a peak in the death rate of HIV-positive individuals during the years 1991 to 1993 with a subsequent decline. Objective : To update the rate and causes of death among HIV positive hemophilia patients in Canada with current information. HIV-Related Mortality : The annual number of deaths in the HIV-positive group has been [year-#(deaths per 100 person-years)], 1980-0(0), 81-0(0),82-0(0),83-3(0.45),84-1(0.15),85-2(0.30),86-12(1.8),87-12(1.9),88-21(3.3),89-25(4.1),90-24(4.1),91-45(8.0),92-38(7.4),93-Currently, 256/662 (38.7%) are alive. Causes of Death (HIV+) : The commonest primary causes of death in HIV-positive individuals have been: [cause #(%)] AIDS 284(70), liver failure 45(11), bleeding 18(4.4) and infections 15(3.7). Twenty-eight patients had liver disease listed as a secondary or contributing cause of death; thus liver disease was the primary or contributory cause of death in 45+28=73 individuals (18% of HIV-positive deaths). HCV-Related Deaths : HCV status is positive in 1151 of the total population of 3307 (35%) individuals in the registry, negative in 1260 (38%) and unknown in 896 (27%). Of HIV-positive individuals, 448 (68%) are co-infected with HCV, 53 of whom have died with liver failure (12% overall, 18% of deaths). HIV/HCV co-infected individuals have higher overall mortality than those not co-infected (46% vs. 12%, p<0.0001). In addition, HCV singly-infected individuals have lower overall mortality (7%). 703 HIV-negative individuals are infected with HCV, of whom 7 have died with liver failure (1% overall, 13% of deaths). Conclusions : The death rate of HIV-positive individuals peaked in the years 1991-3 and decreased thereafter with 38% of individuals still living at 20 years follow up. However deaths still occur at an annual rate of 3–5%. HIV/HCV co-infected individuals have the highest mortality and HCV single-infected individuals have the lowest mortality of those with transfusion-transmitted infection. Liver failure is a common mode of death in both HIV- and HCV-infected individuals.
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Gomes, Marília de Brito, Gildásio R. da Silva Júnior, and Eliete Leão da S. Clemente. "Variabilidade da pressão arterial de consultório em pacientes com diabetes mellitus do tipo 1." Arquivos Brasileiros de Endocrinologia & Metabologia 43, no. 2 (March 1999): 96–103. http://dx.doi.org/10.1590/s0004-27301999000200005.
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Objetivo: Analisar a associação da variabilidade da pressão arterial auscultatória sistólica (PAS) e diastólica (PAD) com variáveis clínicas do diabetes tipo 1 (DM1). Métodos: Foram estudados 58 pacientes com DM1 (33 mulheres) com 24,6±8,5 (9-43) anos e duração do diabetes de 8,4±6,6 (0,4-36) anos, sendo 46 adultos e 12 púberes. A PAS e a PAD foram aferidas em três diferentes dias na posição supina, antes e após 5 e 10 min de repouso, calculando-se o coeficiente de variação médio (CVM) e intra-individual (CVI). Resultados; O CVM da PAS entre os diferentes tempos de aferição variou de 3,0 a 3,6% (adultos) e 3,3 a 4,6% (púberes) e o da PAD de 5,5 a 6,6% (adultos) e 6,3 a 7,4% (púberes).O CVM da PAS entre os diferentes dias de aferição variou de 6,4 a 6,8% (adultos) e 8,7 a 9,2% (púberes), sendo o CVI da PAS sem e após 5 min de repouso maior em púberes do que adultos, respectivamente (8,1 ±3,1 vs 5,3±4,1%; p=0,004) e (7,9±4,7 vs 5,2±3,7%; p=0,02) e apresentando uma maior correlação com a idade (PAS antes e após 5 min de repouso, respectivamente r= -0,34; r2= 0,12; p=0,007 e r= -0,31; r2= 0,09; p=0,01. O CVM da PAD entre os diferentes dias de aferição variou de 9,7 a 10,1% para os adultos e de 13 a 14,2% para os púberes. Nos adultos observamos diminuição da PAS e PAD entre os diferentes tempos de aferição e uma maior correlação entre duração do diabetes e PAS final após 5 min (r = 0,39; r2 = 0,15; p=0,007) e PAD após 10 min de repouso (r= 0,36; r2 = 0,13; p= 0,01). Conclusão: A variabilidade da PAS e PAD entre os diferentes dias e tempos de aferição observados neste estudo justificam a necessidade da realização de várias aferições após repouso de até 10 min em ambiente apropriado para o acompanhamento ambulatorial de rotina do paciente com DM1.
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Gilyarov, M. Yu, E. V. Konstantinova, M. R. Atabegashvili, T. D. Solntseva, D. A. Anichkov, А. N. Kostina, R. V. Polybin, A. E. Udovichenko, and A. V. Svet. "Comorbidities and Percutaneous Coronary Intervention in Elderly Patients with Acute Coronary Syndrome." Rational Pharmacotherapy in Cardiology 17, no. 2 (May 7, 2021): 221–27. http://dx.doi.org/10.20996/1819-6446-2021-04-10.
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Aim. To assess comorbidities in elderly patients with acute coronary syndrome (ACS) and to analyze patient subgroups with different treatment strategies in the Regional Vascular Center (RVC).Material and methods. The prospective study included 205 patients with confirmed ACS 75 years and older, the mean age was 81±4.9 years, and 68% were women. ST segment elevation myocardial infarction (STEMI) was diagnosed in 46 (22.4 %) patients, non-ST segment elevation myocardial infarction (NSTEMI) was diagnosed in 159 (77,6 %) patients. The Charlson Comorbidity Index (CCI) was calculated in every patient. Early outcomes were defined as those assessed during hospital stay. Late outcomes were assessed at 6 months after the discharge using phone calls and/or clinic visits. All patients provided written informed consent.Results. Percutaneous coronary intervention (PCI) was performed in 42% of patients. In patients with STEMI and NSTEMI PCI was performed in 73% and 32%, respectively. Mean CCI score was 7.9 points: 7.6 points in men and 8.04 in women. Patients with STEMI had higher CCI score than NSTEMI patients (p<0.01): 8.1 points and 7.1 points, respectively. Patients who underwent PCI had lower CCI score (7.2 points) than patients in non-PCI group (8.2 points; p<0.05). Patients with STEMI in PCI and non-PCI groups had significant difference in CCI score (p<0.05): 7.4 and 8.4 points, respectively. Mean CCI score in patients who died in hospital was 8.5 while discharged patients had 7.6 points (p<0.01). In 6 months 13 patients (6.3%) died, their mean age was 84.9 years, mean CCI was 9 points, PCI was performed in 3 (23%) patients.Conclusions. Elderly patients with ACS had high comorbidity level assessed by CCI score. Higher CCI score was associated with PCI non-performance in elderly patients. Elderly patients with STEMI had higher CCI score than patients with NSTEMI which was significantly associated with PCI non-performance. Patients who died in hospital or in 6 months after the ACS onset had higher CCI score than other elderly patients with ACS.
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You, Benoit, Andrew Clamp, Adrian David Cook, Iain A. McNeish, and Olivier Colomban. "Differential benefit from fractionated dose-dense first-line chemotherapy for epithelial ovarian cancer (EOC) according to KELIM-evaluated tumor primary chemosensitivity: Exploratory analyses of ICON-8 trial." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 5530. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.5530.
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5530 Background: ICON8 phase III trial did not show improvement in PFS or OS with first-line weekly dose-dense chemotherapy in EOC. This analysis evaluated the impact of tumor intrinsic primary chemosensitivity (assessed with modeled CA-125 ELIMination rate constant K (KELIM) based on the CA-125 kinetics during the first 100 days of chemo), on survival by treatment arms. Methods: Retrospective analysis of ICON8 where EOC patients were treated with chemo (Arm 1, standard (std) carboplatin AUC5-6 & paclitaxel 175mg/m2 q3weeks; Arm 2, carboplatin AUC 5-6 q3weeks and weekly paclitaxel 80 mg/m2; or Arm 3, weekly carboplatin AUC 2 & paclitaxel 80 mg/m2; ratio1:1:1) and debulking primary surgery (immediate (IPS), or delayed (DPS)). The association between standardized KELIM (dichotomized as favorable ≥ 1, or unfavorable < 1) and efficacy of treatment arms and surgery completeness was assessed univariate & multivariate analyses. Results: Of 1,566 enrolled patients, KELIM was calculated in 1,004 with ≥ 3 CA-125 available values. KELIM did not differ by treatment arm. Irrespective of surgical strategy, both KELIM and surgery completeness were significant prognostic factors, but treatment arms were not. In 354 IPS patients, 225 had unfavorable KELIM (63%). Weekly dose-dense carboplatin-paclitaxel (Arm 3) (compared to std chemo-Arm 1) was associated with improved survival in unfavorable KELIM patients (PFS:19.6 vs 11.0 months, HR 0.80 [0.54-1.17]; OS : 53.7 vs 40.1 months, HR 0.75 [0.50-1.14]), and worse survival in those with favorable KELIM (PFS: 26.7 vs 48.2 months, HR 1.27 [0.72-2.22]; OS: NR vs 69.2 months, HR 1.05 [0.53-2.06]). Maximum benefit was seen in highest-risk diseases (unfavorable KELIM + incomplete IPS; n = 116; PFS: 17.0 vs 7.4 months, HR 0.49 [0.29-0.82]; OS: 42.6 vs 27.0 months, HR 0.56 [0.33-0.96]). In 611 patients treated with neo-adjuvant chemo +/- DPS (279 unfavorable KELIM, 46%), the same trend for higher survival benefit from dose-dense carboplatin-paclitaxel was found in those with unfavorable KELIM (PFS: 10.8 vs 7.4 months, HR 0.84 [0.63-1.13]; OS: 26.4 vs 23.5 months, HR 0.80 [0.60-1.08]), and reversely. The higher KELIM, the higher the likelihood of complete surgery (OR 4.82 [3.21-7.37]). The prognostic impact of the surgery completeness was greater in unfavorable KELIM patients. Conclusions: In ICON8 trial, both the tumor primary chemosensitivity (by KELIM) and completeness of debulking surgery were major drivers of the prognosis & survival. Dose-dense fractionated chemotherapy in 1st-line setting may be beneficial for patients with lower tumor chemosensitivity, whilst it might be detrimental in those with highly chemosensitive disease. The greatest OS benefit (HR 0.56) from dose-dense chemotherapy was seen in highest-risk diseases (unfavorable KELIM and incomplete IPS).
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Nam, Hannah, Scott C. Roberts, Sajal D. Tanna, and Michael G. Ison. "540. Prolonged Viral Shedding of SARS-CoV-2 In Solid Organ Transplant Recipients." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S337. http://dx.doi.org/10.1093/ofid/ofaa439.734.
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Abstract Background Solid organ transplant (SOT) recipients are more susceptible to viral infection and present with differing viral kinetics when compared to non-immunocompromised cohorts. The duration of viral shedding in SOT recipients with SARS-CoV-2 infection is unknown. Methods All SOT recipients with a diagnosed of SARS-CoV-2 by nasopharyngeal of bronchoalveolar lavage RT-qPCR from March 06, 2020 to May 31, 2020 were identified. Viral shedding duration was obtained by evaluating all subsequent SARS-CoV-2 PCR results following initial positivity over time. Severity classification was defined as mild (outpatient), moderate (hospitalized), and severe (ICU level care). Data were obtained from electronic medical record case review and analyzed with Stata 16. Results 71 patients with a positive SARS-CoV-2 PCR test were identified. 50 (70.4%) were classified as mild/moderate disease, while 21 (29.5%) had severe disease. Median age was 56.5 (IQR 45 – 61.3) years, and 56.9% (n = 41) were male. Older age was significantly associated with severe disease. A disproportionate number of patients were African American/Black or Hispanic at 72.2% (n=52). Interestingly, Caucasian race was significantly associated with less severe outcomes (p=0.038). The majority of patients were kidney transplant recipients (46, 63.9%), followed by liver (13, 18.1%), heart (6, 8.3%), lung (3, 4.2%), and pancreas (9, 12.5%) with a median duration from transplantation at 5 (IQR 3 – 17) years. Overall mortality was 5.6% (n=4), with all deaths occurring only in those with severe disease (19.1%, n=4). Prolonged viral shedding was observed in few patients, with median duration of SARS-CoV-2 PCR positivity at 32 (IQR 18.5 – 41.0) days. One kidney recipient was observed with up to 64 days of positive SARS-CoV-2 RT-PCR from initial diagnosis despite not developing severe disease. Demographics and Outcomes Duration of Viral Shedding in SOT Patients with COVID-19 Conclusion COVID-19 can lead to significant outcomes in SOT with increased mortality in those with severe disease, as well as prolonged viral shedding. Further studies are needed to elucidate the full duration of viral shedding in this population. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)
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Park, Yong Bok, Jung Ho Park, Seung Won Lee, Tae Wan Jung, Kyoung Hwan Koh, and Jae Chul Yoo. "Does the Dog-Ear or Bird-Beak Deformity Remodel After Rotator Cuff Repair?" American Journal of Sports Medicine 48, no. 7 (May 5, 2020): 1575–82. http://dx.doi.org/10.1177/0363546520915199.
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Background: Dog-ear and bird-beak deformities are common after transosseous-equivalent repair (suture bridge technique). The natural course of deformities after rotator cuff (RC) repair using the suture bridge technique is unclear. The remodeling potential of these deformities has not been investigated. Purpose: To evaluate remodeling and retear rates associated with deformities after RC repair. Study Design: Cohort study; Level of evidence, 3. Methods: Between November 2011 and February 2012, we studied 99 consecutive shoulders. All patients underwent arthroscopic RC repair via the suture bridge technique with or without additional sutures. Two groups were formed: no deformity (n= 46) and deformity (n = 53). Deformity was defined as marginal detachment and protrusion of the RC after repair, involving inappropriate compression of the suture limbs from the anchors. Tendon height was measured from the highest point of the most protruding portion of the cuff to the cortex on semi-coronal magnetic resonance imaging (MRI) scan. Change in tendon height was evaluated on MRI scan at 1 week and 6 months postoperatively. Clinical assessment at every patient visit included the American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder score, and visual analog scale for pain (pVAS) score. Results: No significant differences were found in age, sex, symptom duration, tear size, and preoperative ASES, Constant, and pVAS scores ( P > .05) between the 2 groups. The initial tendon height was 7.4 ± 1.5 mm in the no-deformity group and 9.3 ± 2.0 mm in the deformity group. Follow-up height was 6.3 ± 2.1 mm in the no-deformity group and 6.4 ± 1.6 mm in the deformity group. Mean postoperative tendon heights were 90.1% ± 23.8% of the initial height in the no-deformity group and 73.2% ± 15.1% in the deformity group. Clinical scores (ASES, Constant, and pVAS) were not significantly different between the groups at 6 months. There were 4 shoulders in each group that experienced retearing (types 4 and 5 according to the Sugaya classification) at 6 months postoperatively. There was no difference in retear rate ( P > .999). Conclusion: Most deformities after RC repair were remodeled with no effect on retears. Clinical outcomes were not affected by deformities.
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Kutluk, M. Tezer, and Akif Yeşilipek. "Pediatric Cancer Registry in Turkey 2009-2018 (TPOG & TPHD)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e21510-e21510. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e21510.
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e21510 Background: In Children and adolescents aged 0-14, each year more than 200.000 new cancer cases are expected at global level. For the planning and implementation of an effective pediatric cancer control program, pediatric cancer registries are essential. The long term survival rates have been improved to 85% in high income countries, however it is still less than this in LMICs. This work presents the most updated results of the pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the Pediatric Cancer Registry in 2002. The childhood cancer cases registered between 2009-2018 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 10 years from 2009 to 2018, 15713 cases were registered. For all cases, median age was 6.7 year (0-17; M/F 8838/6867, 3 hermaphrodite, 5 unknown). Age distribution was 0-4 yrs, 40.7%; 5-9 yrs, 24.4%; 10-14 yrs, 23.2%; 15-19 yrs, 11.7%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (4368, 27.8%, 5.4, 2519/1849); Lymphoma & other RES tumors (2996, 19.1%, 9.7, 2012/979, 1 hermaphrodite & 4 unknown); CNS [brain & spinal] (2089, 13.3%, 7.1, 1142/947); Symphatetic system (1243, 7.9%, 2.4, 650/593); Retinoblastoma (358, 2.3%, 1.4, 204/154); Renal (788, 5.0%, 3.3, 369/419); Liver (260, 1.7%, 1.8, 143/117); Malignant bone (1030, 6.6%, 12.6, 566/464); Soft tissue sarcomas (1052, 6.7%, 7.4, 611/441); Germ cell (971, 6.2%, 8.4, 346/622, 2 hermaphrodite, 1 unknown); Carcinoma & other malignant epithelial (462, 2.9%, 13.7, 226/236); Other/non-specific malignant (96, 0.5%, 7.8, 50/46). Five year survival rate was found as 70.8%. Conclusions: This registry has been used widely among health care professionals since its establishment in 2002. Survival rates for children and adolescents has been improved to 70%. This level of survival is at the acceptable level for an upper middle income country. This registry became a useful source for investigator and decision makers at national and international level.
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Hunter, Ann, Prem Mahendra, Keith Wilson, Paul Fields, Gordon Cook, Andrew Peniket, Charles Crawley, et al. "A Randomised, Double-Blind, Placebo Controlled, Multicentre Trial of ATL-104, a Swallowable Mouthwash, in Patients with Oral Mucositis Following Peripheral Blood Stem Cell Transplantion (PBSCT)." Blood 108, no. 11 (November 16, 2006): 45. http://dx.doi.org/10.1182/blood.v108.11.45.45.
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Abstract Mucositis is a serious complication of PBSCT. ATL-104 is a recombinant protein, the L-form of phytohaemagglutinin, a potent mitogenic for epithelial cells of the GI tract, resistant to acid and protease degradation. A prospective, pilot study was conducted to assess the effect of ATL-104 on mucositis in patients receiving high dose melphalan (66%) or BEAM (34%) before an autologous PBSCT. Each dose consisted of 15mL of solution containing 50, 100, or 150mg ATL-104 or placebo. For 3 days prior to chemotherapy and for 3 days following transplantation patients swilled the solution in the mouth for 15–30 seconds and then swallowed. Assessments were made for 28 days following dosing or until discharge, for pain, ulceration and the other factors which contribute to the WHO (World Health Organisation) or WCCNR (Western Consortium Cancer Research Nurses) mucositis scales. The first part of the study used a dose ascending design, commencing with 50 mg ATL-104, with patients randomised 3:1, active:placebo. A safety review was performed after 8 patients at each dose. After completion of the 150 mg cohort, a randomised parallel arm design with all doses and placebo was used (1:1:1:1). In total, 63 patients (46 M, 17 F) were treated; 15/16 patients in each group; 54 received all six doses and were fully assessed. ATL-104 at all doses produced a consistent reduction in duration of all grades of oral mucositis, compared to placebo (no statistical significance testing planned). For WHO grades 3–4, the reduction was 4.4, 4.2 and 3.4 days for ATL-104 50mg, 100mg and 150mg respectively, a fall of between 51%–64%, compared with placebo. There were also reductions in the duration of mucositis on the WCCNR scale. There was a reduction in the duration of ulceration scored 1–4, of 2.7, 0.8 and 2.4 days for ATL-104 50mg, 100mg and 150mg respectively, a fall of between 15–43% compared to placebo. No clear effect of ATL-104 on the incidence of mucositis or patients perception of pain was apparent. ATL-104 was well tolerated at all doses. Conclusion: ATL-104 warrants further investigation in larger, randomised, clinical trials. Placebo ATL-104 50 mg ATL104 100mg ATL-104 150 mg Incidence WHO Grades 3–4 Mucositis (%) 50 46 31 67 Duration WHO Grades 3–4 Mucositis (days/SD) 6.7 (1.5) 2.3 (1.5) 2.5 (1.7) 3.3 (1.7) Incidence WHO Grades 2–4 Mucositis (%) 71 62 77 67 Duration WHO Grades 2–4 Mucositis (days/SD) 6.9 (4.0) 4.0 (2.3) 4.9 (3.6) 4.8 (4.5) Incidence WCCNR Grades 2–3 Mucositis (%) 93 92 85 93 Duration WCCNR Grades 2–3 Mucosits (days/SD) 11.6 (5.3) 8.2 (4.7) 8.1 (4.0) 7.8 (2.5) Incidence of Mouth Ulcers Scored 1–4 (%) 71 62 62 68 Duration Mouth Ulcers Scored 1–4 (days/SD) 6.3 (4.2) 3.6 (2.5) 5.5 (3.8) 3.9 (2.1) Incidence Pain/Soreness 1–10 (%) 77 53 77 83 Duration Pain/Soreness 1–10 (days/SD) 7.4 (4.4) 7.0 (3.9) 5.3 (3.4) 6.4 (3.4)
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Bai, Jinbing, Despina Tsementzi, Pretesh R. Patel, Joseph W. Shelton, Mary Dolan, Jessica Arluck, and Deborah Bruner. "Trajectories of sexual dysfunction and its risk factors in women with gynecologic cancer across radiation therapy and healthy controls." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e24097-e24097. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e24097.
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e24097 Background: Women with gynecological cancer (GynCa) reported an increased risk for acute and long-term sexual dysfunction across cancer treatments, especially radiation therapy (RT). However, limited data exist on the course of sexual dysfunction across RT and its risk factors are unknown. This study sought to characterize women’s sexual dysfunction trajectories and identified risk factors of persistent sexual dysfunction. Methods: Using a longitudinal study design, patient-reported sexual dysfunction, demographic and clinical data were collected. Women receiving RT for GynCa older than 18 years or age, race, and BMI matched healthy controls were enrolled. Female Sexual Function Index (FSFI) was used to assess women’s sexual dysfunction. Patients completed all the questionnaires pre-RT, at the end of RT, 6- and 12-month post-RT. Group-based trajectory modeling was used to identify trajectories of sexual dysfunction and risk factors of persistent sexual dysfunction. Results: Eighty-two patients were analyzed, including 36 GynCa patients receiving RT and 46 healthy post-menopausal women, comprising of 33 Blacks, 44 Whites, and 5 others. Three trajectory groups of sexual dysfunction (total FSFI score) were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). All three trajectory groups were significantly different from each other (p<0.01). Similarly, three trajectories were identified for each of six FSFI domains: desire (low [6.3%], moderate [62.5%], high [31.2%], p<0.01); arousal (low [38.1%], moderate [46.4%], high [15.4%], p<0.01); lubrication (low [49.7%], moderate [44.6%], high [5.7%], p<0.01); orgasm (low [43.8%], moderate [31.3%], high [24.9%], p<0.01); pain (low [25.5%], moderate [64.2%], high [10.3%], p<0.01); and satisfaction (low [8.3%], moderate [61.4%], high [30.3%], p<0.01). Risk factors of sexual dysfunction were high pH (p=0.007) and without chemotherapy (p=0.019). Young women had more arousal (p=0.011); high education level was associated with high arousal (p=0.039); low pH was associated with high arousal (p=0.018) and orgasm (p=0.036). No risk factors were found for desire and satisfaction domains. BMI, surgery, and study cohort (cancer vs healthy) were not predictors of sexual dysfunction trajectories. Conclusions: This study identified three trajectories of sexual dysfunction. Low education, high pH, no chemotherapy, and elder women were risk factors of severe sexual dysfunction. Sexual dysfunction interventions should address these risk factors.
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Amano, T., T. Mori, K. Matsumoto, T. Watanabe, and A. Iritani. "276 THE EFFECT OF CUMULUS CELLS DURING MATURATION ON THE RISE IN THE CONCENTRATION OF INTRACELLULAR Ca2+ ([Ca2+]i) OF PORCINE OOCYTES INDUCEDBY INOSITOL 1,4,5-TRISPHOSPHATE." Reproduction, Fertility and Development 17, no. 2 (2005): 288. http://dx.doi.org/10.1071/rdv17n2ab276.
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Increase of inositol 1,4,5-triphosphate (IP3) in the cytoplasm of mammalian oocytes is said to be responsible for [Ca2+]i oscillation observed in the oocytes immediately after sperm penetration, and the [Ca2+]i oscillation is known to be essential for the development of embryos. On the other hand, cumulus cells have been reported to play an important role in cytoplasmic maturation of oocytes and affecting the embryonic development. To obtain more information about the role of cumulus cells in cytoplasmic maturation, the effects of cumulus cells during maturation on the rise in [Ca2+]i and on the rate of activation of porcine mature oocytes induced by IP3 injection were investigated. The immature porcine oocytes were divided into three groups: COCs (intact cumulus-oocyte complexes), DOs (oocytes denuded of their cumulus cells), Co-culture (DOs attached to separated cumulus cells). These groups of immature oocytes were cultured in NCSU23 46 h for maturation. To examine the function of cumulus cells, two groups of immature oocytes were also prepared: DOs + pyruvate (DOs put into NCSU23 with pyruvate) and COCs-glucose free (COCs put into NCSU23 without glucose). The mature oocytes from each group were loaded with Ca2+ indicator fluorescent dye Fura2-AM, and then were irradiated by 340 nm and 360 nm of ultraviolet immediately after the injection of IP3. The intensities of emission light caused by the irradiation of 340 nm and 360 nm ultraviolet were recorded as E340 and E360. Since coupling of Ca2+ and the dye intensifies E340, but does not change E360, the level of [Ca2+]i was shown as R (ratio = E340/E360) in this study. Activation rate was calculated by counting the number of the oocytes that formed pronuclei by injection of IP3. ANOVA and Student's t-test were used in this study. Transient rise in [Ca2+]i was observed in the mature oocytes from every group. The peak R of the rise in [Ca2+]i of the mature oocytes derived from COCs, Dos, and Co-culture and induced by IP3 were 7.2, 4.0, and 6.9, respectively. The R of DOs was significantly lower than those of the others (P < 0.05). Also, the activation rate of the mature oocytes from DOs was significantly lower than those from COCs and Co-culture (31, 66, and 66%). The mature oocytes from DOs + pyruvate showed the same level of peak R compared with those from COCs (7.4 and 6.3), but COCs-glucose free showed a slight but significantly lower peak R compared with the mature oocytes from COCs (6.0 and 7.4, P < 0.05). In conclusion, cumulus cells appeared to support the rise in [Ca2+]i of porcine oocytes induced by IP3 during maturation and the following activation. Moreover, a function of cumulus cells supposedly produces pyruvate by metabolizing glucose and provides it to oocytes during maturation for promoting the cytoplasmic maturation. A part of this study was supported by a Grant-in-Aid for the 21st Century COE Program of the Japan MEXT, and by a grant from the Wakayama Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence of the JST.
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Korsakova, Yu L., T. V. Korotaeva, E. Yu Loginova, E. E. Gubar, E. A. Vasilenko, A. A. Vasilenko, N. A. Kuznetsova, I. M. Patrikeeva, and E. L. Nasonov. "The prevalence of comorbid and concomitant diseases in psoriatic arthritis patients, data from Russian register." Rheumatology Science and Practice 59, no. 3 (July 15, 2021): 275–81. http://dx.doi.org/10.47360/1995-4484-2021-275-281.
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Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis associated with psoriasis (Ps); it belongs to the group of spondyloarthritis and is accompanied by damage to both the spine and peripheral joints, as well as the development of enteritis and dactylitis. In addition to skin and joint damage, PsA has numerous comorbid conditions that are pathogenetically related to the underlying disease, such as inflammatory bowel disease (IBD) and autoimmune eye disease, as well as cardiovascular diseases, obesity and metabolic syndrome, diabetes, osteoporosis, malignancies, mental disorders, and various concomitant diseases. We present data of the prevalence of these pathological conditions among the cohort of PsA patients included in the Russian register.Objective – to study the prevalence of comorbid and concomitant diseases in PsA patients.Materials and methods. The Russian multicenter, observational study with retrospective and prospective data collection of PsA patients included 614 patients with the established diagnosis psoriatic arthritis, corresponding to the CASPAR criteria, from 39 subjects of the Russian Federation, female/male – 331 (54%)/283 (46%). The average age was 45.2±0.52 years, duration of PsA – 5.7±0.27 years, Ps – 15.71±0.56. Duration of observation period: January 2016 – November 26, 2019. The diagnosis of comorbid and concomitant diseases was confirmed by medical specialists in accordance with the ICD-10 code. The analysis of the frequency and structure (%) of these diseases was carried out.Results. The majority of PsA patients had limited Ps: the area of Ps skin lesion (BSA, Basic Surface Area) was less than 3% in 372 (61.5%) patients, BSA from 3% to 10% – in 185 (30.6%), BSA>10% – in 47 (7.8%). Comorbid and concomitant diseases were detected in 297 (48%) of 614 patients. 183 (61.6%) patients had 2 or more diseases in addition to Ps and PsA. Diseases of the circulatory system were detected in 229 (77.1%) PsA patients with comorbid and concomitant diseases (arterial hypertension – in 194 (65.3%), coronary heart disease – in 22 (7.4%)). Diseases of the endocrine system, metabolic disorders were detected in 156 (52.5%) patients with PsA (diabetes mellitus in 44 (14.8%), hyperlipidemia in 44 (14.8%), metabolic syndrome in 36 (12.1%), obesity in 7 (2.4%), and others). Gastrointestinal diseases were observed in 62 (20.9%) patients. Diseases of the biliary system – in 33 (11.1%) patients. Diseases of the musculoskeletal system and connective tissue that are not associated with PsA – in 44 (14.8%). Diseases of the genitourinary system – in 23 (7.7%) patients. Respiratory diseases – in 17 (5.7%) patients. Infectious diseases – in 11 (3.7%). Eye diseases were detected – in 10 (3.4%) patients. Hematological diseases were diagnosed in 6 (2.0%) patients. Depression – in 4 (1.3%) patients.Conclusions. Among 297 patients with PsA with comorbid and concomitant diseases, diseases of the circulatory system are the most common (in 77.1%), less often – diseases of the endocrine system, metabolic disorders (in 52.5%) and diseases of the digestive system (in 32%). Uveitis (2.7%), IBD (1.3%), and depression (1.3%) were rarely detected in our cohort. The majority of patients in the Russian registry had mild forms of Ps (61.5%), and severe Ps (BSA>10%) was observed only in 7.8%. Thus, PsA is associated with a high prevalence of comorbid and concomitant diseases, especially cardiovascular. When choosing a treatment, these diseases should be taken into account. In connection with the new possibilities of therapy, it is necessary to evaluate the potential impact of therapy on patients with comorbid and concomitant diseases in real clinical practice.
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Hakim, Frances T., Najibah Rehman, John Dickinson, Sivasubramanian Baskar, Christoph M. Rader, Edward W. Cowen, Steven Z. Pavletic, and Ronald E. Gress. "Elevated BAFF Is Correlated with Inflammatory Processes in Chronic Graft Versus Host Disease and Supports Increases in Transitional B Cells." Blood 112, no. 11 (November 16, 2008): 465. http://dx.doi.org/10.1182/blood.v112.11.465.465.
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Abstract B Cell Activating Factor of the TNF Family (BAFF) plays a critical role in the survival, activation and function of B cells. Elevated levels of BAFF in plasma, however, have been reported in systemic autoimmune disorders and in chronic graft versus host disease (CGVHD). We similarly observed elevated plasma BAFF levels in 98 patients in an ongoing NCI CGVHD natural history protocol, with a median of 2653 pg/ml (range 92 to 14907), as compared to 556 pg/ml (range 75 to 1834) in 18 normal donors. Furthermore, in a subset of 40 patients in which severity of cutaneous CGVHD could be assessed by the presence of marked erythema or sclerosis, BAFF levels correlated with total percentage body surface area involvement (p<0.02). We then explored the factors that might contribute to elevated BAFF levels. In recipients recovering from either autologous or allogeneic transplant (without GVHD) we observed the highest BAFF levels at day 0 (median of 10534 and 12240 pg/ml respectively), when B cells were severely depleted. As B cell populations recovered to normal levels post transplant, plasma BAFF concentrations declined (Spearman r = −.80 and r = −.60, respectively), consistent with homeostatic cytokine-consumption dynamics. Despite comparably high levels of BAFF (median of 11342 pg/ml) at transplant day 0 in 16 patients who later developed CGHVD, BAFF levels in the cross-sectional, natural history patient population were only moderately correlated with the degree of post transplant B cell recovery (r = −.46). Since inflammatory triggers can induce elevated BAFF production, we assessed plasma levels of cytokines indicative of an inflammatory process. In 98 patients, the plasma levels of IP-10 and sTNFRII correlated positively with BAFF levels (r = +.579 and r = +.396, respectively), consistent with active inflammatory processes in those CGVHD patients with elevated BAFF levels. In a multi-step regression model, the levels of circulating B cells, plasma IP-10 and sTNFRII combined to strongly predict BAFF levels (R =.704). These findings suggest that both homeostatic recovery of B cell populations consuming BAFF and inflammatory cytokine cascades initiated by donor-anti-host reactivity combine to regulate BAFF levels post transplant. Although a broad range of autoimmune symptoms have been described in CGVHD, the mechanisms by which donor-anti-host reactivity can result in autoimmunity remains poorly understood. In murine models, elevated BAFF levels have been associated with increased survival of the transitional B cell population, altering the normal processes of B cell negative selection, and resulting in failure to eliminate auto-reactive B cells. We therefore assessed whether elevated BAFF levels were associated with increased frequencies of transitional CD21− T1 B cells in CGVHD patients. In 79 CGVHD patients, the median percentage of CD19+CD21− transitional B cells was 6.13% (range 1% to 39.4%) as compared to 2.24% (range 0.66% to 7.44%) in 40 healthy adult donors. Furthermore, the frequency of CD21− transitional B cells was significantly higher in those patients with higher BAFF levels (p<.002). Finally, the expression (mean fluorescent intensity (MFI)) of the BAFF receptor (BAFF-R) was reduced in patients with CGVHD compared with normal donors, consistent with down-regulation upon BAFF consumption; among CGVHD patients, receptor MFI was inversely correlated with BAFF levels (Spearman r = −.44). Elevated BAFF levels in CGVHD therefore may both reflect the inflammatory processes initiated by donor-anti-host reactivity and contribute to the later generation of pathologic autoantibodies by dysregulation of B cell negative selection.
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Nikiphorou, E., P. Carvalho, A. Boonen, B. Fautrel, P. Richette, P. M. Machado, D. Van der Heijde, R. B. M. Landewé, and S. Ramiro. "POS0238 SICK LEAVE AND ITS PREDICTORS IN EARLY AXIAL SPONDYLOARTHRITIS: THE ROLE OF CLINICAL AND SOCIOECONOMIC FACTORS. FIVE-YEAR DATA FROM THE DESIR COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 340.2–340. http://dx.doi.org/10.1136/annrheumdis-2021-eular.723.
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Background:Sick leave (SL) represents an often poorly studied adverse work outcome especially in early axSpA, with speculation around the potential role of clinical and socioeconomic (SE) factors.Objectives:To investigate the occurrence of SL and the impact of clinical and SE factors on SL in early axSpA.Methods:Patients with a clinical diagnosis of axSpA from the DESIR cohort up to 5 years of follow-up (6-month visits in the first 2 years, followed by annual visits) were studied. Time to SL and potential baseline and time-varying predictors were explored, with a focus on SE variables: age, gender, smoking status since last visit, ethnicity (Caucasian vs other), job type based on ‘collar’ (blue vs white), educational status (low vs high -university), marital status (married vs not) and parental status (number of children); and clinical factors including disease activity (ASDAS/BASDAI), function (BASFI), mobility (BASMI), at each time point. The incidence of SL was calculated as the number of SL events over the total number of person-days under observation. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable Cox survival model building.Results:In total, 704 axSpA patients with work-related data were included in this study: mean (SD) age 33.8 (8.6); 46% male. At baseline, 80% of patients were employed; of these, 5.7% reported being on SL, with people shifting in and out of different work states over time. The distribution of first and recurrent SL episodes over time is shown in the figure 1. The incidence of SL amongst those at risk (n=620, 88%) and across the five years of DESIR was 0.05 (95% CI 0.03, 0.06) per 1000 days calculated in a total of 913,559 observed person-days. In survival analyses, 7% (n=43) of those at risk developed SL at some point. Mean (SD) time to SL was 806 (595) days (min 175, max 2021 days). In people who developed SL, 25% did so at 364 days; 50% and 75% at 545 and 1172 days, respectively. Significant differences were seen between baseline socio-demographic, clinical variables and treatment in patients who developed SL at any point, compared to those who did not. In multivariable models (Table 1) older age, higher disease activity, smoking and use of TNFi, the latter likely a proxy to worse disease, were all significantly associated with more SL. Male gender and higher education were associated with less SL. There were no relevant interactions between SE factors and clinical variables.Table 1.Univariable and multivariable model analyses with Sick Leave as outcome.Type of analysisUnivariable analysisMultivariable modelHR (95% CI)HR (95% CI) (N = 614)Explanatory variablesAge1.04 (1.01, 1.08)1.05 (1.01, 1.09)Male gender0.37 (0.19, 0.74)0.41 (0.20, 0.86)High education0.33 (0.17, 0.61)0.48 (0.24, 0.95)Marital status2.44 (1.12, 5.27)NSASDAS (CRP)1.83 (1.34, 2.50)1.49 (1.04, 2.13)BASFI, 0-101.24 (1.09, 1.40)*BASMI, 0-101.76 (1.31, 2.38)*Comorbidity count1.77 (1.22, 2.57)NSHLA-B27 positive0.51 (0.28, 0.93)NSSmoking (current vs not)2.40 (1.31, 4.37)2.55 (1.32, 4.91)NSAID score last week, 0-4001.01 (1.00, 1.01)NSOral Corticosteroid use (vs no)3.90 (1.80, 8.46)NSTNF use2.86 (1.55, 5.28)2.41 (1.27, 4.58)*Variables tested in models separate from ASDAS. NS=Not significant in multivariable model.Figure 1.Distribution of first and recurrent sick leave episodes over time in the study population at risk.Conclusion:In this early axSpA cohort of young, working-age individuals, older age and worse disease activity were associated with more SL, whereas male gender and higher education were associated with less SL. The findings suggest a role of SE factors such as gender and level of education in adverse work outcomes, alongside active disease.Disclosure of Interests:None declared
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Shahzad, Moazzam, Sibgha Gull Chaudhary, Ezza Tariq, Naira Fatima, Muhammad Arslan, Muhammad Usman Zafar, Amna Y. Shah, et al. "Outcomes with Mismatched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced Intensity Conditioning: A Systematic Review and Meta-Analysis." Blood 138, Supplement 1 (November 5, 2021): 2863. http://dx.doi.org/10.1182/blood-2021-146051.
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Abstract Background: Allogeneic hematopoietic cell transplantation (HSCT) is often the optimal and only potentially curative therapy in several high-risk hematologic malignancies. Although human leukocyte antigen (HLA)-matched donors remain the preferred choice for HSCT recipients, haploidentical and umbilical cord blood HSCT has increased access to transplantation. Despite these advances, many patients lack an appropriate donor, in particular the ethnic minorities. The use of mismatched unrelated donors (MMUD) has increased over the years but concerns regarding increased risk of graft versus host disease (GVHD) and non-relapse mortality (NRM) limits the utility of MMUD HSCT. The intensity of the conditioning regimen has a significant impact on survival in case of mismatched donors. We conducted a systematic review and meta-analysis aimed to investigate the outcomes with MMUD HSCT using reduced intensity conditioning (RIC). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Library, and ClinicalTrials.gov) from date of inception through February 2021 using the MeSH and entry terms for "hematopoietic stem cell transplantation", OR "hematologic neoplasms", AND unrelated donors" AND "treatment outcome". A total of 2477 records were identified and primary and secondary screening was done. After excluding review, duplicate, and non-relevant articles, we included 6 (4 retrospective, 2 prospective) studies reporting outcomes following RIC MMUD HSCT. The Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data and randomized control trial was used for quality assessment, and all studies were reported as good. Proportions along with a 95% confidence interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). The variance between the studies was calculated using Der Simonian Laird Estimator. Results: We identified 895 participants in the 6 studies, who had MMUD HSCT with RIC. (Table 1) Median age was 57.5 (18-76) years and 56% (n= 415) were males as reported by four studies (n=740). In five studies with available data (n=855), source of the primary graft was peripheral blood (PB) and bone marrow (BM) in 72% (n=614) and 28% (n=241) of the HSCT recipients respectively. After a median follow-up of 48 (3-125) months, we estimated a pooled overall survival (OS) of 62% (95% CI 0.52-0.72, I 2=84%, n=895) at one year and 43.5% (95% CI 0.33-0.54, I 2 =84% n=855) at three years. The pooled incidence of acute GVHD (grade II-IV), acute GVHD (grade III-IV), and chronic GVHD were 37% (95% CI 0.26-0.49, I 2=81%, n=610), 16% (95% CI 0.07-0.29, I 2=87%, n=542), and 28% (95% CI 0.13-0.47, I 2=95%, n=848) respectively. Progression free survival (PFS) and relapse rates (RR) were 46% (95% CI 0.30-0.62, I 2=92%, n=814) and 31% (95% CI 0.24-0.39, I 2=65%, n=814) respectively. The pooled incidence of non-relapse mortality (NRM) was 23% (95% CI 0.09-0.40, I 2=91%, n=707). Kasamon et al. and Shaw et al. reported 1-year OS of 75-79% with MMUD HSCT using fludarabine, cyclophosphamide and 2 Gy total body irradiation RIC, bone marrow graft and post-transplant cyclophosphamide, sirolimus and mycophenolate for GVHD prophylaxis. Conclusion: Mismatched unrelated donor HSCT has shown favorable outcomes with reduced intensity conditioning using a post-transplant cyclophosphamide-based regimen, comparable to the historical outcomes with mismatched related donor (haploidentical) HSCT. MMUD HSCT with RIC can be considered in patients lacking an HLA-matched donor. This strategy will expand access to HSCT in patients with ethnic minorities who often lack a matched donor. Figure 1 Figure 1. Disclosures McGuirk: EcoR1 Capital: Consultancy; Allovir: Consultancy, Honoraria, Research Funding; Gamida Cell: Research Funding; Novartis: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Fresenius Biotech: Research Funding; Bellicum Pharmaceuticals: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.
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Chen, L. F., X. Zhang, C. Chen, J. D. Ma, Y. Mo, J. Lin, Y. Y. Zou, D. H. Zheng, and L. Dai. "AB0125 CLINICAL CHARACTERISTICS OF RHEUMATOID ARTHRITIS PATIENTS WITH IGG4-RELATED SYNOVITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1091.2–1092. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2245.
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Background:Elevated serum IgG4 (sIgG4) and IgG4+ plasma cell tissue infiltration are outstanding features of IgG4-related disease (IgG4-RD). However, elevated IgG4 is not specific for IgG4-RD. Our previous study reported elevated sIgG4 in 46% of rheumatoid arthritis (RA) patients (Mediators Inflamm 2014). Whether synovium from RA patients show similar characteristics of IgG4-RD and how about the clinical characteristics of RA patients with IgG4-related synovitis have not been reported yet.Objectives:To explore the serum and synovial IgG4 level and their correlation with disease indicators in RA.Methods:Active RA patients who underwent needle synovial biopsy with qualified synovium tissue were recruited. Demographic and clinical data were collected simultaneously. Synovium tissue were stained with H&E for Krenn synovitis score and immunohistochemistry for positive cell densities of CD20, CD38, IgG and IgG4. Serum IgG4 level was detected by immunonephelometry.Results:Among 96 RA patients recruited, 74 (77.1%) were female, the median age was 55.0 (46.0~61.0) years, disease duration was 42.0 (12.0~120.0) months and SDAI was 31.2 (22.1~42.8).The median sIgG4 was 1.38 (0.86~2.42) g/L and 49(51.0%) patients had elevated sIgG4. Compared with those with normal sIgG4, RA patients with elevated sIgG4 had significantly higher levels of PrGA [7 (5~8) vs. 6 (4~7)], ESR [90 (64~116) mm/h vs. 61 (38~75) mm/h], CRP [46.20 (17.20~74.20) mg/L vs. 18.90 (9.46~49.20) mg/L], DAS28-ESR [6.3 (5.6~7.4) vs. 5.7 (4.7~6.4)], SDAI [34.2 (25.3~48.8) vs. 27.8 (18.9~35.9)] and HAQ-DI [1.70 (0.61~2.28) vs. 0.88 (0.40~1.75), all P<0.05]. Meanwhile, they also showed significantly higher synovial counts of CD38+ plasma cells [1240(559~2290) /mm2 vs. 1020(354~1777) /mm2], IgG4+ plasma cells [106 (39~249) /mm2 vs. 68 (3~123) /mm2], and higher ratio of IgG4+/IgG+ plasma cells [26.3 (15.5~38.0) % vs. 15.2 (0.9~24.7) %, all P<0.05].The median IgG4+ plasma cells count was 83 (10~192) /mm2 and median ratio of IgG4+/IgG+ plasma cells was 19.1 (8.4~31.5)%. Both of them correlated positively with ESR, CRP and sIgG4 (r=0.216~0.394, all P<0.05). There were 46 (47.9%) patients with IgG4+ plasma cells >10/HPF, who had significant higher ESR [86 (50~109) mm/h vs. 65 (40~84) mm/h] and CRP [43.35 (16.93~77.85) mg/L vs. 26.15 (9.54~52.53) mg/L, both P<0.05] than those with IgG4+ plasma cells ≤10/HPF. There were 13 (13.5%) patients with the ratio of IgG4+/IgG+ plasma cells >40%, and 11 (11.5%) patients with both IgG4+ plasma cells >10/HPF and IgG4+/IgG+ plasma cells ratio >40% (IgG4-related synovitis). RA patients with IgG4-related synovitis had significant higher ESR than the others [106 (53~125) mm/h vs. 69 (41~91) mm/h, P<0.05].There were 10 (10.4%) patients showing elevated sIgG4 and IgG4-related synovitis. Four patients completed 1-year follow-up and all of them achieved remission at 6th month (SDAI≤3.3, Figure 1). Only one patient had radiographic progression at 12th month.Figure 1.Dynamic disease activity of 4 RA patients with elevated sIgG4 and IgG4-related synovitis during 1-year follow-up.Conclusion:IgG4-related synovitis can be found in RA patients. Their clinical significance in disease characteristics and outcomes are worth further study.Acknowledgements:This work was supported by National Natural Science Foundation of China (no. 81971527, 81801606 and 81801605), Guangdong Natural Science Foundation (no. 2018A030313541 and 2018A030313690), Guangdong Medical Scientific Research Foundation (no. A2018062), Guangdong Basic and Applied Basic Research Foundation (no. 2019A1515011928 and 2020A1515110061), and Science and Technology Program of Guangzhou (no. 201904010088).Disclosure of Interests:None declared
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Fuji, Shigeo, Sung-Won Kim, Shin-ichiro Mori, Shigemi Kamiya, Takahiro Fukuda, Satoshi Yamazaki, Ryuji Tanosaki, Kensei Tobinai, and Yoichi Takaue. "Hyperglycemia during Neutropenia Was Associated with the Risk of Infection and Organ Dysfunction in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)." Blood 108, no. 11 (November 16, 2006): 5308. http://dx.doi.org/10.1182/blood.v108.11.5308.5308.
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Abstract Background Recipients of allogeneic HSCT frequently require support with total parenteral nutrition (TPN), in expense of increased risk of infections associated with hyperglycemia, particularly in neutropenic period. Previously, van den Berghe et al. showed that intensive insulin therapy reduced the morbidity including infections and mortality in patients cared in the ICU. Here we assessed the clinical impact of hyperglycemia in patients undergoing myeloablative HSCT. Methods A retrospective cohort of consecutive 112 adults treated between January 2002 and June 2006 was reviewed, and 21 patients were excluded due to coexisting infectious diseases, preexisting neutropenia or graft failure. The remaining 91 patients with various hematological malignancies were categorized according to mean blood glucose (BG) level, which developed in neutropenic period, to 1) “normoglycemia” (BG≤110 mg/dl, n=28), 2) “mild hyperglycemia” (110<BG≤150 mg/dl, n=49) and 3) “moderate hyperglycemia” (150 mg/dl<BG, n=14). Conditioning regimens included BU/CY (n=45), CY/TBI (n=43) and CA/CY/TBI (n=3). GVHD prophylaxis included cyclosporine- (n=62) and tacrolimus-based regimen (n=29). Stem cell sources included bone marrow (n=46), peripheral blood (n=41) and cord blood cells (n=4). Infection prophylaxis was oral ciprofloxacin, acyclovir and fluconazole. The primary endpoint of this study was the occurrence of febrile neutropenia (FN) and infectious episodes including bacteremia, pneumonia and central venous catheter infection. The secondary endpoint was abnormal laboratory data as parameters for organ dysfunction, which were used in the study by van den Berghe, including elevation of serum creatinine ≥2.0 mg/dl or more than twice of the baseline, serum total bilirubin ≥2.0 mg/dl and serum C-reactive protein (CRP) ≥15 mg/dl. For statistical analysis, student T, chi-square, and Wilcoxon rank-sum tests were used. Results There was no essential difference between the 3 groups in the average caloric intake, occurrence of FN and infectious episodes. However, hyperglycemia was significantly associated with higher number of febrile days (normoglycemia 3.3±3.7 days; mild hyperglycemia 5.5±4.1days p=0.017; moderate hyperglycemia 7.4±5.0days: p=0.004), hypercreatininemia (normoglycemia 3.6 %; moderate hyperglycemia 28.6% OR 10.8, p=0.018), hyperbilirubinemia (normoglycemia 10.7 %; moderate hyperglycemia 42.9% OR 6.3, p=0.017), CRP ≥15 mg/dl (normoglycemia 14.3 %; moderate hyperglycemia 64.3% OR 10.8, p<0.001), longer hospital stay (normoglycemia 43.0±20.5 days; mild hyperglycemia 60.7±31.3 days: p=0.003, moderate hyperglycemia 77.8±51.3 days; p=0.004) and in-hospital mortality (normoglycemia 0%, mild hyperglycemia 10.2%; p=0.08, moderate hyperglycemia 21.4%; p<0.001). Conclusion Hyperglycemia during neutropenia was associated with increased risk of infection and organ dysfunction, which further lead to vicious cycle of infectious complications. The results may support the possibility that intensive glucose control reduces the morbidity including infectious complications and organ dysfunction after HSCT.
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Alali, Muayad, Allison Bartlett, Lara Danziger-Isakov, and Lara Danziger-Isakov. "64. Absolute Monocyte Count (AMC) as Early and Safe Marker for Discharge in Low-risk Pediatric Febrile Neutropenia with Cancer." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S150—S151. http://dx.doi.org/10.1093/ofid/ofab466.266.
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Abstract Background Fever with neutropenia (FN) is common and the timing of antibiotic cessation in patients without an identified fever source is uncertain. Absolute neutrophile count (ANC) recovery has been used clinically to represent bone marrow recovery (BMR) but other options should be considered. We hypothesized that absolute monocyte count (AMC), and absolute phagocyte count (APC) are more sensitive, and an earlier safe marker of antibiotic cessation (AC) compared with ANC Methods A retrospective review was performed for FN episodes (FNEs) at UCM Comer Children’s Hospital between 2009 and 2016 in pediatric oncology patients. Eligible FNEs who were a febrile for 24 hours, had no bacterial source identified at time of AC, and did not receive chemotherapy 10 days following AC. Ten-day post-AC outcomes, length of stay and cost were assessed and compared among different BMR parameters (ANC vs AMC). Results A total of 928 FN episodes (FNEs) were identified. 391 eligible FNEs occurred in 235 patients. Three groups were compared based on ANC (cells/μL) at the time of AC : < 200 in 102 (26%), 200-500 in 111 (28%), and >500 /uL in 178 (46%) (Figure1) with an overall ten-day recurrent fever rate 7.4% (29/391) and readmission rate of 5.6% (22/391). No significant differences in recurrent fever rates were identified among 3 ANC groups (11.7%, 6.3% and 5.6% respectively, P=0.08) and readmission (10%,4.5%, 4%, respectively; P=0.07)(Table 1).In subset analysis of AMC for each ANC group, patients with AMC >100 at AC have favorable outcomes, regardless ANC threshold (P< 0.01) (Table 1). Median of length of stay of FN was 3 days shorter using AMC >100/uL for BMR compared with any threshold of ANC (P< 0.01) and decrease overall FN cost stay (P< 0.01) (Table 2). Similar analysis show APC >300/uL at time of AC has favourable outcomes and decrease LOS regardless ANC threshold (data not shown here). Conclusion Our results suggest that a AMC > 100 /uL regardless of ANC/uL, is a safe threshold value for empiric AC and discharge. This approach may shorten length of stay, reduce burden of cost of febrile neutropenia cost and potential long term antibiotics side effects. Disclosures Lara Danziger-Isakov, MD, MPH, Ansun (Individual(s) Involved: Self): Scientific Research Study Investigator; Astellas (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Pfizer (Individual(s) Involved: Self): Scientific Research Study Investigator; Shire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Viracor: Grant/Research Support
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Korsakova, Y., E. Loginova, E. Gubar, E. Vasilenko, A. Vasilenko, N. Kuznetsova, I. Patrikeeva, T. Korotaeva, A. Lila, and E. Nasonov. "SAT0424 OBESITY LINKS TO PSORIATIC ARTHRITIS (PsA) ACTIVITY, HIGHER PREVALENCE OF CARDIOMETABOLIC DISORDERS AND WORSE PATIENT REPORTED OUTCOMES (PROs): DATA FROM THE RUSSIAN PsA REGISTRY (RU-PsART)." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1166.2–1166. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5538.
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Background:PsA patients (pts) have an increased risk of cardiovascular (CV) and metabolic (Met) disorders due to the combination of inflammation and increased prevalence of traditional CV risk factors. Only limited data are available on Russian PsA pts. Data was collected from 25 rheumatology clinics of the Russian FederationObjectives:to study, in clinical practice, the prevalence of obesity and its association with PsA activity, CV/Met comorbidities and PROsMethods:614 (M/F=331(54%)/283(46%) PsA pts fulfilling the CASPAR criteria were included from the RU-PsART cohort. Mean age 45.2±0.52 yrs, PsA duration 5.7±0.27 yrs, PsO duration 15.71±0.56 yrs, DAPSA 28.79±0.75. At baseline (BL) PsA activity was evaluated by Tender Joint Count (TJC68), Swollen Joint Count (SJC66), PGA, physician global assessment by Visual Analog Scale (VAS), DAPSA; PROs according to PtGA VAS, PtPain VAS, HAQ, Work Productivity and Activity Index (WPAI) and Body Mass Index (BMI, kg/m2) were calculated. All pts were split into three groups by BMI (kg/m2): normal<25 (I group), overweight 25-30 (II group), obese>30 (III group). M±m, %, Me [Q25; Q75], χ2or Fischer’s exact tests were performedResults:At BL the BMI was 27.7±0.23 kg/m2with the following BMI categories: normal - 213 pts (34.7%), overweight - 214 pts (34.8%) and obese - 187 (30.5%). Increased BMI was observed in 65.3% of PsA pts. In all groups, comorbidities were found in 297 out of 614 pts (48%): arterial hypertension in 190 (64%), diabetes mellitus in 44 (14.8%), Met syndrome in 36 (12.1%), Coronary Heart Disease in 22 (7.4%). CV and Met disorders were significantly more common in obese pts with BMI>30 compared to overweight pts and to normal BMI pts; female prevailed (Table 1).Table 1.CV/Met comorbidity in three groups, n (%).I groupBMI<25 kg/m2II groupBMI 25-30 kg/m2III groupBMI>30 kg/m2pArterial hypertension28(13.2)55(25.7)85(46.5)р<0.0001*Diabetes mellitus015(7)25(14)р<0.0001**Metabolic syndrome0(0)6(2.8)23(12.8)р<0.0001**Coronary heart disease2(0.9)6(2.8)10(5.6)р<0.026****III vs I and II groups, ** III vs II, *** III vs I groupAt BL pts with BMI>30 had higher PsA activity by DAPSA, HAQ, daily activity impairment by WPAI, PtPin compared to I and II groups (table 2).Table 2.PsA activity and PROs based on BMI categories.I groupBMI<25 kg/m2II groupBMI 25-30 kg/m2III groupBMI>30 kg/m2pDAPSA22.7 [14.7; 35.8]24.9 [13.5; 38.5]27 [17.2; 44.4]р<0,05*HAQ0.9 [0.5; 1.3]0.9 [0.5; 1.3]1 [0.8; 1.6]р<0,05*Daily activity impairment0.3 [0; 0.5]0.3 [0; 0.5]0.4 [0; 0.6]р<0,05*PtPain, mm VAS50 [30; 66.5]50 [30; 68]50 [40; 70]р<0,05***p<0.05 III vs I and II groups, ** p<0.05 III vs II groupConclusion:In clinical practice, BMI increase was found in the majority of PsA pts. Obesity was associated with higher PsA activity, more prevalence of CV/Met disorders and worse PROs. Obesity requires a change of the pts’ lifestyle, nutrition correction and a right choice of therapyDisclosure of Interests:Yulia Korsakova: None declared, Elena Loginova Speakers bureau: Janssen, ELENA GUBAR: None declared, Elizaveta Vasilenko: None declared, Aleksey Vasilenko: None declared, Natalia Kuznetsova: None declared, Irina Patrikeeva: None declared, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Alexander Lila: None declared, Evgeny Nasonov: None declared
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Pieri, Lisa, Emanuela Sant'Antonio, Elisa Rumi, Paola Guglielmelli, Rajmonda Fjerza, Chiara Paoli, Lucia Merli, Mario Cazzola, and Alessandro M. Vannucchi. "IWG-MRT 2013 Criteria-Based Assessment of Response Among 83 Patients with Myelofibrosis Treated with JAK Inhibitors: Experience of Two Centers." Blood 126, no. 23 (December 3, 2015): 1615. http://dx.doi.org/10.1182/blood.v126.23.1615.1615.
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Abstract Introduction. Ruxolitinib is a JAK inhibitor (JAKi) approved for myelofibrosis (MF) patients (pts), while other JAKi are being tested in clinical trials. The IWG-MRT response criteria (RC) used to evaluate drug efficacy were revised on 2013 and adapted to take into account efficacy in specific aspects of the disease, duration of response and toxicities (Blood 2013;122:1395). Methods. We retrospectively evaluatedthe response rate in MF pts treated for at least 3 months (mo) with JAKi in phase II/III and expanded access trials at University of Florence and Pavia, according to IWG-MRT 2013 RC. We also collected molecular data, last follow up and reasons of discontinuation. Changes in spleen size (SS) were evaluated only by palpatory speen length measurement from the left costal margin without confirmation by MRI or CT scan and symptomatic improvement evaluation was present/absent (no grading). Results. We collected 83 pts, 66 treated with ruxolitinib (79.5%), 12 fedratinib (14.5%), 3 pacritinib (3.6%), 2 gandotinib/LY2784544 (2.4%). At enrolment, the 4 groups did not differ for gender, age, MF diagnosis (primary or secondary to polycythemia vera or essential thrombocythemia), DIPSS, DIPSS-plus, JAK2V617F, MPLW515 and CALR mutational status, and JAK2V617F allele burden. 64 cases (77%) were evaluated for high molecular risk status (HMR; at least one mutation in EZH2, ASXL1, IDH1/2 and SRSF2 genes): 22/64 (34.4%) were HMR with no differences among groups. Of the 3 pacritinib pts, one carried SRSF2 and one both EZH2 and ASXL1 mutation. At baseline, median hemoglobin (Hb, g/dL) levels were lower for fedratinib and pacritinib group: 11.5 (range 7-15.5) for ruxolitinib, 10 (7.4-13.3) for fedratinib, 8.1 (8-8.3) for pacritinib and 11.9 ( 11.9-12) for gandotinib (p=0.012). All pacritinib treated pts were red blood cell transfusion dependent, compared to 10.6% in ruxolitinib (7/66), 8.3% in fedratinib (1/12) and none in gandotinib (p<0.001). Median platelet count (PLT, x10^9/L) was: 245 (range 52-603) for ruxolitinib, 153 (70-610) for fedratinib, 28 (27-119) for pacritinib, 170 (154-187) for gandotinib (p=0.065). Median SS was 14 cm (range 0-35) for ruxolitinib, 23 (10-36) for fedratinib, 20 (17-26) for pacritinib, 22 (21-23) for gandotinib (p=0.007). 9/66 pts treated with ruxolitinib (13.6%) and 5/12 with fedratinib (41.7%) had received previous therapy with another JAKi or combined therapy with other molecules. Median duration of treatment was 22 mo (range 1-64) with ruxolitinib, 7 mo (2-18) with fedratinib, 6 mo (4-7) with pacritinib and 4 mo (3-5) with gandotinib. No pts achieved IWG-MRT complete or partial response. Clinical improvement (CI) was achieved by 23/64 evaluable pts with ruxolitinib (35.9%), 3/12 with fedratinib (25%), none with pacritinib and gandotinib. Anemia response (AR) was obtained in 5/26 pts in ruxolitinib (19.2%), 1/6 in fedratinib (16.7%) and none in pacritinib group. Median duration of AR during ruxolitinib was 10 mo, range 5-60. Spleen response (SR) was obtained by 26/64 (40.6%) pts in ruxolitinib, 5/12 (41.7%) in fedratinib, none with pacritinib and gandotinib. Median duration of SR was 13.5 mo (range 4-63) with ruxolitinib and 8 mo (range 4-16) with fedratinib; SR rate with fedratinib might be underestimated due to premature interruption of the trial. Symptoms resolution was achieved by 25/27 pts with ruxolitinib (92.6%), 7/10 with fedratinib (70%) and 0/3 with pacritinib (p=0.0001). 46 patients discontinued JAKi due to adverse events or toxicities (n=17, 37.0%), study closure and inefficacy (n=9 each, 19.6%), disease progression (n=7, 15.2%) and consent withdrawn (n=4, 8.6%). SR was correlated with smaller spleen size at baseline: 63.3% versus (vs) 38.7% for less or more than 50th percentile (16 cm, p=0.03) and 36.7% vs 9.7% for less or more than 75th percentile (22 cm, p=0.007) and with treatment duration: pts who obtained SR had a longer treatment duration (22 mo, range 4-64, vs 14 mo, range 3-62, p=0.028). Pts receiving a previous JAKi vs not pretreated pts had less SR (14 vs 43%, p=0.04) but also had larger SS at enrolment (p=0.021). Conclusions: In this series, CI frequency obtained with ruxolitinib was 35.9% and with fedratinib of 25%, with limitations due to qualitative only symptoms evaluation. SR and AR was obtained with similar frequencies with ruxolitinib and fedratinib. SR is influenced by smaller SS at treatment beginning and by longer treatment duration. Disclosures Vannucchi: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees.
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Bond, T. C., C. Zarzycki, M. G. Flanner, and D. M. Koch. "Quantifying immediate radiative forcing by black carbon and organic matter with the Specific Forcing Pulse." Atmospheric Chemistry and Physics 11, no. 4 (February 16, 2011): 1505–25. http://dx.doi.org/10.5194/acp-11-1505-2011.
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Abstract. Climatic effects of short-lived climate forcers (SLCFs) differ from those of long-lived greenhouse gases, because they occur rapidly after emission and because they depend upon the region of emission. The distinctive temporal and spatial nature of these impacts is not captured by measures that rely on global averages or long time integrations. Here, we propose a simple measure, the Specific Forcing Pulse (SFP), to quantify climate warming or cooling by these pollutants, where we define "immediate" as occurring primarily within the first year after emission. SFP is the amount of energy added to or removed from a receptor region in the Earth-atmosphere system by a chemical species, per mass of emission in a source region. We limit the application of SFP to species that remain in the atmosphere for less than one year. Metrics used in policy discussions, such as total forcing or global warming potential, are easily derived from SFP. However, SFP conveys purely physical information without incurring the policy implications of choosing a time horizon for the global warming potential. Using one model (Community Atmosphere Model, or CAM), we calculate values of SFP for black carbon (BC) and organic matter (OM) emitted from 23 source-region combinations. Global SFP for both atmosphere and cryosphere impacts is divided among receptor latitudes. SFP is usually greater for open-burning emissions than for energy-related (fossil-fuel and biofuel) emissions because of the timing of emission. Global SFP for BC varies by about 45% for energy-related emissions from different regions. This variation would be larger except for compensating effects. When emitted aerosol has larger cryosphere forcing, it often has lower atmosphere forcing because of less deep convection and a shorter atmospheric lifetime. A single model result is insufficient to capture uncertainty. We develop a best estimate and uncertainties for SFP by combining forcing results from 12 additional models. We outline a framework for combining a large number of simple models with a smaller number of enhanced models that have greater complexity. Adjustments for black carbon internal mixing and for regional variability are discussed. Emitting regions with more deep convection have greater model diversity. Our best estimate of global-mean SFP is +1.03 ± 0.52 GJ g−1 for direct atmosphere forcing of black carbon, +1.15 ± 0.53 GJ g−1 for black carbon including direct and cryosphere forcing, and −0.064 (−0.02, −0.13) GJ g−1 for organic matter. These values depend on the region and timing of emission. The lowest OM:BC mass ratio required to produce a neutral effect on top-of-atmosphere direct forcing is 15:1 for any region. Any lower ratio results in positive direct forcing. However, important processes, particularly cloud changes that tend toward cooling, have not been included here. Global-average SFP for energy-related emissions can be converted to a 100-year GWP of about 740 ± 370 for BC without snow forcing, and 830 ± 440 with snow forcing. 100-year GWP for OM is −46 (−18, −92). Best estimates of atmospheric radiative impact (without snow forcing) by black and organic matter are +0.47 ± 0.26 W m−2 and −0.17 (−0.07, −0.35) W m−2 for BC and OM, respectively, assuming total emission rates of 7.4 and 45 Tg yr−1. Anthropogenic forcing is +0.40 ± 0.18 W m−2 and −0.13 (−0.05, −0.25) W m−2 for BC and OM, respectively, assuming anthropogenic emission rates of 6.3 and 32.6 Tg yr−1. Black carbon forcing is only 18% higher than that given by the Intergovernmental Panel on Climate Change (IPCC), although the value presented here includes enhanced absorption due to internal mixing.
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Flouri, I., A. Repa, N. Avgustidis, N. Kougkas, A. Eskitzis, A. Molla Ismail Sali, S. Pitsigavdaki, et al. "POS0580 COMORBIDITY BURDEN IS HIGH IN RHEUMATOID ARTHRITIS AND SPONDYLOARTHRITIS PATIENTS STARTING BIOLOGICS AND PREDICTS THE INCIDENCE OF SERIOUS ADVERSE EVENTS DURING THERAPY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 523.2–523. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3956.
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Background:There is limited information on the burden of comorbidities in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) in real-world clinical practice and its impact on the incidence of serious adverse events (SAE) during biologic disease-modifying anti-rheumatic drug (bDMARD) therapy.Objectives:To evaluate the number of comorbidities in patients with RA and SpA initiating a bDMARD in everyday clinical practice and to explore its association with the occurrence of a SAE during therapy.Methods:Prospective study of all patients who start any bDMARD treatment in a tertiary centre University Hospital. All comorbidities and SAEs (AEs necessitating hospitalization or resulting in significant incapacity/death) are registered by treating physicians. Comorbidities’ number was evaluated using two different indices: total comorbidities count (CC) and Rheumatic Disease Comorbidity Index (RDCI). Statistical analysis was performed using multinomial logistic and Cox regression models.Results:A total of 799 patients were analysed, of which 428 (54%) had ≥3 comorbidities (Table 1). Comorbidity burden was higher in RA, however in multivariable analyses, comorbidities were not significantly associated with diagnosis, but mainly with increasing patient age. Patients received 1701 bDMARD treatments. During a follow-up of 4019 patient-years, 198 patients (RA:134, SpA:64) had a total of 295 SAE (RA: 217, SpA:78).Each one additional comorbidity in CC index was resulting in 16% increased adjusted risk for the first SAE [HR (95%CI) = 1.16 (1.12-1.20), p<0.001], and each additional comorbidity of the RDCI index was resulting in 28% increased risk [HR (95%CI) = 1.28 (1.20-1.37), p<0.001]. Other baseline independent predictors of the first SAE were greater age [HR=1.04, p<0.001] and use of corticosteroids [HR=1.42, p=0.006].Table 1.Biologic treatments and clinical characteristics at baselinePatients, ΝTotalRASpAp799501298Females, Ν (%)535 (67)404 (81)131 (44)<0.001Age, median (IQR) έτη55 (45-65)60 (51-68)46 (36-54)<0.001Disease duration, median (IQR) έτη6.0 (2.5-13)5.4 (3-11)7.4 (2.0-15)<0.001Comorbidities count, median (IQR)3 (1-5)3 (2-6)2 (1-4)<0.001Patients with no comorbidities, Ν (%)103 (13)43 (9)60 (20)<0.001Patients with 1 comorbidity, Ν (%)134 (17)77 (15)57 (19)0.172Patients with 2 comorbidities, Ν (%)134 (17)76 (15)58 (19,5)0.118Patients with ≥3 comorbidities, Ν (%)428 (54)305 (61)123 (41)<0.001RDCI, median (IQR)1 (0-2)2 (0-3)1 (0-2)<0.001Patients with RDCI = 0, Ν (%)267 (33)128 (25.5)139 (47)<0.001Patients with RDCI = 1, Ν (%)185 (23)119 (24)66 (22)0.665Patients with RDCI = 2, Ν (%)163 (20)113 (23)50 (17)0.057Patients with RDCI ≥ 3, Ν (%)184 (23)141 (28)43 (14)<0.001Total bDMARDs initiated by patients, Ν17011098603Co-administered methotrexate, Ν(%)946 (56)674 (61)272 (45)<0.001Co-administered corticosteroids, Ν (%)493 (29)397 (36)96 (16)<0.001DAS28, median (IQR) (in RA and perSpA)5.8 (4.9-6.6)5.8 (5.0-6.6)5.4 (4.2-6.3)<0.001BASDAI, median (IQR) (in axSpA)--5.6 (4.5-7.0)Conclusion:Patients with RA and SpA initiating a bDMARD treatment in real-world clinical practice have a significant comorbidity burden which increases with age and is an independent predictor for an SAE during therapy.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared
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van der Horst-Bruinsma, I., M. Nurmohamed, A. Van Kuijk, S. Siebert, P. Bergmans, K. De Vlam, E. Gremese, et al. "OP0232 FEMALE VERSUS MALE BURDEN OF PSORIATIC ARTHRITIS IS HIGHER AND TREATMENT PERSISTENCE SHORTER AFTER USTEKINUMAB OR TUMOUR NECROSIS FACTOR INHIBITOR TREATMENT: 1-YEAR DATA FROM THE PSABIO STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 142–43. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1575.
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Background:Sex-related differences in biologic treatment of psoriatic arthritis (PsA) have been insufficiently studied in a real-world setting.Objectives:To evaluate impact of sex on PsA, treatment effectiveness and persistence after 1 year of biologic treatment.Methods:PsABio (NCT02627768) is a multinational, prospective real-world study in PsA with ustekinumab (UST) or TNF inhibitor (TNFi) as 1st/2nd/3rd-line biologic. Males and females were compared for disease activity and patient-reported outcomes. Descriptive statistics including 95% CI at baseline (BL) and 12 (±3) months (LOCF) follow-up are presented. Intra-sex comparisons between UST and TNFi cohorts were done by logistic regression analysis, with propensity score adjustment for imbalanced BL covariates and non-response imputation for stopping/switching biologic drugs.Results:Among 494 females and 399 males, age and disease duration were similar. However, differences in disease characteristics at BL were considerable: females had worse scores than males for cDAPSA, HAQ-DI, EQ5D VAS, PsAID-12, pain and comorbidities. At 1 year, similar improvements from BL were observed between sexes, but females remained in a worse health state than males (Table). Achievement of composite endpoints MDA (including VLDA) and cDAPSA LDA (including remission) was high overall (38.6% and 61.5%, respectively), but reached by >2-fold and 3-fold more males than females, respectively. HAQ-DI scores remained worse for females at 1 year (0.95) than for males at BL (0.93). Enthesitis resolution was achieved in 46% of females and 75% of males. No significant differences in effectiveness of UST vs TNFi were detected between sexes (Figure). Kaplan–Meier estimated drug persistence was significantly better in males than females (log-rank p=0.0007). There was no intra-sex difference between UST or TNFi in risk of stopping/switching in males or females.Table 1.Patient and disease characteristics at BL and 1-year by sexBL femaleBL male1-year LOCF female1-year LOCF maleBiologic line, %1st4655N/AN/A2nd34333rd2013Co-treatment, %MTX37.434.3N/AN/ACorticosteroids34.632.1NSAIDs59.964.4Antidepressant7.92.5Comorbidities, %N/AN/ACardiovascular69.059.4metabolic syndrome40.131.7Obesity35.223.7Anxiety/depression12.67.5Smoking status, %N/AN/ANever54.941.9Past16.826.6Current22.724.3Unknown5.77.3Joint counts, nSwollen 666.1 (5.4; 6.9)5.6 (4.7; 6.4)2.2 (1.7; 2.6)1.3 (1.0; 1.6)Tender 6813.2 (12.0; 14.4)10.0 (8.9; 11.1)6.0 (5.2; 6.7)3.6 (2.9; 4.3)cDAPSA score, mean (95% CI)cDAPSA, %32.5 (30.5; 34.4)26.9 (24.9; 29.0)15.9 (14.5; 17.2)10.3 (9.0; 11.6)Remission1.0 (0.3; 2.6)4.0 (2.1; 6.7)17.8 (14.1; 22.0)37.7 (32.4; 43.2)Low6.7 (4.4; 9.7)15.0 (11.3; 19.4)33.0 (28.3; 37.9)36.5 (31.3; 42.0)Moderate38.9 (34.0; 44.0)42.6 (37.2; 48.2)34.3 (29.6; 39.2)16.9 (13.0; 21.4)High53.4 (48.2; 58.4)38.3 (33.0; 43.9)14.9 (11.6; 18.9)8.9 (6.0; 12.5)MDA2.3 (1.0; 4.3)7.7 (5.1; 11.2)27.5 (23.1; 32.1)52.2 (46.6; 57.7)VLDA0.00.9 (0.2; 2.6)6.2 (4.1; 9.0)19.7 (15.6; 24.3)HAQ-DI score1.31 (1.25; 1.37)0.93 (0.86; 1.00)0.95 (0.89; 1.02)0.53 (0.47; 0.59)PsAID-12 score6.1 (5.9; 6.3)5.1 (4.9; 5.3)4.0 (3.8; 4.3)2.7 (2.4; 2.9)EQ5D VAS score48.6 (46.6; 50.5)53.8 (51.6; 55.9)59.2 (56.9; 61.4)68.0 (65.5; 70.4)Enthesitis50.7 (45.9; 55.5)48.1 (42.8; 53.3)32.6 (28.3; 37.3)18.0 (14.1; 22.3)Dactylitis15.6 (12.4; 19.3)24.7 (20.4; 29.3)5.7 (3.8; 8.3)4.8 (2.9; 7.4)Data are % (95% CI) unless indicated otherwise. Bold data are significantly different (non-overlapping 95% CI).Conclusion:These real-world data from PsABio on sex differences with biologic treatment suggest that females generally start biologics in a worse PsA state than males. Although treatment improvements were similar between sexes, females remained in worse health at 1 year, and stopped/switched biologic earlier. More comprehensive treatment before severe disease manifestations evolve may improve management in females.Acknowledgements:This study was funded by JanssenDisclosure of Interests:Irene van der Horst-Bruinsma Consultant of: AbbVie, Lilly, MSD, Novartis, UCB, Grant/research support from: AbbVie, MSD, Pfizer, UCB, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Arno Van Kuijk Consultant of: AbbVie, Janssen, LEO Pharma, Novartis, Grant/research support from: Janssen, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Johnson &Johnson, Novartis Galapagos, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared, Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, MSD, Novartis, Pfizer, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Consultant of: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Wim Noel Employee of: Janssen, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Consultant of: AbbVie, AstraZeneca, Lilly, Novartis, Roche, Laure Gossec Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi
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Oran, Betul, Richard E. Champlin, Jorge E. Cortes, Marcos de Lima, Xuemei Wang, Hsiang-Chun Chen, Farhad Ravandi, Stefan O. Ciurea, Hagop M. Kantarjian, and Gautam Borthakur. "Allogeneic Hematopoietic Stem Cell Transplantation (HCT) in First Remission Improves Outcome Irrespective of FLT3-ITD Allelic Burden Among Patients with Acute Myeloid Leukemia and FLT3-ITD Mutation." Blood 124, no. 21 (December 6, 2014): 2531. http://dx.doi.org/10.1182/blood.v124.21.2531.2531.
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Abstract Presence of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) is associated with poor outcome among patients with cytogenetically normal acute myelogenous leukemia (CN-AML). Patients carrying a higher FLT3-ITD allelic burden have worse outcome. Allogeneic stem cell transplantation (SCT) in first remission (CR1) is reported to improve survival in this poor risk patients. We investigated the impact of FLT3-ITD allelic burden, number of FLT3-ITD mutations and SCT with a matched related or unrelated donor in CR1 in newly diagnosed FLT3-ITD mutated intermediate cytogenetic risk AML patients diagnosed between July 2000 and November 2013, who achieved CR1 with induction therapy. In order to reduce the selection bias, only patients who were alive and free of AML for at least 4 months were included in the analysis (median time to SCT was 4.5 months). The study group had 169 patients and 48 of 169 had SCT in CR1. Patients in the transplant group were younger than those in the non-transplant group (median age 55 v 62 years, p=0.001). As presented in Table1, there was no significant difference in the distribution of gender, white blood cell and platelet counts, bone marrow (BM) blast number, the proportion with CN, the level of FLT3-ITD allele level and number of FLT3-ITD mutations at diagnosis between the two groups. The median follow-up of survivors in the transplant and no transplant groups were similar (30.7 vs. 34.5 months). Overall, SCT in CR1 was associated with longer relapse-free survival (RFS) compared to no-transplant approach. The 3-year RFS from CR1 for transplant patients was 46.3% (95% confidence interval (CI),33.3%-64.2%) compared to 17.5% (95% CI,11.5%-26.4%) for non-transplant patients (P<0.001) (Figure 1). This was largely due to a higher cumulative relapse incidence (RI) of 68% in the non-transplant patients compared to 41% who received SCT (P<0.001). Overall survival (OS) from CR1 was also different between the groups (P=0.0003), with 3-year estimates of 53.5% (95% CI,39.6%-72.3%) for transplant patients compared to 24.3% (95% CI, 17.3%-34.2%) for no-transplant patients. The non-relapse mortality rate of 13% observed with SCT was similar to 15% observed in non-transplant patients (P=0.86). Higher WBC and FLT3-ITD alleleic burden at diagnosis were poor prognostic factors associated with decreased RFS and OS in univariate analyses. Older age decreased OS but not RFS. For multivariate regression, we excluded WBC count at diagnosis from the analysis as high WBC was associated with FLT3-ITD allelic burden at diagnosis. Multivariate regression models showed similar results with SCT in CR1 leading to improved RFS and OS while older age and higher FLT3-ITD allelic burden lost their prognostic significance as shown in Table 2. Our results indicate that SCT in CR1 AML FLT3-ITDmut patients is associated with a longer RFS, largely due to a reduction in the RR. The main reason of treatment failure remains to be relapse and strategies incorporating FLT3-ITD inhibitors before and after SCT may lead to a significant improvement in RFS of this high risk group. Table 1: Patient and disease characteristics All patients Transplant group Non-transplant group p Median age, years (IQR) 59 (50-68) 55 (47-62) 62 (51-70) 0.001 Age <60 85 (50.3%) 30 (62.5%) 55 (45.5%) 0.06 Female 82 (48.5%) 25 (52.1%) 57 (47.1%) 0.6 Diagnosis after 2008 106 (62.7%) 38 (79.2%) 68 (56.2%) 0.01 Median WBC at diagnosis (IQR) 11.6 (3.8-29.7) 9 (3-40) 12 (4-28) 0.98 Median platelets at diagnosis, (IQR) 45 (25-74) 45 (22-84) 45 (25-71) 0.99 Median BM blast count at diagnosis, (IQR) 43(12-74) 32 (6-64) 46 (13-75) 0.2 Diagnostic cytogenetics Diploid 128 (75.7%) 33 (68.8%) 95 (78.5%) Other abnormalities 36 (21.3%) 12 (25%) 24 (19.8%) 0.4 Unknown 5 (2.9%) 3 (6.3%) 2 (0.2%) Median FLT3/ITD allelelic burden, (IQR) 0.34 (0.1-0.47) 0.30 (0.04-0.47) 0.35 (0.12-0.49) 0.3 FLT3/ITD allele ratio <0.3 75 (44.4%) 24 (50%) 51 (42.1%) 0.5 Number of FLT3/ID mutations 1 130 (76.9%) 35 (72.9%) 95 (78.5%) 2 21 (12.4%) 9 (18.8%) 12 (9.9%) 3 12 (7.1%) 3 (6.3%) 9 (7.4%) 0.4 Unknown 6 (3.6%) 1 (2.1%) 5 (4.1%) Table 2: Multivariate regression models for RFS and OS Variables RFS OS HR (95%CI) p HR (95%CI) p Log (FLT3-ITD allele level at diagnosis) 1.12(0.9-1.3) 0.14 1.13 (0.95-1.33) 0.16 HSCT No 1.0 1.0 Yes 0.38 (0.24-0.60) <0.001 0.43 (0.26-0.70) 0.001 Figure 1: Kaplan-Meier estimates of leukemia-free survival by transplant groups Figure 1:. Kaplan-Meier estimates of leukemia-free survival by transplant groups Disclosures Kantarjian: ARIAD, Pfizer, Amgen: Research Funding.
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Hardesty, Brandon M., Stacy Plum, Karen Thibaudeau, Martin Lee, and Amy D. Shapiro. "Pharmacokinetics of Intravenous Infusion of Glu-Plasminogen Concentrate in Patients with Hypoplasminogenemia." Blood 126, no. 23 (December 3, 2015): 3498. http://dx.doi.org/10.1182/blood.v126.23.3498.3498.
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Abstract Background: Hypoplasminogenemia is a rare multisystem disease associated with fibrous deposition on mucous membranes throughout the body, primarily affecting the eyes, ears, sinuses, tracheobronchial tree, genitourinary tract, and gingiva. The best defined clinical manifestation of hypoplasminogenemia is ligneous conjunctivitis, which is characterized by thick, woody (ligneous) growths on the conjunctiva of the eye. Several genetic defects leading to plasminogen deficiency have been identified. Replacement therapy with exogenous plasminogen can achieve resolution of the lesions, but no approved replacement product is available. ProMetic BioTherapeutics, Inc. (ProMetic) is developing a lyophilized human Glu-plasminogen for systemic treatment of hypoplasminogenemia. No pharmacokinetic (PK) data for Glu-plasminogen in plasminogen-deficient patients are available in the literature. However, PK parameters may vary among patients, depending on mutation type or presence of active lesions. The current Phase I dose escalation study is being conducted to provide data on the pharmacokinetic profile and safety of this plasminogen product in patients with hypoplasminogenemia. Methods: Patients with hypoplasminogenemia (plasminogen activity level ≤40% of normal values) received a single IV infusion of 2 mg/kg of plasminogen as the first dosing cohort of a clinical study titled "A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children with Hypoplasminogenemia." The initial dose was chosen based on data generated in the GLP toxicology studies performed with the molecule. The product was supplied in 50 mL vials at a concentration of 6.3 mg/mL, which was reconstituted in 12.5 mL of sterile water for injection. The final concentration of reconstituted plasminogen was 5 mg/mL. Blood samples for PK analysis were taken 30 min prior to dosing, and then at 15 minutes, 1, 6, 24, 48, 72, 96, 120, 168, and 216 hours after infusion. This data is part of a planned analysis after completion of cohort 1 including 5 individuals. Results: Five patients (1 male, 4 females), median age 24 (range 14-38) years received a mean (±SD) volume of 26.6 ± 5.2 ml of plasminogen solution, infused over 10 minutes. Plasminogen activity levels increased from a mean of 34.6 ± 3% to 70.4 ± 7.7% at 15 minutes and slowly decreased to a mean of 45 ± 5.9% at 48 hours (reference range, 70-130%). Plasminogen activity levels for individual patients are shown in Figure 1 below. PK parameters for plasminogen activity through 48 h are shown in Table 1 below. No adverse events considered possibly related to the product were reported following intravenous administration of 2 mg/kg plasminogen. At day 30 no patient exhibited antibodies to plasminogen. Conclusions: ProMetic's lyophilized Glu-plasminogen administered at 2 mg/kg can be given safely to patients with plasminogen deficiency. PK parameters after infusion of 2 mg/kg of plasminogen support moving forward with the next dosing cohort in the clinical trial (6 mg/kg). These data represent the first PK profiles for Glu-plasminogen in plasminogen-deficient patients. The half-life was 27.2 hours, compared with the half-life of 3-4 hours previously reported for Lys-plasminogen in plasminogen-deficient patients. Table 1. PK parameters for plasminogen activity after infusion of 2 mg/kg plasminogen solution in 5 patients with hypoplasminogenemia Geometric mean (95% CI) Half-life (h) 27.2 (16.2-45.7) Cmax (%) 35 (27-46) AUClast (h*%) 935 (683-1280) AUCINF (h*%) 1359 (797-2317) Vz (µg/%/kg)a 57.7 (47.7-69.8) Cl (µg/(h*%)/kg)a 1.47 (0.86-2.51) MRTlast (h) 17.5 (15.0-20.5) MRTINF (h) 38.1 (22.0-65.9) HL, half-life; AUClast, area under the curve up to last measurable concentration; AUCINF, AUC extrapolated to infinity; Vz, volume of distribution; Cl, clearance; MRTlast, mean residence time to the last sampling time; MRTINF, MRT extrapolated to infinity. aPK analysis was performed with plasminogen activity in %; therefore, units cannot be reduced. Figure 1. Plasminogen activity after infusion of 2 mg/kg plasminogen solution in 5 patients with hypoplasminogenemia Figure 1. Plasminogen activity after infusion of 2 mg/kg plasminogen solution in 5 patients with hypoplasminogenemia Disclosures Hardesty: Biogen: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Prometic Biotherapeutics: Research Funding. Plum:ProMetic Biotherapeutics: Employment. Thibaudeau:ProMetic BioTherapeutics: Employment. Lee:ProMetic: Consultancy. Shapiro:ProMetic Life Science, Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octopharma, OPKO, PTC Therapeutics, Selexys: Research Funding; Baxalta, Novo Nordisk, Biogen: Membership on an entity's Board of Directors or advisory committees; Baxalta, Novo Nordisk, Biogen: Consultancy; Biogen: Speakers Bureau.
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Ludwig, Heinz, Elisabeth Rauch, Thomas Kuhr, Adalbert Weissman, Daniel Heintel, Niklas Zojer, Hedwig Kasparu, Richard Greil, and Zdenek Adam. "Significant Activity of Lenalidomide-Dexamethasone in Multiple Myeloma (MM) Patients with Light Chain Induced Acute Renal Failure (LC-ARF)." Blood 120, no. 21 (November 16, 2012): 4031. http://dx.doi.org/10.1182/blood.v120.21.4031.4031.
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Abstract Abstract 4031 Introduction: Excessive production of free light chains with affinity for uromodulin results in protein aggregates and toxic injury of distal renal tubules. The ensuing renal failure is a significant risk factor for infections, dependency on chronic hemodialysis and reduced survival. Management of this emergency includes rapid confirmation of the diagnosis and prompt installment of effective anti-myeloma therapy. Here, we assess the efficacy of lenalidomide-dexamethasone for treatment of patients with LC-ARF. Patients and Methods: 32 patients with LC-ARF as formerly defined (J. Clin. Oncol. 2010 20; 28(30):4635-41) have been enrolled so far. Age (median): 66 years (range: 46–87 years), Gender: male/female: 17/15. All patients presented with ISS stage III. 26 (81.3%) had de novo MM and 6 (18.8%) previously treated, but relapsing disease. Median GFR was 19.9 ml/min (range 6.1 – 37.2 ml/min). ECOG performance status was 0 in 9, I-II in 18 and III-IV in 5 patients, respectively. Lenalidomide was given from d 1–21 with dose adaptation according to GFR as suggested in the prescribing information. Dexamethasone 40 mg was administered on d 1–4, 9–12, 17–20 during cycle 1; thereafter 1x/week. Cycles were repeated q 4 weeks. Results: Presently, 23 patients are evaluable for response (completed ≥2 cycles and fully documented). The median follow-up is 7.7 months, median number of cycles is 9 (range 2–9). CR was achieved in 5 (21.7%), nCR in 1 (4%), VGPR in 2 (8%) and PR in 13 (52%) patients, MR in 1 (3%), respectively, yielding an ORR (CR+nCR+VGPR+PR) of 91.3% for evaluable patients and 65.6% for the ITT population. Median time to first myeloma response was 28 (range 27–63 days) and to best response was 113 days (34–304 days). The cumulative incidence of all patients with myeloma and renal responses are shown in figure 1. Median PFS and OS were 13.8 and 31.2 months respectively in the evaluable patients and 7.4 and 31.2 months in the ITT population. Renal response was assessed as formerly defined (J Clin Oncol. 2010 20; 28(30):4635-41). 4 patients achieved CRrenal, 8 PRrenal and 3 MRrenal, yielding an ORRrenal in 15 patients (65.2% of the evaluable and 46.9% of the ITT population). Median time to first renal response was 28 (range: 27–34) days, and to best renal response 119 days (34–304 days). 5 of 13 dialysis dependent patients became dialysis independent. Median GFR of evaluable patients increased from 15.2 (range 6.1 – 35.1 ml/min) at baseline to a median best GFR of 31.4 ml/min (range 11.3 – 103.2 ml/min). In the 5 patients with CR a significant increase in GFR (median 26.7 to 60.9 ml/min) and in the 16 patients with nCR/VGPR/PR an increase from 13.5 to 30.1 ml/min was observed. Full documentation of adverse events is presently available in 32 patients. 5 patients died within the first 2 months, 2 (8.7%) each due to infection and cardiac arrest and 1 (4.3%) with apoplexia. Grade 3/4 anemia, thrombopenia and leucopenia, were seen in 17 (53.1%), 9 (28.1%), and 5 (15.6%) patients, respectively. Other common grade 3/4 toxicities were infection/sepsis in 13 (40.6%), and cardiac dysfunction in 8 (25%) patients, respectively. Exanthema G3 was seen in 3 patients (9.3%), pulmonary embolism, macula edema and multiple stroke syndrome in 1 (3.1%), potassium deficiency G3/4 in 5 (15.6%), and oral candidiasis in 2 patients (6.3%) each. Conclusions: LD showed significant anti-myeloma activity with an overall myeloma response rate (CR-PR) of 91.3% in the evaluable of 65.5% in the ITT cohort. Renal responses (CRrenal-PRrenal) were observed in 65.2% and 46.9% patients, respectively. Time to first myeloma and first renal response was fast (28 days each). The LD regimen with the lenalidomide dose adjusted to GFR was well tolerated. Updated results will be presented. Disclosures: Ludwig: Janssen Cilag: Honoraria; Mundipharma: Honoraria; Celgene: Honoraria. Off Label Use: Lenalidomide was used of label in combination with dexamethasone in this phase II study in patients with acute light-chain induced renal failure.
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Haferlach, Torsten, Ulrike Bacher, Tamara Alpermann, Wolfgang Kern, Alexander Kohlmann, Susanne Schnittger, and Claudia Haferlach. "Further Insights Into The Molecular Landscape Of De Novo Acute Myeloid Leukemia (AML) Investigating 1,291 Patients." Blood 122, no. 21 (November 15, 2013): 607. http://dx.doi.org/10.1182/blood.v122.21.607.607.
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Abstract Background The Cancer Genome Atlas Research Network (TCGA) published a hallmark sequencing study on molecular mutations in 200 fully characterized adult de novo AML (NEJM 2013). According to their data AML harbor in average 13 mutations in the coding region of the genome of which 5 are in genes known to be recurrently mutated in AML. Further, detailed data on co-occurrence and mutual exclusiveness of molecular mutations was presented. However, given the heterogeneity of AML a cohort of 200 AML might not be fully representative. Aims 1. Compare the published mutation frequency to our cohort 2. Evaluate, whether the mutation frequencies vary with age. 3. Determine the number of additional mutations in genetically defined AML subgroups 4. Analyze the co-occurrence of molecular mutations. Patients and Methods 1,291 adult de novo AML (700 m/591 f; median: 68 yrs; 18-100 yrs) were analyzed for mutations by different PCR assays and next-generation sequencing including the 11 most frequently mutated genes reported by TCGA (FLT3-ITD/-TKD, NPM1, DNMT3A, IDH1, IDH2, TET2, RUNX1, TP53, NRAS, CEPBA, WT1) and also ASXL1, KRAS, MLL-PTD (that had been found at lower frequencies by TCGA), and CBL. Cytogenetics was performed in all cases. Results Mutations were found in NPM1: n=410/1,189 (34.5%), DNMT3A: n=105/340 (30.9%), TET2: n=104/349 (29.8%), FLT3-ITD: n=305/1,231 (24.8%), RUNX1: n=201/1,045 (19.2%), IDH2: n=154/938 (16.4%), ASXL1: n=157/1,000 (15.7%), TP53: n=97/743 (13.1%), NRAS: n=101/842 (12.0%), IDH1: n=93/1,053 (8.8%), FLT3-TKD: n=94/1,132 (8.3%), MLL-PTD: 98/1,181 (8.3%), CEPBA: n=84/1,105 (7.6%) (double-mut: n=38; single-mut: n=46), KRAS: n=38/552 (6.9%), WT1: n=58/918 (6.3%), and CBL: 8/352 (2.3%). These mutation frequencies are comparable to those reported by TCGA. Only ASXL1 mutations were less frequently observed by TCGA (2.5%). The following mutations were more frequent in pts <60 yrs: FLT3-ITD (P=0.003), NPM1mut and WT1mut (P<0.001 for both). In contrast, ASXL1, RUNX1 (P<0.001, each) and TET2mut (P=0.005) were more frequent in pts ≥60yrs. A total of 802 pts were investigated for at least 9 markers (ASXL1, FLT3-ITD, FLT3-TKD, CEBPA, MLL-PTD, IDH1, IDH2, NPM1, RUNX1): The median number of molecular mutations was 2 (range, 0-5; mean±SD, 1.6±0.9). The lowest number of additional mutations was observed in pts with RUNX1-RUNX1T1 (0.3±0.6) and reciprocal MLL rearrangements (mean±SD, 0.4±0.6) followed by CBFB-MYH11 (0.6±0.8), NPM1 (0.9±0.7), CEPBAmut (0.9±1.0), and MLL-PTD (1.2±0.7). In concordance with TCGA results, a significant coincidence of ASXL1mut with IDH2mut and RUNX1mut was found. A total of 335 pts was screened for FLT3-ITD, DNMT3Amut, and NPM1mut in parallel and there was a high coincidence: 27/335 (8.1%) with all 3 mutations and further 63 (18.8%) with 2 out of 3; all combinations P<0.001, each). Beyond the observations within the TCGA study, we found additional positive correlations such as IDH1mut to DNMT3A (P=0.004) and as well to NPM1mut (P=<0.001), and FLT3-ITD to MLL-PTD (P=0.010) as well as to WT1mut (p=0.001). Furthermore, according to the TCGA data, the following mutations were mutually exclusive: TP53mut to NPM1mut and to FLT3-ITD (P<0.001, each), and in addition RUNX1mut to NPM1mut (P<0.001). However, we could not confirm the mutual exclusiveness of RUNX1mut and FLT3-ITD as 21.0% of RUNX1mut AML also showed FLT3-ITD. Beyond the TCGA data, we found the following mutations to show significant negative correlations: MLL translocations were significantly negatively correlated with FLT3-ITD, NPM1, DNMT3A, IDH2, and RUNX1mut, as well were RUNX1-RUNX1T1 rearrangements with FLT3-ITD, NPM1, and IDH2mut, and CBFB-MYH11 rearrangements with FLT3-ITD and NPM1mut. Conclusions 1) Investigation of a large cohort of de novo AML largely confirmed the mutation frequencies of the TCGA data, but revealed a higher frequency of ASXL1mut. 2) In addition, we depicted new patterns of positive and negative correlations of genetic alterations. 3) This further emphasizes the variety of pathways of leukemogenesis in de novo AML requiring additional analyses to delineate the prognostic impact of different marker combinations and their impact on treatment decisions. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Bacher:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
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Farge, Dominique, Philippe Debourdeau, Norbert Claude Gorin, Anne Lamblin, and Francis Cajfinger. "Long-Term Use of Low-Molecular-Weight Heparins (LMWH) for Cancer-Associated Venous Thromboembolism (VTE): Patients’ Perception in Tropique, a Prospective, Multicenter, Observational Study." Blood 124, no. 21 (December 6, 2014): 4272. http://dx.doi.org/10.1182/blood.v124.21.4272.4272.
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Abstract Introduction Long-term treatment with LMWH is the recommended standard for patients with cancer-associated VTE [1, 2]. Data on the long-term prescription of LMWH and treatment follow-up in clinical practice, and particularly the patient’s view on the treatment, are scarce. The main objective of TROPIQUE was to document the prescription and use of LMWH in these patients. A sub-study aimed to assess patients’ perception of long-term anticoagulant treatment with LMWH based on the validated Perception AntiCoagulant Treatment Questionnaire (PACT-Q) [2]. Methods Adult cancer patients with recent symptomatic VTE from the TROPIQUE study were asked to fill-in a PACT-Q at inclusion and at 6 months or study end. PACT-Q1 administered at study start included “Treatment Expectations” (7 items) measured by separate scores expressed on a 5-point Likert scale. PACT-Q2 performed at 6 months or at the end of the study included “Convenience” and “Anticoagulant Treatment Satisfaction” (13 and 7 items, respectively) measured by global scores on a 0-to-100 scale. Results A total of 409 patients (49.9% female), aged 65±12.1 years, were consecutively included from November 2012 to August 2013. Most of cancers were solid tumors; 81% of patients received chemotherapy and 60.9% of cancers were metastatic. Mean treatment duration was 5.28 ± 2.07 months and 98.0% of patients were treated for 3 months or more. PACT-Q1 and PACT-Q2 were collected on a voluntarily basis from 269 (67.8%) and 139 (34.0%) patients, respectively. At study start patients’ treatment expectations were high, particularly regarding the confidence in the treatment to prevent blood clots (mean 3.94 ± 0.75), the expectations of symptom relief (mean 3.98 ± 1.04) and the importance of ease of use (mean 4.22 ± 0.9) while 54.3% of patients had low or no expectations of treatment-related side effects (bruise, bleeding) (mean 2.45±1.1). The treatment was considered convenient (global score 79.7 ± 17.1), with the majority of patients reporting small or no difficulties with taking the treatment (subcutaneous injections) and with regards to impact on daily life. The impact of treatment-related side effects on activities was reported as low. A proportion of 69.1% of patients were overall satisfied or very satisfied with their anticoagulant treatment whereas the experience with treatment-related side effects was worse or much worse than expected for only 12.9% of patients. The “Anticoagulant Treatment Satisfaction” global score was 62.9 ± 16.7. Abstract 4272. Table 1: Cancer patient’s perception of long-term anticoagulant treatment with LMWH [n (%)] Selected perception items* Not at all or to a small extent Moderately Very much or extremely Mean score on Likert scale ± SD PACT-Q1 Treatment expectations (n=269) Confident in preventing clots Symptom relief Side effects (n=267) Importance of ease to use - 10 (3.7) 22 (8.2) 145 (54.3) 17 (6.3) - 45 (16.7) 38 (14.1) 76 (28.5) 14 (5.2) - 214 (79.6) 209 (77.7) 46 (17.2) 238 (88.5) - 3.94 ± 0.75 3.98 ± 1.04 2.45 ± 1.1 4.22 ± 0.9 PACT-Q2 Convenience (n=138) Difficulty in taking treatment (n=137) Difficulties regarding daily life Bother in follow-up required Difficulties on regular intake Side effects impact on activities - 92 (67.2) 101 (73.2) 101 (73.2) 114 (82.6) 116 (84.1) - 37 (27) 26 (18.8) 16 (11.6) 17 (12.3) 14 (10.1) - 8 (5.8) 11 (8.0) 7 (5.1) 7 (5.1) 8 (5.8) 79.7 ± 17.1 Treatment satisfaction (n=137) Experience with side effects (n=132) Worse or much worse 17 (12.9) As expected 55 (41.7) Better or much better 60 (45.5) 62.9 ± 16.7 Overall satisfaction (n=136) Unsatisfied or very unsatisfied 10 (7.4) Neutral 32 (23.5) Satisfied or very satisfied 94 (69.1) *Only some items selected from the PACT questionnaire are shown Conclusion Patients with cancer-associated VTE had high expectations regarding anticoagulant treatment and long-term treatment with LMWH is perceived as convenient with a high degree of patient satisfaction. These results suggest that cancer patient’s capability to accept long-term injectable anticoagulant treatment is probably underestimated. These encouraging observations of patient perception of the anticoagulant therapy are essential in view of improving health professional’s adherence to established treatment recommendations on cancer-associated VTE [3]. 1- Farge D, J Thromb Haemost. 2013 Jan;11(1):56-70. 2- Prins MH, Health Qual Life Outcomes, 2009. 7: p. 9. 3- Debourdeau P, Support Care Cancer. 2008 Dec;16(12):1333-41 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.
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Lyons, Roger M., Billie J. Marek, Carole Paley, Jason Esposito, Katie McNamara, Lawrence Garbo, Nicholas DiBella, and Guillermo Garcia-Manero. "Relationship Between Chelation and Clinical Outcomes in Lower-Risk Patients with Myelodysplastic Syndrome (MDS): Registry Analysis at 5 Years." Blood 124, no. 21 (December 6, 2014): 1350. http://dx.doi.org/10.1182/blood.v124.21.1350.1350.
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Abstract Introduction: We prospectively collected data from lower-risk patients (pts) with MDS in an ongoing US registry in order to assess the association between chelation and clinical outcomes. In addition, we evaluated the association between chelation and overall survival (OS). Here we report outcomes at 5 years. Methods: The registry enrolled 600 pts from 107 US centers. Pts were ≥18 years old with lower-risk MDS (WHO, FAB, and/or IPSS criteria) and transfusional iron overload (serum ferritin ≥1000 µg/L and/or ≥20 packed red blood cell units and/or ≥6 units every 12 weeks). Pts were analyzed by iron chelation status; ie, had never been chelated or had ever used iron chelation, and a subgroup of the latter grouppts with ≥6 mo of chelation. Pts were evaluated every 6 mo for 5 years or until death with respect to characteristics, survival, disease status, comorbidities, cause of death, and MDS therapy. Results: 600 pts (median age, 76 years [range, 21-99], 346 [57.8%] male, 519 [86.6%] Caucasian) were evaluated. IPSS status was similar across chelation groups. Chelated pts (n=271) had a greater median number of lifetime units transfused at the time of enrollment vs nonchelated pts (n=328): 38.5 vs 20.0. At baseline, cardiac and vascular comorbidities (CVC) were significantly higher in nonchelated vs chelated pts (52.4% vs 34.3% [P<0.0001], 59.8% vs 48.0% [P=0.0039], respectively). Endocrine comorbidities (EC) were numerically higher in nonchelated vs ≥6 mo chelated pts (44.2% vs 35.6%). As of May 1, 2014, 61 pts continue in the registry; 538 discontinued (400 died, 66 lost to follow-up, 46 completed study, and 26 discontinued for other reasons). Of the 271 chelated pts, 187 (69.0%) were chelated with deferasirox, 40 (14.8%) with deferasirox and deferoxamine, 32 (11.8%) with deferoxamine, and 1 (0.4%) with an unknown chelator; in 11 (4.1%), the chelator name was not provided. Cumulative duration of chelation was 18.9 mo in pts who had ever used iron chelation and 27.0 mo in pts with ≥6 mo of iron chelation. OS from diagnosis of MDS and time to acute myeloid leukemia (AML) were significantly greater in the chelated vs nonchelated pts (P<0.0001 for both). In pts with CVC, median OS was also significantly greater in chelated vs nonchelated pts (67.66 vs 43.40 mo; P<0.0001). In pts with EC, median OS was also greater in chelated pts (74.98 vs 44.63 mo; P<0.0001) (Table). Patients with ≥6 mo of chelation had numerically fewer deaths in the registry, numerically greater OS, time to death, and time to AML transformation vs pts who had any chelation (Table). Conclusions: Limitations of these analyses include variation in time from diagnosis, duration of chelation, impact of pt clinical status on decision to chelate, and optional conduct of clinical assessments. Nonetheless, the results after 5 years of follow-up of lower-risk pts with MDS suggest iron chelation therapy is associated with improved OS and longer time to AML transformation. Causation has not been established. Abstract 1350. TABLE. Characteristics of Patients Nonchelated, Chelated, and Chelated ≥6 Months Nonchelated n=328 Chelated n=271 Chelated ≥6 Months n=202 Time to death, median (min/max) mo 47.8 (43.4, 53.1) 88.0 (78.4, 103.0) *P<0.0001 100.0 (83.4, 118.2) *P<0.0001 Deaths (n), % 239 (72.9) 161 (59.4) *P=0.0005 115 (56.9) *P=0.0002 Median OS (mo): No CVCMedian OS (mo): With CVC 34.0 (n=42) 43.4 (n=286) 69.3 (n=72) 67.7 (n=199) *P<0.0001 79.3 (n=60) 72.6 (n=142) *P<0.0001 Median OS (mo): No ECMedian OS (mo): With EC 38.5 (n=162) 44.6 (n=166) 67.1 (n=149) 75.0 (n=122) *P<0.0001 69.6 (n=114) 81.8 (n=88) *P<0.0001 Time to AML transformation from diagnosis, median (min, max) mo 46.4 (6.9, 82.5) 72.1 (16.4, 176.6) *P<0.0001 78.8 (16.4, 176.6) *P<0.0001 AML transformation, n (%) 34 (10.4) 17 (6.3) 14 (6.9) Cause of death, n (%) MDS/AML 103 (31.4) 73 (26.9) 53 (26.2) Cardiac 36 (11.0) 21 (7.7) 15 (7.4) Infection 27 (8.2) 14 (5.2) 14 (6.9) Other 16 (4.9) 16 (5.9) 10 (5.0) Unknown 29 (8.8) 18 (6.6) 12 (5.9) Malignancy 14 (4.3) 2 (0.7) 0 (0.0) Respiratory 7 (2.1) 7 (2.6) 4 (2.0) Multiorgan failure 3 (0.9) 3 (1.1) 3 (1.5) CVA 1 (0.3) 5 (1.8) 3 (1.5) GvHD/transplant 3 (0.9) 2 (0.7) 1 (0.5) CVC, cardiovascular comorbidity; EC, endocrine comorbidity; CVA, cerebrovascular accident; GvHD, graft-vs-host disease *Versus nonchelated. Disclosures Paley: Novartis Pharma: Employment. Esposito:Novartis Pharma: Employment. McNamara:Novartis Pharmaceuticals Corporation: Employment. Garcia-Manero:Novartis Pharma: Research Funding.
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Valcárcel, David, Guillermo Sanz, Margarita Ortega, Benet Nomdedeu, Elisa Luño, María Diez-Campelo, M. Teresa Ardanaz, et al. "Identification of Poor Risk Patients in Low and Intermediate-1 (Int-1) IPSS MDS with the New Ipssr Index and Comparison with Other Prognostic Indexes. A Study by the Spanish Group of MDS (GESMD)." Blood 120, no. 21 (November 16, 2012): 702. http://dx.doi.org/10.1182/blood.v120.21.702.702.
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Abstract Abstract 702 Despite that low and intermediate-1 (int-1) IPSS groups are commonly considered as low risk diseases with a median overall survival exceeding 60 months, some of these patients will evolve as higher risk myelodysplastic syndrome (MDS). Recently several new prognosis indexes (PI) have been proposed: The new IPSSr, WPSSr, MD Anderson for lower risk patients (MDA) Index, and the Spanish Group of MDS (GESMD) proposal that considers as high risk those patients with int-1 IPSS and at least one of the following: platelets <30×109/L, granulocytes <0.5×109/L, poor or very poor-risk karyotype or the presence of bone marrow (BM) fibrosis. The aim of the study was to compare the four PI and to analyze which of them was the best to identify patients with the poorest risk (defined as those with a median overall survival (OS) lower than 30 months) and to segregate different risk groups in a population of lower risk MDS patients. Indexes were compared using the Akaike analysis methodology. A total of 2410 patients from the Spanish registry of MDS with low or int-1 IPSS were included. Median age was 74 years (42.6% female). The IPSS value was of: 0, 0.5 and 1 in 1314, 761 and 335 patients, respectively. The four poor risk variables defined by the GESMD confirmed its adverse predictive value for OS: granulocytes <0.5×109/L (n=101, P<0.001), platelets <30×109/L (n=94, P<0.001), poor or very poor risk karyotype (n=35, P=0.007), and BM fibrosis (n=109 of 698 evaluable patients, P<0.001). The presence of at least one of these was associated with adverse prognosis in the int-1 group but not in the low IPSS risk group, thus only the former was considered as high risk. The distribution of patients across the four PI is detailed in the Table. These new PI identified between 16.9% and 46% of patients having a median OS of around 30 months within the int-1 patients (wide line in the table), but none of the PIs could identify such a poor prognosis patients in the low IPSS group. The PI that identified the highest number of patients with shorter OS was the new IPSSr, while MDA IP was the most discriminative in the Akaike analysis. In conclusion, IPSS is not discriminative enough in the int-1 group. In contrast, the application of the new PI can be employed to better identify poor prognosis patients within the int-1 group who could benefit from a high-risk approach. Table. Overall survival and AML evolution according to the different prognostic index. PROGNOSIS INDEX (AIC for the whole population/and for the Int-1) populations) PROGNOSIS GROUP IPSS LOW (N=1314) OS: 87.78 m (95% CI:74.5-101.0) AML EVOLUTION (3 years): 9.1% (95% CI: 6.9-11.3%) IPSS INT-1 (N= 1096) OS: 44.2 m (95% CI:39.1-49.3) AML EVOLUTION (3 years): 26.9% (95% CI: 23-30.8%) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) GESMD (12566.6/6425.9) LOW 1314 (100) 860 (78.5) 48.1 (40.9-55.3)* 25.1 (20.7-29.5)** HIGH 0 (0) 236 (21.5) 32.7 (39.1-49.3)* 34.3 (24.5-44.1)** MD. Anderson (12381.4/6357.2) LOW 508 (39.3) 130.3 (104.6-157.0)* 9% (5.4-12.6)! 109 (9.9) 115.2 (83.8-146.6)* 15.7 (6.5-24.9)* INT 781 (59.4) 69.7 (62.4-77.1)* 8.9% (6.9-11.9)! 653 (59.6) 51.3 (44.2-58.3)* 23.3 (18.3-28.3)* HIGH 25 (1.9) 58.4* (25.4-91.5)* ——–——–— 334 (30.5) 24.1 (19.3-28.9)* 39.9 (31.3-48.5)* IPSS-R (12409.9/6369.6) VERY LOW 690 (52.5) 118.8 (105.7-131.7)* 6.4% (4.2-8.6)*** 79 (7.2) 113.7 (39.9-187.4)* 17.8 (4.6-31)* LOW 602 (45.8) 65.9 (57.6-74.2)* 11.6% (7.8-15.4)*** 505 (46.1) 60.3 (53.3-67.2)* 18.2 (13.4-23)* INT 22 (1.7) 58.9 (25.2-92.7)* 26% (2-50)*** 416 (38) 30.5 (26.1-34.8)* 38.6 (30-47.2)* HIGH 0 (0) 95 (8.7) 21.2 (16.5-25.9)* 48.5 (32.5-64.5)* VERY HIGH 0 (0) 1 (0.1) WPSS-R (12477.4/6414.7) VERY LOW 517 (39.3) 115.2 (103.0-127.4)* 6.5 (3.7-9.3)$ 76 (6.9) 56.5 (38.2-74.9)* 22.8 (10.6-35)* LOW 524 (39.9) 78.5 (66.7-90.3)* 12.1 (7.7-15.5)$ 289 (26.4) 61.3 (48.3-74.2)* 19.2 (12.4-25.6)* INT 61 (4.6) 46.0 (30.8-61.1)* 13.7 (3.1-24.3)$ 386 (5.2) 42.5 (32.8-52.2)* 27.8 (20.8-34.8)* HIGH 3 (0.2) 185 (16.9) 24.11 (19.4-28.8)* 49.3 (35.7-62.9)* VERY HIGH 0 (0) 4 (0.4) NOT EVAL 209 (15.9) 87.8 (74.6-101.3)* 7.2 (3-11.4)$ 156 (14.2) 48 (30.8-65.2) 18.3 (9.1-27.5)* AIC: Akaike Information Criteria. Int: Intermediate, Not Eval: Not evaluable, CI: Confidence interval. * P<0.001; ** P=0.02; *** P=0.04; ! !P=0.7 $P=0.1 Figure. Actuarial curves of overall survival according to the different PI. Figure. Actuarial curves of overall survival according to the different PI. Disclosures: No relevant conflicts of interest to declare.