Journal articles on the topic '346.9 346.9403 23'
To see the other types of publications on this topic, follow the link: 346.9 346.9403 23.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic '346.9 346.9403 23.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Vasilenko, Sara A., Megan K. Maas, and Eva S. Lefkowitz. "“It Felt Good but Weird at the Same Time”." Journal of Adolescent Research 30, no. 5 (December 8, 2014): 586–606. http://dx.doi.org/10.1177/0743558414561298.
Full textAbstract:
Although sexual behavior is multidimensional, little research has focused on the experience of nonintercourse behaviors for adolescents and emerging adults. This article uses open-ended coded data from a longitudinal study of college students ( N = 346; M age = 18.5, 52% female, 27% Hispanic/Latino [HL], 25% non-HL European American, 23% non-HL Asian American, 16% non-HL African American, 9% non-HL multiracial) to examine what emotional responses emerging adults report about their first experiences of six sexual behaviors. The four most common emotional reactions were happy, excited, fearful, and indifferent. Descriptions were largely positive, although mixed reactions were relatively common and emotional reactions varied by behavior. Results suggest the importance of including multiple types of sexual behaviors, as well as their possible positive and negative outcomes, in sexuality education programs.
2
Economidou, Domniki, Spyros Dovas, Aikaterini Papagianni, Panagiotis Pateinakis, and Dimitrios Memmos. "FGF-23 Levels before and after Renal Transplantation." Journal of Transplantation 2009 (2009): 1–5. http://dx.doi.org/10.1155/2009/379082.
Full textAbstract:
Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25VitD levels were measured at the same time periods. Renal threshold phosphate concentration (/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 146 versus 37 9 pg/mL, ) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation.
3
Kuzma-Hunt, Alexander G., Reem Sabry, Ola S. Davis, Vivien B. Truong, Jibran Y. Khokhar, and Laura A. Favetta. "THC and sperm: Impact on fertilization capability, pre-implantation in vitro development and epigenetic modifications." PLOS ONE 19, no. 3 (March 27, 2024): e0298697. http://dx.doi.org/10.1371/journal.pone.0298697.
Full textAbstract:
Global cannabis use has risen 23% since 2010, with 209 million reported users, most of whom are males of reproductive age. Delta-9-tetrahydrocannabinol (THC), the main psychoactive phytocannabinoid in cannabis, disrupts pro-homeostatic functions of the endocannabinoid system (ECS) within the male reproductive system. The ECS is highly involved in regulating morpho-functional and intrinsic sperm features that are required for fertilization and pre-implantation embryo development. Previous work by our group demonstrated that THC altered sperm capacitation and the transcriptome, including several fertility-associated microRNAs (miRs). Despite the prevalent use of cannabis among males of reproductive age, clinical and pre-clinical research investigating the impact of paternal cannabis on sperm function and the outcomes of artificial reproductive technologies (ARTs) remains inconclusive. Therefore, the present study investigates the impact of in vitro THC exposure on morpho-functional and intrinsic sperm functions, including contributions to embryo development following IVF. Bovine sperm were used as a translational model for human and treated with concentrations of THC that reflect plasma levels after therapeutic (0.032μM), and low (0.32μM)-high (4.8μM) recreational cannabis use. After 6-hours of treatment, THC did not alter the acrosomal reaction, but 4.8μM significantly reduced mitochondrial membrane potential (MMP) (p<0.05), primarily through agonistic interactions with CB-receptors. Fertilization of bovine oocytes with THC-treated sperm did not alter developmental rates, but blastocysts generated from sperm treated with 0.32–4.8μM THC had fewer trophoblasts (p<0.05), while blastocysts generated from sperm exposed to any concentration of THC had fewer cells in the inner cell mass (ICM), particularly within the 0.032μM group (p<0.001). Fertility associated miRs, including miR-346, miR-324, miR-33b, and miR-34c were analyzed in THC-exposed sperm and associated blastocysts generated by IVF, with lower levels of miRs-346, -324, and -33b found in sperm treated with 0.32μM THC, while miR-34c levels were higher in sperm treated with 0.032μM THC (p<0.05). Levels of miR-346 were also lower in sperm treated with 0.032μM THC, but higher in blastocysts generated from sperm exposed to 0.32μM THC (p<0.05). Our findings suggest that THC may alter key morpho-functional and epigenetic sperm factors involved in fertilization and embryo development. This is the first study to demonstrate that sperm exposed to THC in vitro negatively affects embryo quality following IVF.
4
Zampatti, N., A. Garaiman, S. Jordan, M. O. Becker, B. Maurer, R. Dobrota, O. Distler, and C. Mihai. "FRI0267 CLINICAL CORRELATES AND RELEVANCE OF UCLA GIT 2.0 FOR ESOPHAGITIS AND INDICATION FOR ESOPHAGOGASTRODUODENOSCOPY IN REAL-LIFE PATIENTS WITH SYSTEMIC SCLEROSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 718.1–718. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4291.
Full textAbstract:
Background:The gastrointestinal (GI) tract is frequently involved in systemic sclerosis (SSc). The University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) is validated to capture GI morbidity in patients with SSc (1). The routine clinical investigation of GI involvement in these patients is not standardized and there is no consensus about when and how frequently an esophagogastroduodenoscopy (EGD) should be performed.Objectives:The main aim of this study was to analyze the capacity of UCLA GIT 2.0 to identify patients with erosive esophagitis in an unselected, real-life SSc patients’ cohort. Secondary aim was to determine whether the UCLA GIT 2.0 could discriminate SSc patients for whom an expert rheumatologist would recommend an EGD.Methods:We selected patients fulfilling the ACR/EULAR 2013 criteria for SSc from the Zurich cohort, having completed at least once the UCLA GIT 2.0 questionnaire. We reviewed the medical charts of SSc patients from 2013 to 2019 and recorded data on EGD. We analyzed by univariable logistic regression several parameters, including UCLA GIT 2.0, considered as potentially associated with 1) the referral to EGD and 2) macroscopic esophagitis according to the Los Angeles criteria.Results:We identified 346 patients (82.7% female, median age 63 years, median disease duration 10 years, 23% with diffuse cutaneous SSc) satisfying the inclusion criteria, who filled in 940 UCLA GIT 2.0 questionnaires.From 940 visits, 31 were excluded because EGD was done within 3 months before completing the UCLA GIT 2.0. In the 909 remaining visits, EGD was recommended by the expert rheumatologists in 128 cases. In logistic regression, UCLA GIT 2.0 total score and some of its subscales, but also the modified Rodnan skin score (mRSS) and esophageal and stomach symptoms by past medical history, associated with the referral to EGD (Table 1).Table 1.Logistic regression of factors associated with referral to EGDOR (95% CI)p-valuemRSS1.04 (1.01 - 1.06)0.009Hemoglobin (Hb)1.00 (0.96 - 1.04)0.978Proton pump inhibitor (PPI)0.37 (0.12 - 1.15)0.086Esophageal symptoms3.37 (2.28 - 4.96)<0.001Stomach symptoms2.93 (2.02 - 4.26)<0.001Reflux subscale2.04 (1.52 - 2.73)<0.001Distention/bloating subscale1.53 (1.24 - 1.89)<0.001Social functioning2.20 (1.57 - 3.07)<0.001Emotional wellbeing1.42 (1.03 - 1.97)0.034Total score of UCLA GIT 2.02.27 (1.55 - 3.32)<0.001We found data on 177 EGD performed in 150 patients, meaning that 49 EGD were performed on indication by another physician. In logistic regression, mRSS and esophageal symptoms correlated with esophagitis, while neither the total ULCA GIT 2.0 score nor the reflux subscale or any of the other subscales showed an association with esophagitis (Table 2).Table 2.Logistic regression of factors associated with esophagitisOR (95% CI)p-valuemRSS1.09 (1.03 - 1.15)0.001Hb1.03 (0.99 - 1.06)0.126PPI0.52 (0.27 - 1.03)0.059Esophageal symptoms2.92 (1.29 - 6.61)0.010Stomach symptoms1.60 (0.80 - 3.21)0.183Reflux subscale1.07 (0.60 - 1.93)0.816Distention/Bloating subscale0.63 (0.39 - 1.01)0.054Social functioning0.65 (0.31 - 1.35)0.245Emotional wellbeing0.77 (0.36 - 1.61)0.483Total score of UCLA GIT 2.00.67 (0.28 - 1.60)0.367Conclusion:In a real-life setting, UCLA GIT 2.0 subscales (reflux, distention/bloating, social functioning, emotional wellbeing) and total score strongly associated with expert interpretation of gastroesophageal symptoms and consecutive referral to EGD. However, they showed no correlation with esophagitis on EGD. The main clinical association of esophagitis was the presence of esophageal symptoms.References:[1]Khanna D, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009;61(9):1257-63.Disclosure of Interests:Norina Zampatti: None declared, Alexandru Garaiman: None declared, Suzana Jordan: None declared, Mike O. Becker: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Rucsandra Dobrota: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Carina Mihai: None declared
5
Niesvizky, R., A. Spencer, M. Wang, D. Weber, C. Chen, M. A. Dimopoulos, Z. Yu, et al. "Increased risk of thrombosis with lenalidomide in combination with dexamethasone and erythropoietin." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7506. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7506.
Full textAbstract:
7506 Background: Lenalidomide (Len) is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against multiple myeloma (MM) and additive effects when combined with dexamethasone (Dex). At the interim analysis of MM-009/010, lenalidomide/dexamethasone achieved a significant benefit over dexamethasone, providing a longer median time to progression (TTP), higher response rates, and higher CR rates. Aim: This subgroup analysis of MM-009/010 was performed to evaluate thrombosis in patients receiving Len/Dex vs Dex. Thrombotic events included the following adverse event terms: thrombosis, deep venous thrombosis, thromboembolism, and pulmonary embolism. Methods: Patients (pts) with relapsed or refractory MM were randomized to either receive oral Len (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on Days 1–4, 9–12, 17–20 every 4 weeks for 4 months, then 40 mg on Days 1–4 every cycle thereafter) or placebo plus Dex. Results: Thrombotic events were reported in 39 (11.3%) of 346 pts treated with Len/Dex compared to 13 (3.8%) of 346 pts treated with Dex alone (p < 0.001). Multivariate analysis identified Len/Dex treatment and erythropoietic treatment to be independently correlated with thrombosis (Table). Older age, lower plasma cell percentage in marrow, and better ECOG performance status had a weaker association with thrombosis. Thrombosis occurred more frequently among pts with prior history of thrombosis, although that was not a significant predictor in the multivariate anlaysis. None of 23 pts who used aspirin or salicylate during the first month of treatment developed thrombosis and all events occurred in pts with rising M-paraprotein levels at baseline. Conclusions: The current study findings suggest that the administration of erythropoietic agents should be minimized in MM pts receiving Len/Dex. Prophylactic antithrombotic therapy should also be considered. [Table: see text] [Table: see text]
6
Deters, Erin L., and Stephanie L. Hansen. "346 Effect of supplemental vitamin E in feedlot receiving diets on steer performance and immune function." Journal of Animal Science 97, Supplement_2 (July 2019): 141. http://dx.doi.org/10.1093/jas/skz122.250.
Full textAbstract:
Abstract Single-source, Angus-cross steers (n = 204; 249 ± 23 kg) were utilized to determine the effect of supplemental vitamin (VE; ROVIMIX E-50 Adsorbate, DSM Nutritional Products) on performance and immunity during feedlot receiving. Seven days post-arrival, steers were blocked by BW and weaning protocol (pre-weaned or not) into pens (n = 5 or 6 steers/pen) and pens randomly assigned to VE treatments: no supplemental VE (CON), VE at 25 IU/kg DM (LOW; average 151 IU·steer-1·d-1), 500 IU·steer-1·d-1 (MED), or 1000 IU·steer-1·d-1 (HIGH). Steers were weighed on d -1, 0, 14, 26 and 27. On d 6, steers were boostered with Bovi-Shield Gold (One Shot, Zoetis). Serum collected from one steer per pen was analyzed for Se and α-tocopherol (d -1 and 26) and Bovine Viral Diarrhea Virus (BVDV) type 1 and 2 antibody titers (d 6, 14, 26). Data were analyzed using Proc Mixed of SAS with pen as the experimental unit (n = 9 pens/treatment), the fixed effects of treatment and block, and the random effect of pen. Linear, quadratic and cubic contrast statements were constructed. Serum Se and α-tocopherol concentrations from d -1 and titers from d 6 (prior to vaccination) served as covariates. From d 14 to 27, ADG and G:F quadratically increased (P ≤ 0.02), with MED being greatest; VE did not affect d 0 to 14 or overall trial performance (P ≥ 0.14). Day 26 BVDV type 1 antibody titers and α-tocopherol concentrations (2.7, 3.4, 4.6, and 5.8 mg/L for CON, LOW, MED, and HIGH, respectively) linearly increased due to VE (P ≤ 0.04). Increasing supplemental VE improved circulating VE concentrations and antibody response to a booster vaccine. Performance benefits were observed when VE was supplemented at 500 IU·steer-1·d-1, the dose recommended by NASEM (2016) for stressed cattle.
7
Rijal, Tirtha Raj, Govinda Bahadur Hamal, Purushhotam Jha, and Keshab Babu Koirala. "Identification of Resistant Genotypes on Rice against Blast Disease under Field Condition at Rampur, Chitwan." International Journal of Applied Sciences and Biotechnology 5, no. 4 (December 24, 2017): 505–10. http://dx.doi.org/10.3126/ijasbt.v5i4.18773.
Full textAbstract:
Blast disease is considered as a major limiting factor in the global rice production because of its wide distribution and destructiveness and it has been causing significant yield loss in all rice growing areas of Nepal. Host resistance is the most desirable means of managing blast, especially in developing countries. Considering the importance of this disease field screening experiment was conducted to identify resistant rice genotypes against this disease. A total of 314 and 346 rice genotypes with resistant (Sabitri) and susceptible checks (Sankarika) were evaluated under epyphytotic conditions during 2016 and 2017 summer seasons at Rampur, respectively. During 2016 disease severity varied from 1 to 9 and only five genotypes; Sabitri, IR 12L 110, WAS122-IDSA14-WASB-FKRI, IR 10F 559and IR 10F 616 were resistant, 30 moderately resistant, 150 susceptible and 129 highly susceptible against blast disease. Similarly during 2016 out of 346 genotypes, 23 resistant as ARIZE SWIFT GOLD, IR95784-21-1-1-2, NR2169-10-4-1-1-1-1-1-2, NR2169-10-2-3-1-1-1-1-1, NR2181-165-1-1-1-1-1-1-1, NR2167-48-5-1-2-1-1, NR2171-2-1-1-3-1-1-2, NR2170-5-5-1-6-1-1-3-1, NR2170-31-1-1-5-1-1-1-1, NR2167-41-1-1-3-1, NR2172-34-1-1-1-1-1-1-1, Sabitri, IR82589-B-B-114-3, IR79913-B-238-3-3, IR93823-36, IR08L 152, IR82589-B-B-51-4, IR09F 434, IR55423-01, IR94391-131-353-19-B-1-1-1-1-1, NR2154-8-1-1-1-1-1, NR 2124-43-3-1-1-1, NR2160-68-1-1-1-1-1., 72 moderately resistant, 191 susceptible and 155 were highly susceptible. Most of the highly susceptible genotypes were knocked down at the time of disease scoring.Int. J. Appl. Sci. Biotechnol. Vol 5(4): 505-510
8
Bower, H., T. Frisell, D. DI Giuseppe, B. Delcoigne, and J. Askling. "OP0133 DO JAKIS WORK THE BEST AMONG THOSE RA PATIENTS WHERE THEIR SAFETY CONCERNS ARE THE HIGHEST?" Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 88.1–88. http://dx.doi.org/10.1136/annrheumdis-2023-eular.346.
Full textAbstract:
BackgroundSafety is a driving factor when selecting treatment, but the risks should be balanced against the treatment benefits, relative to alternative treatment options. In JAKis, recent evidence of increased safety risks in older patients with cardiovascular (CV) risk factors, have led to concerns. However, an increased risk among certain patients might still be offset by an increasing benefit in the same patient segment, and vice versa. A full understanding of the JAKi benefit-risk profile thus requires a better understanding of the relative (JAKi vs other treatments) benefits in those patients where their relative safety profile may be worse.ObjectivesTo assess the observed and adjusted relative effectiveness (remission and response) of JAKis (and non-TNFi bDMARDs) when compared to TNFi, as used in clinical practice, and to assess whether the predicted effectiveness of either drug class is modified by age and the presence of CV risk factors.MethodsRA patients initiating treatment with a JAKi, non-TNFi, or TNFi 2016-2021 were followed using the Swedish Rheumatology Quality Register. Good EULAR response and remission (CDAI<=2.8) at 6 months were assessed at return visits (within 90 to 270 days after treatment initiation). Non-responder imputation was implemented where treatment ended prior to 210 days after initiation.Crude probabilities of outcomes were presented by age and having ≥1 CV risk factor (Y/N). Linear regression estimated the risk difference (versus TNFi) in age and CV risk groups, adjusted for sex, baseline DAS28 (response) and CDAI (remission), and line of therapy. Probability of outcome was predicted from logistic regression models, fitted to allow effect modification of treatment cohort by age and CV risk score (ERS-RA score), adjusted for sex, baseline DAS28 (response) and CDAI (remission), and line of therapy.Results10,309 treatment episodes contributed data on response at 6 months, and 12,016 episodes with data on remission. Overall, 21% achieved good EULAR response and 11% reached CDAI remission (Table 1).Crude observed risks overall indicated superior response and remission with TNFi versus JAKi (Table 1). Adjusted risk differences suggested superior outcomes in JAKi versus TNFi, overall, and in those with no CV risk for CDAI remission. Patterns of predicted response and remission varied across age and CV ERS-RA score (Figure 1), with JAKis having superior effectiveness overall once adjusting for line of therapy.ConclusionAge and CV risk may modify the absolute and relative effectiveness of JAKis vs. TNFi. Further analyses are planned with the aim of presenting these results at EULAR.Table 1.Observed crude proportions of patients who achieved response and remission, and adjusted* risk differences between JAKi, non-TNFi and TNFi using the latter as referenceProportion (N) achieving outcomeAdjusted* risk difference, versus TNFi (95%CI)JAKiNon-TNFiTNFiJAKiNon-TNFiGood EULAR responseN Treatments101220224032Overall20% (339)19% (595)24% (1490)4.0% (1.1, 7.0)2.2% (-0.1, 4.5)<65 years, no CV21% (142)23% (277)27% (803)3.5% (-0.3, 7.3)2.4% (-0.6, 5.5)<65 years, ≥1 CV32% (24)29% (35)26% (60)14.6% (1.3, 28.0)10.7% (-0.1, 21.5)≥65 years, no CV25% (83)24% (168)30% (352)4.3% (-1.4, 10.1)-0.0% (-4.3, 4.3)≥65 years, ≥1 CV23% (29)29% (64)29% (89)1.4% (-8.4, 11.1)3.3% (-4.9, 11.5)CDAI remissionN Treatments139927565533Overall11% (73)9% (114)15% (425)4.0% (2.3, 6.8)2.2% (0.1, 3.6)<65 years, no CV6% (4)5% (6)12% (26)5.0% (2.0, 8.1)2.7% (0.3, 5.0)<65 years, ≥1 CV13% (40)10% (64)14% (159)-1.8% (-9.3, 5.8)-2.9% (-8.7, 3.0)≥65 years, no CV10% (12)12% (26)8% (23)5.7% (1.0, 10.5)0.4% (-3.0, 3.9)≥65 years, ≥1 CV11% (73)9% (114)15% (425)6.9% (-0.2, 14.0)6.9% (0.9, 13.0)*adjusted for sex, baseline DAS28 (response) and CDAI (remission), line of therapy≥1 CV= more than one CV risk factorFigure 1.Predicted probability of response and remission at 6 months by age and CV risk of patients with RA treated with JAKi, non-TNFi and TNFi in Sweden, adjusted for sex, baseline DAS28 (response) and CDAI (remission), and line of therapyREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
9
Fein, L. E., A. Romera, C. M. Micheri, M. I. Diaz, and R. A. Sala. "Identification of the causes that influence recruitment in oncology clinical trials (OCT)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e17562-e17562. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e17562.
Full textAbstract:
e17562 Background: Prediction of patient recruitment in OCT is one of the most important variables to guarantee timely closure of the trial. Earlier data analysis and conclusions define further research or discontinuation of the development of a given drug. Methods: Retrospective analysis of the recruitment and clinical records of all the patients of the COR that were contacted to participate in an OCT from 2006 to 2008 to identify the causes according to which patients did not participate. Results: Total of candidates 346, 175 women (50.6%). Average age 60 years (range 36 to 89). 42 patients (12%) rejected to participate in an OCT. 80 patients (23%) were screening failures (SF). 59 patients (17%) for not fulfilling an inclusion criteria (IC). Non appropriate stage or absence of measurable disease at screening (35%), abnormal labs (14%) and state of receptors or biomarkers (9%). Total of clinically unpredictable IC SF was 57.5%. 21 patients (6%) were SF due to an exclusion criteria (EC). Presence of distant metastases (12,5%), abnormal labs (2.5%) and abnormal EKG (2.5%). Total of clinically unpredictable EC SF was 19%. Conclusions: 35% of candidate patients did not participate. The most frequent cause was SF (23%). 76.5% of these SF were impossible to determine when informed consent was signed. 12% of patients rejected to participate for different reasons. Our results did not identify a predominant modifiable reason to improve recruitment. For future feasibility analyses our estimation of 35% dropout will be considered standard. [Table: see text] No significant financial relationships to disclose.
10
Arigliani, Michele, Sean Zheng, Gary Ruiz, Subarna Chakravorty, Cara J. Bossley, David Rees, and Atul Gupta. "Comparison of pulse oximetry and earlobe blood gas with CO-oximetry in children with sickle cell disease: a retrospective review." BMJ Paediatrics Open 4, no. 1 (June 2020): e000690. http://dx.doi.org/10.1136/bmjpo-2020-000690.
Full textAbstract:
ObjectivesTo investigate the agreement between pulse oximetry (SpO2) and oxygen saturation (SaO2) measured by CO-oximetry on arterialised earlobe blood gas (EBG) in children and adolescents with sickle cell disease (SCD).Design and settingWe retrospectively reviewed 39 simultaneous and paired SaO2 EBG and SpO2 measurements from 33 ambulatory patients with SCD (32 subjects with Haemoglobin SS and one with Haemoglobin Sß+, 52% male, mean±SD age 11.0±3.6, age range 5–18). Measurements were performed between 2012 and 2015 when participants were asymptomatic. Hypoxaemia was defined as SaO2 ≤93%. A Bland-Altman analysis was performed to assess the accuracy of SpO2 as compared with EBG SaO2.ResultsThe mean±SD SpO2 and SaO2 values in the same patients were, respectively, 93.6%±3.7% and 94.3%±2.9%. The bias SpO2–SaO2 was −0.7% (95% limits of agreement from −5.4% to 4.1%) and precision was 2.5%. In 9/39 (23%) cases, the difference in SpO2–SaO2 was greater than the expected error range ±2%, with SaO2 more often underestimated by SpO2 (6/9), especially at SpO2values ≤93%. Thirteen participants (33%) were hypoxaemic. The sensitivity of SpO2 for hypoxaemia was 100%, specificity 85% and positive predictive value 76%.ConclusionsPulse oximetry was inaccurate in almost a quarter of measurements in ambulatory paediatric patients with SCD, especially at SpO2values ≤93%. In these cases, oxygen saturation can be confirmed through EBG CO-oximetry, which is easier to perform and less painful than traditional arterial blood sampling.
11
Silvestro, Lucrezia, Ferdinando De Vita, Arndt Vogel, Thomas Jens Ettrich, Eric Van Cutsem, Maria Di Bartolomeo, Yulia D'yachkova, et al. "Safety of ramucirumab in patients with advanced gastric cancer in Europe and North America: A prospective observational registry." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 341. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.341.
Full textAbstract:
341 Background: The objective was to describe the safety of ramucirumab (Ram) for previously treated advanced gastric cancer under real-world conditions in Europe and North America. Methods: This was a non-interventional, descriptive study of adult patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed after first-line chemotherapy (I4T-MC-JVDD). Data collection began in December 2015 and was completed in August 2021. Patients were followed up to 12 months after initiation of Ram. Safety outcomes included adverse events (AEs)/serious AEs (SAEs), and AEs leading to dose adjustment or death. Subgroups of interest were elderly, patients with cardiac comorbidities, hepatic, or renal impairment. Results: 606 patients were classified in 3 cohorts: Ram monotherapy (Ram Mono, N=51); Ram plus paclitaxel (Ram+PTX, N=547); or Ram plus other anti-cancer agents (N=8). Most patients were male (70%), white (97%) and aged ≥65 (55%); 22% of the population was ≥75 years old. Metastatic cancer was reported in 552 patients (96%); primary tumor location was gastric in 417 patients (69%) and in the gastroesophageal junction in 189 patients (31%). Patients were previously treated mainly with platinum (97%) and fluoropyrimidine (96%). Hypertension was the most frequently reported historical medical condition (25%). At baseline, 23% patients had documented cardiac comorbidities, 11% hepatic impairment and 6% renal impairment. The median duration of Ram was 8 weeks (IQR=4.0-10.6) in Ram Mono and 15 weeks (IQR=8.4-26.7) in Ram+PTX. Regardless of causality, 98% of patients experienced ≥1 AE; most commonly fatigue (31%) and abdominal pain (20%) in Ram Mono cohort; and fatigue (46%) and neuropathy (31%) in Ram+PTX cohort. In total, 40% experienced ≥1 AE of special interest; most commonly bleeding/hemorrhage (21% [mainly epistaxis]) and hypertension (11%). In total, 33 patients (5%) died due to AEs that occurred on, or within 90 days of last dose of Ram, 9 (2%) were related to Ram treatment as per physician’s assessment. Conclusions: The observed safety profile of Ram in the real-world setting was manageable and consistent with the established safety profile of Ram identified from clinical trials. No new safety concerns or notable findings were observed overall or in the subgroups of interest. Clinical trial information: ENCEPP/SDPP/9400 . [Table: see text]
12
Higuchi, T., K. Honda, T. Fukuoka, H. Negoro, and K. Wakabayashi. "Release of oxytocin during suckling and parturition in the rat." Journal of Endocrinology 105, no. 3 (June 1985): 339–46. http://dx.doi.org/10.1677/joe.0.1050339.
Full textAbstract:
ABSTRACT A highly sensitive and specific radioimmunoassay (RIA) for oxytocin was developed and used to measure oxytocin concentrations during both suckling and parturition in individual rats. In urethane-anaesthetized rats, the suckling stimuli, provided by ten pups, induced intermittent increases in intramammary pressure of about 10 mmHg. This was associated with a significant (P < 0·01) increase in serum oxytocin levels from 19·5 ± 4·5 (s.e.m., n = 9) to 49·1 ± 7·4 pmol/l (n = 9) in the samples taken within 30 s from the time of the peak in the pressure. These rises in serum oxytocin returned rapidly to the basal levels as expected from the short half-life (1·46 min) of oxytocin in general circulation. On day 22 or 23 of gestation, serum oxytocin levels remained stable until 0–0·5 h before the first fetus was expelled. They then increased significantly (P < 0·01) from 27·6± 4·6 pmol/l (n = 19) in samples taken 0–0·5 h before to 45·1 ± 5·6 pmol/l in samples taken after the expulsion of the first fetus and gradually increased until the last fetus was expelled. Serum oxytocin concentrations then declined but remained higher than those observed before the first fetus had been born until at least 1–1·5 h after the expulsion of the last fetus. Thus, this oxytocin RIA revealed increased concentrations of the hormone in blood during both suckling and parturition in the rat. J. Endocr. (1985) 105, 339–346
13
Kiladjian, Jean-Jacques, Claire Harrison, Ruben A. Mesa, Haifa K. Al-Ali, John Mascarenhas, Fabian Sanabria, Julie Vienne Bürki, Bourras-Rezki Bengoudifa, and Francesco Passamonti. "POSTER: MPN-346 INDEPENDENCE: Enrolling Phase III Trial to Study the Efficacy and Safety of Luspatercept versus Placebo in Patients With Myelofibrosis on JAK2 Inhibitor (JAK2i) Therapy Requiring Red Blood Cell Transfusions (RBCTs)." Clinical Lymphoma Myeloma and Leukemia 23 (September 2023): S192. http://dx.doi.org/10.1016/s2152-2650(23)00655-9.
Full text
14
Cox, B. E., C. R. Rosenfeld, J. E. Kalinyak, R. R. Magness, and P. W. Shaul. "Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy." American Journal of Physiology-Heart and Circulatory Physiology 271, no. 1 (July 1, 1996): H212—H221. http://dx.doi.org/10.1152/ajpheart.1996.271.1.h212.
Full textAbstract:
Uteroplacentral responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANG II receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1, Ile8]ANG II (AT1 and AT2), losartan (AT1) PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANG II (0.05 microM) increased PGI2 synthesis 62%, from 214 +/- 13 to 346 +/- 23 pg.mg-1.h-1 (P < 0.05). Losartan (1.0 microM) inhibited the rise in PGI2 (257 +/- 24 vs. 238 +/- 25 pg.mg-1.h-1), whereas 1.0 microM PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg.mg-1.h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UASM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.
15
Freetly, H. C., and C. L. Ferrell. "Net uptakes of oestradiol-17β and progesterone across the portal-drained viscera and the liver of ewes." Journal of Endocrinology 141, no. 2 (May 1994): 353–58. http://dx.doi.org/10.1677/joe.0.1410353.
Full textAbstract:
Abstract The objective of this study was to determine whether circulating concentrations or prior exposure to oestradiol-17β (OE2) and progesterone affected their uptake by splanchnic tissues. Catheters were surgically placed in the portal vein, a branch of the hepatic vein, a mesenteric vein and the abdominal aorta of three multiparous ovariectomized Dorset ewes. Blood and plasma flow across the portal-drained viscera (PDV) and the liver, and net uptake of OE2 and O2 consumption in these same tissues were determined in ovariectomized ewes (control), during OE2 infusion into the jugular vein, 7 days after an OE2 implant had been given, and during OE2 infusion into the jugular vein 7 days after an OE2 implant. The above treatments were repeated for progesterone. Plasma flows across visceral organs were determined by marker dilution (para-aminohippuric acid), and OE2 and progesterone concentrations were determined by radioimmunoassay. During the infusion with OE2, OE2 arterial concentration (mean ± s.d.) was 346 ± 199 pg/ml, PDV net uptake was 9·7±5·6 μg OE2/h and hepatic net uptake was 15·5 ± 9·5 μg OE2/h. Hepatic uptake was 82% of the jugular OE2 infusion rate. Blood flow and oxygen consumption by hepatic tissue increased when ewes were exposed to an OE2 implant for 7 days. During the infusion with progesterone, progesterone arterial concentration (mean ± s.d.) was 8·8 ±3·4 ng/ml, PDV net uptake was 220 ± 118 μg progesterone/h and hepatic net uptake was 238 ± 52 μg progesterone/h. Hepatic net uptake was 23% of the progesterone jugular infusion rate. Journal of Endocrinology (1994) 141, 353–358
16
Jnyah, MK, I. El Mezouar, N. Akasbi, and T. Harzy. "Is Hypovitaminosis D Associated with Increased Pain in Patients with Knee Osteoarthritis?" SAS Journal of Medicine 10, no. 07 (July 3, 2024): 612–16. http://dx.doi.org/10.36347/sasjm.2024.v10i07.005.
Full textAbstract:
Objective: Osteoarthritis is considered the most frequent joint pathology mostly interesting the knee. Hypovitaminosis D, frequent during postmenopausal period, is usually found during osteoarthritis. The aim of this study was to investigate a possible association between hypovitaminosis D in patients followed for knee osteoartritis and an increase in pain. Material and Methods: This is a retrospective descriptive and analytical study including 228 patients followed up for knee osteoarthritis in rheumatology consultation between January 2021 and February 2023. Patients who received vitamin D supplementation were excluded. Results: Of 385 patients with knee osteoarthritis, 228 had a vitamin D dosage and were subject of our study. The average age was 60.15+/-11.17 years. 205 of these patients were women (91%) and 23 were men (9%). The mean duration of progression of knee osteoarthritis was 5.61+/-3.6 years. Vitamin D deficiency (<30ng/L) was observed in 89.5% and only 10,5% had normal vitamin D levels. 94.3% were on analgesic treatment and 54.2% on non-steroidal anti-inflammatory drugs. In univariate analysis, a low vitamin D level was strongly associated with painful knee osteoarthritis with the use of anti-inflammatory drugs and conventional analgesics with an Odds Ratio and a p respectively at OR=2.774(1.05-7.27) - p=0.03 and OR=3.44 (1.41-8.39) - p=0.004. Conclusion: According to our study, the association of hypovitaminosis D and knee osteoarthritis could be responsible of an increase in pain in our patients explaining an increased use of analgesics and anti-inflammatory drugs (NSAID).
17
Schwarz, Viktoria, Felix Mahfoud, Lucas Lauder, Wolfgang Reith, Stefanie Behnke, Sigrun Smola, Jürgen Rissland, et al. "Decline of emergency admissions for cardiovascular and cerebrovascular events after the outbreak of COVID-19." Clinical Research in Cardiology 109, no. 12 (August 4, 2020): 1500–1506. http://dx.doi.org/10.1007/s00392-020-01688-9.
Full textAbstract:
Abstract Background The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2. Methods We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1–9, 2020) and after (calendar weeks 10–16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year. Results In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ − 71% (p = 0.007) for unstable angina, Δ − 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ − 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1–9 to 62 patients in calendar weeks 10–16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ − 32% (p = 0.18), ischemic stroke: Δ − 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1–9 (213 patients) and weeks 10–16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020. Conclusions The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.
18
Miner, Brienne, Henry Yaggi, Thomas Gill, Margaret Doyle, Katie Stone, Susan Redline, Kristine Ensrud, Terri Blackwell, and Melissa Knauert. "0321 Poor Agreement Among Self-Reported and Objective Sleep Deficiency Assessments in Older Persons." Sleep 45, Supplement_1 (May 25, 2022): A144—A145. http://dx.doi.org/10.1093/sleep/zsac079.319.
Full textAbstract:
Abstract Introduction Many traditional sleep questionnaires were developed in younger populations and may have poor sensitivity to detect objective sleep deficiency in older persons due to atypical presentations, aging-related decreases in symptom awareness, and different expectations about health. Methods In a secondary analysis of data from the Osteoporotic Fractures in Men (MrOS; Sleep Visit 1) and the Study of Osteoporotic Fractures (SOF Visit 9), we evaluated the prevalence of objective sleep deficiency among persons with scores in the normal range on traditional sleep questionnaires (Pittsburgh Sleep Quality Index [PSQI] <6 and Epworth Sleepiness Scale [ESS] <11). Objective sleep deficiency was established based on presence of sleep-disordered breathing (SDB; apnea hypopnea index [at >4% desaturation] per hour of sleep ≥15 on polysomnography), insufficient sleep duration (average sleep duration <6 hours on actigraphy), or impairment in daytime sustained attention/alertness (falling in the worst quartile of Digit Vigilance Test scores for the sex-specific cohort). Results Average ages were 76±6 and 84±4 years in men and women, respectively. Among men with normal scores on the PSQI and ESS, 359/1527 (25%) had SDB, 428/1519 (28%) had insufficient sleep duration, and 346/1527 (23%) had impaired daytime attention/alertness. Among women with normal scores on both the PSQI and ESS, 72/185 (40%) had SDB, 318/1332 (24%) had insufficient sleep duration, and 140/546 (26%) had impaired daytime attention/alertness. Conclusion A substantial proportion of older men and women with normal scores on traditional sleep questionnaires have objective sleep deficits, suggesting a need to develop instruments to improve detection of sleep deficiency in this population. Support (If Any) American Academy of Sleep Medicine Foundation, Yale Claude D. Pepper Older Americans Independence Center, Patterson Trust, National Institute on Aging
19
FERREIRA, TALITA, CINTIA C. NIVA, RAFAELA DUDAS, RODRIGO ROANI, NATÁLIA DURÃES, ROBÉLIO LEANDRO MARCHÃO, SAMUEL WOOSTER JAMES, MARIE L. C. BARTZ, and GEORGE G. BROWN. "Earthworm species in different land use systems in the state of Goiás and the Federal District of Brazil." Zootaxa 5255, no. 1 (March 15, 2023): 283–303. http://dx.doi.org/10.11646/zootaxa.5255.1.24.
Full textAbstract:
The state of Goiás and the Federal District together cover an area of about 346 thousand km2, including the diversified Cerrado vegetation, also known as the Brazilian Savanna, a biodiversity hotspot with many endangered and endemic species. Much of the Cerrado has been converted to agriculture, but little is known of its earthworms, and the impacts of land use management and agricultural practices on their density and diversity. In the present paper we review the known earthworm species in Goiás and the Federal District based on historical and museum records, and update information on their distribution and populations in different counties and land use systems with data from recent samplings. Five additional species are reported here for the first time, raising the total to 12 species currently known from Goiás, from the families Benhamiidae (1), Glossoscolecidae (1), Megascolecidae (3), Ocnerodrilidae (2) and Rhinodrilidae (5). In the Federal District, an additional 10 species are reported, bringing the total to 23 earthworm species, belonging to the families Benhamiidae (4), Eudrilidae (1), Glossoscolecidae (2), Ocnerodrilidae (1), Lumbricidae (2), Megascolecidae (1) and Rhinodrilidae (12). Native species in Goiás (6) were found in areas with lesser disturbance, such as in native forest and flooded areas/river banks, a phenomenon also observed in the Federal District. On the other hand, the exotic and peregrine species found in Goiás (6) and in the Federal District (9) dominated in disturbed sites, such as perennial crops, agroforestry, annual crops, urban areas, secondary forests, pastures and agropastoral systems, among others. Given the many new species found and the extension of Goiás and the Federal District, further effort is needed to adequately characterize the earthworm fauna of the region, from where many other species are expected.
20
Okur, Yillar, Birsen Yucel, Ebru Atasever Akkas, Mehmet Fuat Eren, Nalan Akgul Babacan, Turgut Kacan, and Saadettin Kilickap. "Effect of the patient's age on radiotherapy-based adverse effect." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19575-e19575. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19575.
Full textAbstract:
e19575 Background: We aim to determine the acute side effects of radiotherapy and the contribution of age to side effect occurrence in patients treated with radiotherapy. Methods: The data of 346 patients having treatment at Cumhuriyet University Radiation Oncology Department in 2010 and 2011 were analyzed. The patients were evaluated according to Radiation Therapy Oncology Group (RTOG) one a week after starting to radiotherapy. Results: There were 167 women (48%) and 179 men (52%). Two-hundred-forty-seven (71%) of the patients were under the age of 65, 99 (29) were above the age of 65. Eastern Cooperative Oncology Group (ECOG) performance situation was 0, 1 and 2 in 278 (80%), 51 (15%) and 19 (5%) patients. Stage 1, 2, 3 and without metastasis stage 4 were found in 30 (9%), 105 (30%), 172 (50%) and 39 (11%) patients. Radiotherapy was applied to 55 head and neck regions (16%), 31 brains (9%), 86 breasts (25%), 30 thoraxes (9%), 52 abdomens (15%) and 90 pelvises (26%). Fifty-four patients (55%) of above the age of 65 received radiotherapy, 45 patients (45%) received chemoradiotherapy. One-hundred-twenty-six patients (51%) of under the age of 65, received radiotherapy and 121 patients (49%) received chemoradiotherapy. For all the patients, the ratio of radiotherapy dependent side effects was 89% (307). The verage time for occurrence was two weeks. When the treatment was over, the number of patients who lost more than five kg was 42 (12%). ECOG difference was seen in 70 (18%) patients. Twelve of them (4%) showed recovery in ECOG performance, 50 (16%) patients showed disruption. Seventy-nine patients (23%) had a interruption in treatment because of the side effects. The occurrence of dermal side effects was higher in the group of patients below the age of 65 and the occurrence of genitourinary side effects was higher in patients above the age of 65. Thedifferences for both of the side effects were statistically significant. Other side effects and time showed no difference between the patients under 65 and patients above 65. Conclusions: The age does not affect the acute side effects of radiotherapy or chemoradiotherapy, so that both groups can tolerate radiotherapy and chemoradiotherapy.
21
Webster, J. R., I. D. Corsor, R. P. Littlejohn, and J. M. Suttie. "Increased winter growth in male red deer calves under an extended photoperiod." Animal Science 65, no. 2 (October 1997): 305–10. http://dx.doi.org/10.1017/s1357729800016623.
Full textAbstract:
AbstractThe growth of male red deer slows during the first winter of life before increasing again during spring. This study aimed to determine if this period of slow growth could be minimized using artificial photoperiods during autumn and winter (10 April (week 1) to 11 September (week 23), southern hemisphere). Four groups of deer (no. = 10) were housed indoors as follows. Two groups were placed on a winter solstice photoperiod (8·5 light (L): 15·5 dark (D)) and given either a natural increase in photoperiod to 11·25L: 12·75D (WSN) or held on 8·5L: 15·5D for 7 weeks followed by an abrupt increase to 11·25L: 12·75D (WSH). One group was exposed to a summer solstice photoperiod of 16L: 8D (SS) and one group exposed to a natural photoperiodic pattern (IC). A fifth group of deer (no. = 10) was maintained outside on a gravelled enclosure under natural changes in photoperiod (OC). All groups were given a diet containing 160 g protein per kg and 11·0 MJ metabolizable energy per kg dry matter (DM) ad libitum. All animals were weighed weekly and group food intake recorded daily. Metatarsal length was measured at weeks 3,17 and 22 from the start of treatments.The major differences occurred between SS and the other groups. After a period of slower growth (weeks 1 to 5, SS = 88 g/day v. 168 g/day other groups, s.e.d. 31·2, P < 0·05), SS grew more rapidly from week 10 (P < 0·01). As a result, SS was heaviest from week 17 (P < 0·05) until the end of the experiment (P < 0·01). The mean growth rate of SS animals from weeks 10 to 23 was 346 g/day compared with 173 g/day (s.e.d. 15·3; P < 0·001) for the other groups. Over the whole experiment, SS animals gained 42·3 kg live weight, compared with 31·1 kg for WSN, 26·6 kg for WSH, 25·1 kg for OC and 23·7 kg for IC (s.e.d. 2·08 kg P < 0·01). The DM intake of SS from week 9 until the end of the experiment averaged 2·04 kg DM per head per day compared with 1·48 (s.e. 0·041) kg DM per head per day for the mean of the other groups. Metatarsal length increased more in SS than the other groups (P < 0·001) between weeks 3 and 17 and was longest in SS at weeks 17 and 22 (P < 0·01). Exposure to a 16L: 8D photoperiod during winter advanced the rapid growth of red deer calves normally associated with spring and summer. This response may be used to advance slaughter dates for venison production.
22
Selvan, Preethi, Katherine Myers-Coffman, Karolina Bryl, Jasmine Tenpa Lama, Brigette Sutton, Jacelyn Biondo, Carrie Cottone, et al. "Recruiting patients with advanced cancer to participate in a non-opioid intervention for chronic pain management." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e14085-e14085. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e14085.
Full textAbstract:
e14085 Background: Chronic pain related to advanced cancer is difficult to treat. In addition to traditional analgesics, non-pharmacological interventions, such as music therapy, may help alleviate pain in this population. Research studies to test the efficacy of these non-pharmacological interventions are necessary and important. However, recruiting patients with advanced cancer to participate in such interventions can be challenging. Identifying effective sources of referrals and barriers to participation may help increase recruitment rates in the future. Methods: We recruited patients with advanced cancer (stage III or IV) with chronic pain from two major hospital systems to participate in a pain management interventional study. The experimental group received individualized music therapy, while the control group received talk therapy. Participants attended six weekly sessions at the hospital and were compensated for time and travel. Recruitment methods included referrals from care teams, advertisement through flyers and posters, EMR chart reviews, and in-person recruitment at multiple infusion centers. Missing data was excluded from analyses. Chi-square tests assessed significant differences between groups. Results: Of 594 patients that were referred to the study, 7% enrolled (n = 40), 35% declined (n = 208), and 58% were ineligible (n = 346). Forty-seven percent (n = 19) of enrolled participants were female; race/ethnic distributions were the following: African American/Black (55%; n = 22), Caucasian/White (28%; n = 11), or other (17%; n = 7). The most effective recruitment method was through self-referral; of the 40 patients enrolled in the study, 9 (23%) were enrolled through this method. There were no statistically significant differences between referral source and enrollment. The top three reasons patients declined to participate included lack of interest (32%; n = 67), lack of time and/or energy (28%; n = 59), and lack of transportation (16%, n = 34). Conclusions: Although there were no differences in referral sources, more patients were enrolled through self-referral or in-person recruitment, showing the power of personal motivation and personal touch. While lack of participation due to interest, time, or energy are hard to overcome, future research should consider campaigns to reach patients who are motivated to participate. In addition to referrals, resources for in-person recruitment and transportation to help alleviate barriers to research participation should be considered.
23
Warner, J. A., and D. W. MacGlashan. "Protein kinase C (PKC) changes in human basophils. IgE-mediated activation is accompanied by an increase in total PKC activity." Journal of Immunology 142, no. 5 (March 1, 1989): 1669–77. http://dx.doi.org/10.4049/jimmunol.142.5.1669.
Full textAbstract:
Abstract We have examined the changes in protein kinase C (PKC) which follow IgE-mediated activation of basophils. Exposure to 0.1 microgram/ml anti-IgE resulted in an increase in total cellular PKC (169 +/- 23% of control, histamine release (HR) = 33 +/- 7%, n = 12) which could be accounted for solely by the increase in membrane-associated PKC. These changes reached a maximum (280 +/- 48%) 1.0 min after challenge and declined to 190 +/- 38% after 5.0 min though histamine release was not complete until 5 to 10 min later. We found a good correlation between the increase in membrane-associated PKC and the eventual release of histamine (rs = 0.902). Donors whose basophils released less than 5% total histamine (n = 3, HR = 3 +/- 1%) showed a partial activation of PKC (173 +/- 18%) though much less than the remaining donors (increase in PKC = 346 +/- 59%, n = 9, HR = 43 +/- 7%). We observed no redistribution of cytosolic PKC at any time following exposure to anti-IgE. In contrast, 0.1 microgram/ml 2-O-tetradecanoyl-phorbol-13-acetate (HR = 36 +/- 3%, n = 3) promoted an increase in total cellular PKC, the loss of 31 +/- 4% of the cytosolic PKC and an 816 +/- 183% increase in membrane-associated PKC. Activation of PKC by anti-IgE was only partially dependent on extracellular calcium. In the absence of calcium, the increase in PKC was approximately 65% (n = 4) of that noted in the presence of 1mM calcium but these levels were sustained over much longer periods, failing to return to base line after 30 min. Higher than normal concentrations of calcium (5 to 10 mM) promoted rapid increases in PKC activity and accelerated the return to base line (back to prechallenge levels by 5 min). Suboptimal concentrations of anti-IgE (0.01 microgram/ml) attenuated the changes in membrane associated PKC and altered the kinetics of the response. The time required to reach maximum activity increased from 1.0 to 5.0 min with a corresponding decrease in the rate at which histamine was released. Higher concentrations of anti-IgE (1.0 microgram/ml) promoted a rapid increase in PKC (maximum increase in PKC = 501 +/- 59%, time = 0.5 min, HR = 28 +/- 2%) followed by an equally rapid return to base line levels.(ABSTRACT TRUNCATED AT 250 WORDS)
24
Masruroh, Ani, and Adek Cerah Kurnia Azis. "MENGGAMBAR ILUSTRASI KARTUN DENGAN TEKNIK SCRIBBLE." Gorga : Jurnal Seni Rupa 11, no. 2 (December 30, 2022): 554. http://dx.doi.org/10.24114/gr.v11i2.39108.
Full textAbstract:
Keywords: abillity, drawing illustration, scribble technique. AbstrakPermasalahan bermula pn latihan menggambar sehingga siswa tidak terampil. Penelitian ini dilakukan untuk mengetahui peningkatan kemampuan siswa menggambar mpakan siswa kelas VIII SMP Negeri 2 Simpang Kiri Kota Subulussaokumentasi. Analisis data menggunakan deskriptif kuantitatif menggunakan statistik uji T. Berdasarkan hasil dari perhitungan uji T dapat disimpulkan bahwa terdapat peningkatan kemampuan menggambar ilustrasi kartun siswa kelas VIII SMP Negeri 2 Simpang Kiri Kota Subulussalam dengan menggunakan teknik scribble dibandingkan sebelum diberi perlakuan. Hal ini dapat dilihat dari nilai rata-rata yang diperoleh peserta didik pretest sebesar 68,44 dan post test sebesar 81, 83.Kata Kunci: kemampuan, menggambar ilustrasi, teknik scribble. Authors:Ani Masruroh : Universitas Negeri MedanAdek Cerah Kurnia Azis : Universitas Negeri Medan References:Adrian, A. (2000). Bagaimana Menggambar. Jakarta: Angkasa.Anwar, K. (2018). Portrait Scribble. Jakarta: Transmedia Pustaka.Gaol, D. U. L., & Mesra, M. (2020). Analisis Proporsi dan Gelap Terang pada Gambar Wajah. Gorga: Jurnal Seni Rupa, 9(2), 342-346.Ginting, J., & Triyanto, R. (2020). Tinjauan Ketepatan Bentuk, Gelap Terang, dan Warna pada Gambar Bentuk Media Akrilik. Gorga: Jurnal Seni Rupa, 9(2), 300-308.Graha, G., & Idris, I. (1982). Pendidikan Seni Rupa. Jakarta: Departemen Pendidikan Dan Kebudayaan.Halawa, W. E., Triyanto, R., Budiwiwaramulja, D., & Azis, A. C. K. (2020). Analisis Gambar Ilustrasi Hombo Batu Nias Gunungsitoli. Gorga: Jurnal Seni Rupa, 9(1), 193-203.Masida, N., & Irawan, I. (2021). Upaya Meningkatkan Pemahaman ISI Dongeng Ditunjukkan dalam Gambar Ilustrasi Siswa Kelas V SD Negeri 32 Kota Ternate. JURNAL DODOTO, 2(01), 39-46.Masnuna, M. (2018). Pengantar Ilustrasi. Jakarta: Indonesia Pustaka.Purnomo, E., & dkk. (2007). Seni Budaya Kelas VIII. Jakarta: Kementrian Dinas Pendidikan.Seragih, Y. G., & Azis, A. C. K. (2021). Tinjauan Hasil Gambar Ilustrasi Kartun dengan Objek Binatang. Ekspresi Seni: Jurnal Ilmu Pengetahuan dan Karya Seni, 23(2), 302-318.Sumardi, S., Mukaddas, A. B., & Faisal, M. (2021). Transformasi Seni Menggambar dengan Teknik Scribble pada Karya Khoirul Anwar di Kota Malang, Jawa Timur. BALOLIPA: Jurnal Pendidikan Seni Rupa, 1(1), 24-35.Surbakti, T. I. P., Zulkifli, Z., Atmojo, W. T., & Mesra, M. (2019). Analisis Kreativitas Siswa Kelas III SD Swasta Yayasan Wanita Kereta Api “YWKA” Medan dalam Pembelajaran Menggambar Binatang. Gorga: Jurnal Seni Rupa, 8(1), 182-186.Sutandur, S., & dkk. (2008). Seni Rupa 2. Jakarta: PT. Tiga Serangkai Pustaka Mandiri.Ulfah, T., & Budiwiwaramulja, D. (2019). Analisis Karya Gambar Ilustrasi Teknik Arsir Siswa Kelas VIII di SMP Swasta Tunas Karya Batang Kuis. Gorga: Jurnal Seni Rupa, 8(1), 279-283.
25
Kim, Richard D., Xiaoyun Pan, Helene Ostojic, Yiqiao Zhang, Orsolya Lunacsek, Federica Pisa, and Marc Peeters. "Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 48. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.48.
Full textAbstract:
48 Background: Anecdotal evidence suggests that some pts with mCRC experience significantly longer responses to REG in clinical care settings, including a case exceeding 9 years. However, comprehensive studies on long-term responders to REG are lacking. We evaluated demographic/clinical characteristics of pts with long-term response (LTR) to REG using duration of treatment (DOT) as a surrogate for treatment response. Methods: This was a retrospective cohort study using the US nationwide de-identified Flatiron Health Electronic Health Record-derived database. The study period was January 1, 2013 to May 31, 2023, and adult pts with mCRC who initiated REG monotherapy (index date) from July 1, 2013 to December 31, 2022 were included. DOT for pts with LTR of ≥5 months (LTR5 [primary objective]; mos) or ≥4 mos (LTR4 [secondary objective]) were determined. Results: A total of2,326 eligible pts (median age 64 yrs; 56% male) had initiated REG during the study period. Overall, 346 pts (15%; median age 65 yrs) had LTR5 and 503 pts (22%; median age 65 yrs) had LTR4. Among pts with LTR5, 46% had stage IV disease at initial diagnosis, 68% had ECOG performance status (ECOG PS) 0‒1 at index, 64% received prior bevacizumab (BEV), and of pts tested at index with results, the median carcinoembryonic antigen (CEA) level was 35 ng/mL, and 51% and 5% had a KRAS and BRAF mutation at index, respectively; pts with LTR4 had similar characteristics (Table). Median time from initial CRC diagnosis to index date was 39.2 mos for pts with LTR5 and 38.6 mos for pts with LTR4. Of pts who initiated REG before 2019 (n = 1,070), 14% had LTR5 and 21% had LTR4; of pts who initiated REG from 2019 onwards (n = 1,256), 16% had LTR5 and 22% had LTR4. Among pts with LTR5, 33% and 23% had received REG as third-line (3L) or fourth-line (4L) treatment, respectively; among pts with LTR4, 34% and 23% had received REG as 3L or 4L treatment, respectively. Median time to discontinuation of REG was 7.3 (95% CI 6.9, 7.8) mos in pts with LTR5 and 6.0 (95% CI 5.7, 6.2) mos in pts with LTR4. Median follow-up time (from index date) was 13.3 mos and 11.1 mos in pts with LTR5 and LTR4, respectively. Conclusions: This is the first large-scale RW evidence study to describe demographic/clinical characteristics of pts with LTR to REG. Pts demonstrating LTR typically had favorable ECOG PS at REG initiation, less advanced disease at initial diagnosis, and the majority had received prior BEV. [Table: see text]
26
Patel, Priti, Mayra Telesca, and De-Hui Ku. "The Comparison of Fibrin Monomer (FM) Performance to Other Activation Markers (TAT, PF1.2 and DD)." Blood 118, no. 21 (November 18, 2011): 5259. http://dx.doi.org/10.1182/blood.v118.21.5259.5259.
Full textAbstract:
Abstract Abstract 5259 In this study, we attempted to determine the performance of the soluble fibrin monomer complex (SFMC) test in comparison to known activation markers, such as prothrombin fragment 1.2 (PF1.2), thrombin antithrombin complex (TAT) and d-dimer (DD). We have used the STA(R)-Liatest FM and STA(R)-Liatest D-Di kits to measure the SFMC and d-dimer levels. A total of 25 patients were included in this study. The data and demographic information are shown in the table below. ID GENDER AGE FM TAT PF1.2 D-dimer 1 M 66 0.42 2.3 1988 0.05 2 F 31 27.93 >60.0 >12000 2.39 3 F 24 3.41 14.1 1367 0.48 4 F 61 2.22 7.7 335 0.63 5 F 18 4.61 6.9 940 0.22 6 F 38 156.52 43.5 >12000 10.37 7 F 20 0.42 2.2 149 0.66 8 F 21 0.42 2.4 143 0.24 9 M 44 >150 15.4 11043 5.5 10 F 42 3.4 <2.0 134 0.24 11 M 46 0 4.8 271 0.3 12 M 76 90.73 29.4 1712 >20.0 13 F 61 3.41 3.8 484 0.52 14 M 1 0.1 3.8 116 0.33 15 F 33 4.2 37 6346 2.03 16 F 35 3.2 2.6 325 0.09 17 F 23 1.1 4.7 232 0.2 18 M 64 2.3 2.6 189 0.15 19 M 1 1.7 2.9 253 0.49 20 M 64 2.2 33.2 451 2.43 21 M 60 1.6 2.9 126 0.42 22 F 55 2.2 2.6 189 0.97 23 F 65 1.3 2.3 79 0.25 24 F 39 3.6 8.1 222 0.18 25 M 2 4.8 <2.0 109 0.53 Reference range >6.0 ug/mL <4 mcg/L 41–372 pmol/L <0.45 ug/mL The data indicate that in 16 out 25 patients, the SFMC levels are correlated with TAT and PF1.2. Only 3 out of 25 patients have elevated TAT and PF1.2 with normal SFMC levels. Therefore, our data would tend to indicate that SFMC level could be used as an activation marker to assess an ongoing prothrombotic process. In order to more fully determine the efficacy of the SFMC assay, we will obtain a detailed clinical history for the cases shown above. Disclosures: No relevant conflicts of interest to declare.
27
Veldhorst, Margriet A. B., Klaas R. Westerterp, Anneke J. A. H. van Vught, and Margriet S. Westerterp-Plantenga. "Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance." British Journal of Nutrition 104, no. 9 (June 22, 2010): 1395–405. http://dx.doi.org/10.1017/s0007114510002060.
Full textAbstract:
Two types of relatively high-protein diets, with a normal or low proportion of carbohydrates, have been shown effective for weight loss. The objective was to assess the significance of the presence or absence of carbohydrates and the proportion of fat in high-protein diets for affecting appetite suppression, energy expenditure, and fat oxidation in normal-weight subjects in energy balance. Subjects (aged 23 (sd3) years and BMI 22·0 (sd1·9) kg/m2) were stratified in two groups. Each was offered two diets in a randomised cross-over design: group 1 (n22) – normal protein (NP; 10, 60 and 30 % energy (En%) from protein, carbohydrate and fat), high protein (HP; 30, 40 and 30 En%); group 2 (n23) – normal protein (NP-g; 10, 60 and 30 En%), high protein, carbohydrate-free (HP-0C; 30, 0 and 70 En%) for 2 d; NP-g and HP-0C were preceded by glycogen-lowering exercise (day 1). Appetite was measured throughout day 2 using visual analogue scales (VAS). Energy expenditure (EE) and substrate oxidation (respiratory quotient; RQ) were measured in a respiration chamber (08.00 hours on day 2 until 07.30 hours on day 3). Fasting plasma β-hydroxybutyrate (BHB) concentration was measured (day 3). NP-g and NP did not differ in hunger, EE, RQ and BHB. HP-0C and HPv.NP-g and NP, respectively, were lower in hunger (P < 0·05;P < 0·001) and RQ (P < 0·01;P < 0·001) and higher in EE (P < 0·05;P = 0·07) and BHB (P < 0·05;P < 0·001). Hunger and RQ were lower with HP-0C than HP (693 (sd208)v.905 (sd209) mm VAS × 24 h,P < 0·01; 0·76 (sd0·01)v. 0·81 (sd0·02),P < 0·01); BHB was higher (1349 (sd653)v.332 (sd102) μmol/l;P < 0·001). ΔHunger, ΔRQ, and ΔBHB were larger between HP-0C–NP-g than between HP–NP ( − 346 (sd84)v.− 107 (sd52) mm VAS × 24 h,P < 0·01; − 0·09 (sd0·00)v.− 0·05 (sd0·00),P < 0·001; 1115 (sd627)v.104 (sd42) μmol/l,P < 0·001). In conclusion, appetite suppression and fat oxidation were higher on a high-protein diet without than with carbohydrates exchanged for fat. Energy expenditure was not affected by the carbohydrate content of a high-protein diet.
28
Duong, Hien K., Anna Koo, Lisa Rybicki, Ed Copelan, Matt Kalaycio, Ronald Sobecks, Robert M. Dean, et al. "Obese Patients Have Improved Survival Following Autologous Hematopoietic Stem Cell Transplantation." Blood 120, no. 21 (November 16, 2012): 1989. http://dx.doi.org/10.1182/blood.v120.21.1989.1989.
Full textAbstract:
Abstract Abstract 1989 High-dose chemotherapy followed by autologous stem cell transplant can improve long-term outcome of patients with hematologic malignancies. Outcomes following transplant are variable. Obesity has implications for stem cell mobilization, chemotherapy administration, and medication dosing. We analyze the impact of obesity on transplant outcomes including neutrophil recovery, platelet recovery, length of hospital stay, and survival. From 1/2004 to 12/2009, 573 patients underwent autologous stem cell transplant. From these patients, 17 were excluded due to incomplete data. Of the remaining 556 patients, the median age was 53 years, and 346 (62%) were male. The diagnoses were 286 (51%) non-Hodgkin lymphoma, 161 (29%) multiple myeloma, 91 (16%) Hodgkin lymphoma, and 18 (3.2%) other. A majority of these patients (93%) had received 3 or less prior chemotherapy regimens. Most patients (76%) had not received prior radiation therapy. Most patients had chemosensitive disease (92% were in complete or partial remission) at time of transplant. For stem cell mobilization regimen, 376 (68%) received chemotherapy and G-CSF, 176 (32%) received G-CSF alone, and 4 (<1%) received G-CSF and Plerixafor. For a preparative regimen, 360 (65%) received busuflan/etoposide/cyclophosphamide, 125 (23%) received melphalan, and 71 (13%) received busulfan/cyclophosphamide. Patients were categorized into four groups based on the body mass index (BMI): underweight (BMI<18.5), normal (18.5–24.9), overweight (25.0–29.9), or obese (≥30.0). Using these definitions, there were 5 (1%) underweight, 133 (24%) normal, 188 (34%) overweight, and 230 (41%) obese patients. Underweight and normal were combined into a single group due to the small number of underweight patients. Baseline and transplant characteristics of these patients are listed in Table 1. Variables were compared among BMI groups using the Chi-square test (categorical variables), Kruskal-Wallis test (continuous variables), or log-rank test (survival). Cox proportional hazards analysis was used to identify prognostic factors for survival. On univariable and multivariable analyses, obese patients demonstrate better survival than those who are not obese (hazard ratio 0.73, P=0.026; Figure 1). In conclusion, obesity has no impact on neutrophil or platelet recovery, length of transplant hospitalization, or 100-day mortality. Obese patients appear to have improved overall survival. The reasons for this are unclear, but may have to do with higher total dose of chemotherapy for the preparative regimen. Although obesity is associated with many co morbidities and possibly more aggressive disease, these patients do not have cancer cachexia and may have other protective benefits. Table 1. Patient and transplant characteristics according to BMI Underweight/ Normal N = 138 Overweight N = 188 Obese N = 230 Variable N (%) N (%) N (%) P-value Gender Male 63 (46) 136 (72) 147 (64) <0.001 Female 75 (54) 52 (28) 83 (36) Age, years Median (range) 50 (20–74) 55 (20–73) 54 (19–75) 0.013 Number of prior chemotherapy regimens ≤ 3 130 (94) 177 (94) 212 (92) 0.65 >3 8 (6) 11 (6) 18 (8) Prior radiation therapy Yes 38 (28) 45 (24) 53 (23) 0.61 No 100 (72) 143 (76) 177 (77) Diagnosis NHL 74 (54) 98 (52) 114 (50) 0.025 MM 28 (20) 53 (28) 80 (35) HL 33 (24) 30 (16) 28 (12) Other 3 (2) 7 (4) 8 (4) Disease status at transplant CR/PR 120 (87) 172 (91) 217 (94) 0.048 Active disease 18 (13) 16 (9) 13 (6) Mobilizing regimen G-CSF+chemotherapy 106 (77) 126 (67) 144 (63) 0.05 G-CSF alone 32 (23) 61 (32) 83 (36) G-CSF + Plerixafor 0 (0) 1 (0.5) 3 (1) Preparative regimen Bu/VP/Cy 94 (68) 128 (68) 138 (60) 0.22 Melphalan 30 (21) 34 (18) 61 (27) Bu/Cy 14 (10) 26 (14) 31 (13) CD34+ dose, × 106/kg Median (range) 6.19 (2.11–47.97) 5.67 (2.06–65.18) 7.01 (1.62–51.90) 0.21 Days to ANC > 500 Median (range) 11 (9–13) 11 (9–17) 10 (9–15) 0.36 Days to platelet > 20,000 Median (range) 14 (6–129) 14 (5–432) 14 (3–46) 0.48 Length of hospital stay Median (range) 21 (13–30) 20 (13–74) 20 (12–37) 0.08 100-day mortality Yes 9 (7) 9 (5) 4 (2) 0.06 No 129 (93) 179 (95) 226 (98) Figure 1: Survival outcomes according to BMI Figure 1:. Survival outcomes according to BMI Disclosures: No relevant conflicts of interest to declare.
29
Lob, Sibylle, Krystyna Kazmierczak, Wei-Ting Chen, Yivonne Khoo, Kanchan Balwani, Katherine Young, Mary Motyl, and Daniel F. Sahm. "1581. In Vitro Activity of Ceftolozane/Tazobactam against Pseudomonas aeruginosa from ICU and Non-ICU Patients with Respiratory Tract Infections in the Asia/Pacific region – SMART 2016-2018." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S788. http://dx.doi.org/10.1093/ofid/ofaa439.1761.
Full textAbstract:
Abstract Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Elevated antimicrobial resistance rates have been reported among pathogens collected in ICUs. Using isolates collected in Asia/Pacific as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against P. aeruginosa from patients with respiratory tract infections (RTI) in ICU and non-ICU wards. Methods In 2016-2018, 55 clinical laboratories in 11 Asia/Pacific countries collected 2530 P. aeruginosa isolates from RTI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints. C/T-nonsusceptible isolates (except those from India) were screened by PCR and sequencing for genes encoding β-lactamases. Results Susceptibility to C/T in Asia/Pacific was 85.3% in ICUs and 92.2% in non-ICUs, 15-23 percentage points and 13-19 percentage points, respectively, higher than to meropenem, cefepime, and piperacillin-tazobactam. C/T maintained activity against 58.8% and 69.4% of meropenem-nonsusceptible isolates from ICU (n=294) and non-ICU patients (n=346), respectively. Acquired β-lactamases were detected in 64% of C/T-nonsusceptible isolates from ICUs (n=90; 54% MBL-positive, 1% GES carbapenemase-positive, 9% ESBL-positive) and in 47% of C/T-NS isolates from non-ICUs (n=86; 33% MBL-positive, 6% GES-carbapenemase-positive, 8% ESBL-positive). The table presents country-level rates of C/T-susceptible and carbapenemase-positive P. aeruginosa for countries with n >20 in both ICU and non-ICU subsets. Table Conclusion In Asia/Pacific overall, C/T maintained susceptibility rates >85% in both ICU and non-ICU wards against P. aeruginosa isolates from RTI, with rates >91% in most countries. Susceptibility was lower in countries with higher rates of carbapenemase-positive P. aeruginosa. C/T could provide an important treatment option for RTI infections caused by P. aeruginosa in the Asia/Pacific region. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
30
Bhatnagar, Surbhi, Alexis Mitelpunkt, Juliana J. Rizzo, Nanhua Zhang, Tess Guzman, Ryan Schuetter, Jilda Vargus-Adams, et al. "Mental Health Diagnoses Risk Among Children and Young Adults With Cerebral Palsy, Chronic Conditions, or Typical Development." JAMA Network Open 7, no. 7 (July 19, 2024): e2422202. http://dx.doi.org/10.1001/jamanetworkopen.2024.22202.
Full textAbstract:
ImportanceMental health (MH) issues in children with cerebral palsy (CP) are poorly understood compared with other pediatric populations.ObjectiveTo examine MH diagnosis code assignment among children and young adults with CP and compare with typically developing (TD) and chronic condition (CC) pediatric populations.Design, Setting, and ParticipantsThis case-control study used International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to create a CP case set and CC and TD control sets using electronic health record data of children and young adults from a large tertiary care children’s hospital in the midwestern United States between 2010 and 2022. Case-control matching was performed to control for demographic factors. Data were analyzed from June to December 2023.ExposuresAll MH diagnosis codes were mapped to ICD-10-CM and categorized using Clinical Classifications Software Refined (CCSR).Main Outcomes and MeasuresThe incidence rates of MH CCSR categories were calculated. Descriptive and comparative statistics were used to evaluate the significance and odds associated with factors.ResultsData from 216 794 individuals (mean [SD] baseline age, 4.3 [5.1] years; 118 562 [55%] male) were analyzed, including 3544 individuals with CP, 142 160 individuals with CC, and 71 080 TD individuals. The CP cohort spread across Gross Motor Function Classification System (GMFCS) levels I (981 individuals [28%]), II (645 individuals [18%]), III (346 individuals [10%]), IV (502 individuals [14%]), and V (618 individuals [17%]). Rates varied significantly for anxiety (824 individuals with CP [23%]; 25 877 individuals with CC [9%]; 6274 individuals with TD [18%]), attention-deficit/hyperactivity disorder (534 individuals with CP [15%]; 22 426 individuals with CC [9%]; 6311 individuals with TD [16%]); conduct or impulse disorder (504 individuals with CP [14%]; 13 209 individuals with CC [5%]; 3715 individuals with TD [9%]), trauma or stress disorders (343 individuals with CP [10%]; 18 229 individuals with CC [8%]; 5329 individuals with TD [13%]), obsessive-compulsive disorder (251 individuals with CP [7%]; 3795 individuals with CC [1%]; 659 individuals with TD [3%]), depression (108 individuals with CP [3%]; 12 224 individuals with CC [5%]; 4007 individuals with TD [9%]), mood disorders (74 individuals with CP [2%]; 4355 individuals with CC [2%]; 1181 individuals with TD [3%]), and suicidal ideation (72 individuals with CP [2%]; 7422 individuals with CC [5%]; 3513 individuals with TD [5%]). There was significant variation in odds of MH diagnoses by GMFCS level (I-II vs III-V: odds ratio [OR], 1.23; 95% CI, 1.09-1.40; P = .001). Among individuals with CP, males were more likely than females to have diagnosis codes for conduct or impulse disorders (OR, 1.41; 95% CI, 1.16-1.73) and attention-deficit/hyperactivity disorder (OR, 1.41 [95% CI, 1.15-1.73]). Black individuals, compared with White individuals, were more likely to have diagnoses for obsessive-compulsive disorder (OR, 1.57 [95% CI, 1.14-2.16]), other mood disorders (OR, 1.85 [95% CI, 1.01-3.38]), and trauma or stress disorders (OR, 1.94 [95% CI, 1.44-2.63]). Odds for trauma or stress disorders were elevated for individuals who identified as other races compared with White individuals (OR, 2.80 [95% CI, 2.03-3.87]).Conclusions and RelevanceIn this case-control study of children and young adults with CP and matched comparisons, anxiety and conduct or impulse diagnoses were higher in individuals with CP. The lower diagnosis rates of depression and suicidal ideation may indicate underdiagnosis among individuals with CP. There is likely a need for assessment tools that are more suitable for children with CP.
31
Yamaguchi, Kensei, Yoon-Koo Kang, Do-Youn Oh, Shunsuke Kondo, Sun Young Rha, Yasutoshi Kuboki, Manabu Morimoto, et al. "Phase I study of BI 754091 plus BI 754111 in Asian patients with gastric/gastroesophageal junction or esophageal cancer." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 212. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.212.
Full textAbstract:
212 Background: Dual blockade of immune checkpoint molecules, PD-1 and LAG-3, has been proposed to restore T-cell function and thus enhance antitumor responses. This Phase I trial evaluated BI 754091 (anti-PD-1) with BI 754111 (anti-LAG-3) antibodies in Asian pts with advanced solid tumors (NCT03433898). Here, we present results from pts with anti-PD-(L)1 inhibitor-naïve gastric/gastroesophageal junction or esophageal cancer (Cohorts A and B). Methods: In Parts 1 and 2 (dose escalation), the recommended dose for the combination was determined as BI 754091 240 mg + BI 754111 600 mg IV Q3W. In Part 3, the combination was assessed in expansion cohorts including pts with gastric/gastroesophageal junction cancer (Cohort A) and esophageal cancer (Cohort B). Eligible pts had received ≥1 line of prior systemic therapy but no prior anti-PD-(L)1 therapy. The primary endpoint in Part 3 was objective response (OR; confirmed complete response or partial response [PR]) per RECIST 1.1. Results: In Cohort A/B, 36/37 pts were treated:26/31 (72/84%) male, median age 60/63 years. Patients were enrolled in Taiwan (1/7 pts, 3/19%), Japan (12/27 pts, 33/73%) or Korea (23/3 pts, 64/8%). The median number of regimens of prior systemic therapy was 2/2 (Cohorts A/B, range: 16/14). All pts in Cohort B had squamous cell carcinoma. At the time of analysis, pts in Cohort A/B had undergone a median of 84/73 days on treatment (range: 31346/8325), from the start of treatment until the date of snapshot, death or discontinuation. Confirmed OR (PR) was observed in 4/7 pts in Cohorts A/B; overall response rate (ORR) was 11% and 19%. Stable disease (SD) was observed in 10/8 (28/22%) pts in Cohorts A/B and overall disease control rate was 39/41%. In Cohorts A/B, adverse events (AEs) and treatment-related AEs were experienced by 30/34 (83/92%) and 12/22 (33/59%) pts, respectively. The most commonly reported AEs were pyrexia (25/19%), decreased appetite (17/19%), increased aspartate aminotransferase (11/14%), anemia (11/11%) and nausea (6/14%). In Cohort A/B, 9/15 (25/41%) pts experienced immune-related AEs, most commonly rash in Cohort A (4 pts; 11%) and hyperthyroidism in Cohort B (4 pts; 11%). In Cohorts A/B, 2/6 (6/16%) patients experienced AEs leading to discontinuation of treatment. Conclusions: Treatment was well tolerated and preliminary antitumor activity was seen. Addition of LAG3 did not improve ORR beyond that expected for an anti-PD-1 monotherapy in gastric and esophageal cancer without patient selection. Clinical trial information: NCT03433898. [Table: see text]
32
Corash, Laurence, Fabrice Cognasse, Jean-Claude Osselaer, Natalie Messe, and Olivier Garraud. "Release of Immune Modulation Factors from Platelet Concentrates during Storage after Photochemical Pathogen Inactivation." Blood 108, no. 11 (November 16, 2006): 941. http://dx.doi.org/10.1182/blood.v108.11.941.941.
Full textAbstract:
Abstract Background. Platelets (plt) prepared for transfusion contain multiple molecules that modulate immune function, mediate acute transfusion reactions, induce immune responses, and affect hemostasis. These cytokines/chemokines are secreted differentially from plt during storage (Transfusion2006;46:1184), and may be affected by processing, including pathogen inactivation. Aims. The INTERCEPT Blood System (IBS) for platelets utilizes amotosalen-HCl (S-59) with ultraviolet A (UVA) light to inactivate a broad spectrum of pathogens and leukocytes. This study was designed to evaluate the effects of photochemical treatment on in vitro release of immune modulation molecules after processing during 7 days (d) of storage. Methods. Platelet concentrates (n = 10) collected by aphaeresis (CPA) with process leuko-reduction (< 106) containing 8.15x1011 ± 0.8 platelets were suspended in 35% donor plasma and 65% platelet additive solution (Intersol, Baxter, France) and divided into two equal components. One served as an untreated control (C) and the other was prepared with 150 uM amotosalen and a 3 J/cm2 UVA photochemical treatment (PCT) and stored at 22°C with shaking for 7 days. Platelet concentration (106/uL), pH and levels of immune modulation factors were measured: CD62p(ng/mL), PDGF-AB(ng/mL), IL8(pg/mL), sCD40L(pg/mL), IL1β(pg/mL) and TNFα(pg/mL). The concentration of each factor was determined by specific enzyme linked immunosorbent assays in plt and supernatant (s) fractions isolated from stored PCT and C plt components. Mean values ± SD were calculated and compared by paired t-test. Results. Platelet content, pH and cytokine/chemokine content and release from CPA prepared with photochemical treatment were not statistically different (p > 0.05) from C during 7 d of storage (Table). From d1 to d7, the pH of PCT and C units decreased similarly, but remained within acceptable ranges. No detectable IL1β and TNFα were observed in PCT or C CPA. During platelet storage CD62p, PDGF-AB, IL8, and sCD40L increased similarly in supernatants of PCT and C units. The increase in supernatant levels correlated with a decrease of these cytokines in plt. Platelets in PCT and C retained measurable levels of CD62, IL8, sCD40L and PDGF-AB though 7 d. Levels of sCD40L demonstrated marked variation. Conclusions. Cytokines increased moderately in the supernatants of CPA and decreased in platelets during storage. After 7 d C and PCT platelets in CPA retained detectable levels of cytokines. PCT had no differential influence on release of immune modulation molecules in vitro over 7 d of storage. Day O O 5 5 7 7 Product C PCT C PCT C PCT pH 7.1 ±.1 7.1 ±.1 6.9 ±.1 6.8 ±.1 6.9 ±.1 6.8 ±.1 Plt ct 1.29 ±.3 1.30 ±.2 1.30 ±.3 1.19 ±.2 1.27 ±.2 1.18 ±.2 CD62p-s 89 ± 21 87 ± 17 110 ± 23 115 ± 27 117 ± 22 119 ± 25 CD62p-plt 149 ± 33 151 ± 33 141 ± 23 141 ± 25 139 ± 25 139 ± 26 PDGF-s 14.5 ± 3.5 13.6 ± 3.5 17.7 ± 2.4 15.8 ± 1.5 18.0 ± 2.1 17.5 ± 1.8 PDGF-plt 28.3 ± 3.5 30.3 ± 3.1 25.2 ± 3.6 24.9 ± 2.5 23.2 ± 4.0 23.3 ± 3.3 IL8-s 107 ± 17 108 ± 14 136 ± 42 116 ± 9 123 ± 20 120 ± 22 IL8-plt 135 ± 29 134 ± 28 110 ± 11 117 ± 12 103 ± 17 119 ± 32 CD40L-s 51 ± 86 66 ± 94 172 ± 157 237 ± 214 188 ± 198 201 ± 167 CD40L-plt 990 ± 805 1098 ± 747 485 ± 373 474 ± 331 346 ± 293 314 ± 282
33
Kumar, Shaji, Smriti Shrestha, Mei-Jie Zhang, Angela Dispenzieri, Gustavo A. Milone, Sagar Lonial, and Parameswaran N. Hari. "Allogeneic Stem Cell Transplantation (SCT) for Multiple Myeloma (MM) - What Has Changed? : A CIBMTR Analysis From 1989 – 2005." Blood 114, no. 22 (November 20, 2009): 54. http://dx.doi.org/10.1182/blood.v114.22.54.54.
Full textAbstract:
Abstract Abstract 54 Despite its curative potential, the role of allogeneic stem cell transplant (allo-SCT) in MM has been limited by high treatment related mortality (TRM). Autologous stem cell transplant (auto-SCT) thus remains the standard of care for eligible patients (pts) with MM. Recently interest in allo-SCT has been increasing due to the incurable nature of MM, better risk stratification models, improved supportive care and finally the increasing experience with less toxic reduced intensity conditioning. We analyzed the trends in practice of allo-SCT for MM over the past two decades. A total of 1211 pts undergoing allo-SCT for MM between 1989 and 2005, reported to the CIBMTR were analyzed in three cohorts based on year of allo-SCT: 1989–1994 (n=346), 1995–2000 (n=285), and 2001–2005 (n=580). Probabilities of progression-free survival (PFS) and overall survival (OS) and cumulative incidence estimates of TRM and relapse were calculated. Patient characteristics are summarized in table 1. Patients transplanted in the later cohort (2001–2005) were of higher age with 53% above age 50 years (vs. 12% in 1989–1994). There was decreasing use of myeloablative regimens and bone marrow grafts over time (82% vs. 62% vs. 9% for myeloablative regimens and 99%, 62% and 13% for marrow grafts respectively). Increasing number of pts in the later cohort received an auto-SCT prior to allo-SCT (Table 1). The proportion of unrelated allo-SCTs increased over time (5% vs. 21% vs. 33%). Graft versus host (GVH) prophylaxis changed over time with increasing use of cyclosporine with agents other than methotrexate and increasing use of ATG in the recent years. Median survival increased over the three time periods from 1989 – 2005: 11.1 months (mos.) vs. 12.2 mos vs. 20.3 mos. The 100 day mortality decreased steadily over successive time periods; 35% (95% CI; 29–31), 29% (24–35) and 19% (16–23) respectively. Similarly, the TRM at 5 years remained steady between the first two periods, but decreased in the last period (40 & 48% vs. 29%). The incidence of chronic GVHD increased in the later cohort but the incidence of acute GVHD was similar over the years. While PFS was the lowest for the most recent group (15% at 5 years), the overall survival at 5 years was similar among the groups (30, 32, and 29 mos). Long term PFS at 10 years was 18% in the 1989–1994 cohort and 17% in 1995–2000. Long term OS at 10 years was 23% in 1989 – 1994 and 1995–2000 cohorts. Results are summarized in table 1. A clear trend towards reduced intensity conditioning, unrelated donor SCT, use of PBSC grafts and selection of older patients was noted. There was increasing use of tandem auto-allo SCT with an increasing proportion of patients with a prior auto-SCT. While the TRM has decreased significantly in the last cohort, this did not translate into an improvement in survival primarily because of increased risk of relapse in the latter cohort. Long term (>10yr) progression free survival which may approach a cure has remained unchanged over the past two decades at <20%. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.
34
Lisukov, Igor, Alexander Kulagin, Alexey Maschan, Elena Shilova, Kudrat Abdulkadyrov, Andrey Zaritskiy, Valentina Ivanova, et al. "Effect of Eculizumab on Physician-Reported Symptoms in the Russian Cohort of the Paroxysmal Nocturnal Hemoglobinuria (PNH) International Registry." Blood 124, no. 21 (December 6, 2014): 5163. http://dx.doi.org/10.1182/blood.v124.21.5163.5163.
Full textAbstract:
Abstract Background: Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disease that can lead to life-threatening complications including thrombotic events (TE), chronic kidney disease (CKD) and pulmonary hypertension. In 2011 the International PNH Registry was implemented in the Russian PNH cohort to assess the natural history of PNH and the effects of treatment with eculizumab. Aims:We aim to evaluate the change from baseline to last follow-up in physician-reported symptoms, LDH and hemoglobin concentration in treated and untreated PNH patients. Design and methods: The international PNH Registry is a non-interventional, prospective, multicenter observational study. The study population of this analysis comprised the Russian cohort of the Registry: all patients had a confirmed diagnosis of PNH according to international guidelines. As per local guidelines, blood transfusion dependency and a history of TE were the main indications for treatment with eculizumab. Data are presented as descriptive statistics only. The reporting period includes time from baseline until the earliest of: death; bone marrow transplant; discontinuation from the Registry; discontinuation from eculizumab; last follow-up in the Registry. Results: As of June 2014, the international PNH Registry has enrolled 479 patients from Russia, 75 patients were ever-treated with eculizumab (15.7%), among whom 60 had available data. The median (range) duration of follow-up of patients after eculizumab treatment was 0.8 (-0.7 – 1.9) years and the median years (range) from disease onset to the start of eculizumab treatment was 8.1 (1 – 30) years. One patient discontinued treatment due to the disappearance of PNH clones and disease manifestations. Fifteen deaths were reported during the reporting period; all in patients never treated with eculizumab. Table 1. History of medical events at baseline All patients (N = 464) Ever-treated with Eculizumab (N = 60) Never-treated patients (N = 404) History of BMD, n (%) 423* 313 (74) ongoing 39* 12 (31) ongoing 384* 301 (78) ongoing History of TE, n (%) 436* 30 (7) 39* 9 (23) 397* 21 (5) History of any RBC transfusion, n (%) 385* 300 (78) 39* 26 (67) 346* 274 (79) RBC transfusion in past 12 months, n (%) 419* 245 (59) 29* 22 (76) 390* 223 (57) History of CKD, n (%) 435* 24 (6) 39* 1 (3) 396* 23 (6) History of pulmonary hypertension, n (%) 435* 11 (3) 39* 4 (10) 396* 7 (2) *number of patients with available data Table 2. Change from baseline to last follow up for physician-reported symptoms All patients Ever-treated with eculizumab Never-treated patients Abdominal pain, n (%): Improved No change Worsened N=196 33 (17) 145 (74) 18 (9) N=29 15 (52) 10 (35) 4 (14) N=167 18 (11) 135 (81) 14 (8) Dysphagia, n (%): Improved No change Worsened N=195 17 (9) 162 (83) 16 (8) N=29 7 (24) 20 (69) 2 (7) N=166 10 (6) 142 (86) 14 (8) Dyspnea, n (%): Improved No change Worsened N=196 55 (28) 127 (65) 14 (7) N=29 15 (52) 12 (41) 2 (7) N=167 40 (24) 115 (69) 12 (7) Fatigue, n (%): Improved No change Worsened N=199 23 (12) 169 (85) 7 (4) N=29 4 (14) 25 (86) – N=170 19 (11) 144 (85) 7 (4) Hemoglobinuria, n (%): Improved No change Worsened N=196 29 (15) 156 (80) 11 (6) N=28 12 (43) 16 (57) – N=168 17 (10) 140 (83) 11 (7) Median (Q1, Q3) Hb concentrations at baseline in ever-treated and never-treated patients were 7.3 (6.3, 9.2) g/dL and 9.0 (7.2, 11.3) g/dL, respectively, and median (Q1, Q3) changes in Hb concentration from baseline to last follow up were 2.1 (1.2, 3.8) g/dL and 0.75 (-0.4, 2.5) g/dL, respectively. Median (Q1, Q3) LDH level at baseline in ever-treated and never-treated patients were 6.0 (3.6, 8.7) x the upper limit of normal (ULN) and 1.1 (0.8, 1.8) x ULN, respectively, and median (Q1, Q3) changes in LDH level from baseline to last follow up were -4.8 (-6.9, -1.9) and 0.0 (-0.2, 0.3) x ULN, respectively. Conclusion: This analysis represent the first report on longitudinal outcomes during eculizumab therapy in Russian patients included in the international PNH Registry and are considered essential for planning patients' follow-up, including monitoring of therapeutic effects and prophylaxis against break-through hemolysis. Overall, the data show an improvement in physician-reported symptoms and reduced hemolysis, as measured by plasma LDH level, in patients treated for a relatively short period of time. Disclosures Lisukov: Alexion: Honoraria. Kulagin:Alexion: Honoraria. Shilova:Alexion: Honoraria. Afanasyev:Alexion: Honoraria.
35
Fujisawa, Shin, Keitaro Matsuo, Shuichi Mizuta, Hideki Akiyama, Yasunori Ueda, Yasutaka Aoyama, Yoshihiro Hatta, et al. "Imatinib-Based Chemotherapy for Newly Diagnosed BCR–ABL Positive Acute Lymphoblastic Leukemia: Japan Adult Leukemia Study Group (JALSG) Ph+ALL208 Study." Blood 124, no. 21 (December 6, 2014): 932. http://dx.doi.org/10.1182/blood.v124.21.932.932.
Full textAbstract:
Abstract Introduction: The outcome of BCR–ABL positive acute lymphoblastic leukemia (ALL) has drastically improved since the introduction of imatinib. We recently reported the clinical results of the Japan Adult Leukemia Study Group (JALSG) ALL-202 study at the 51th ASH Annual Meeting. Most patients (97.1%) achieved complete remission (CR) and 9% of them relapsed within 100 days after CR. In addition, 60% of patients received allogeneic stem cell transplantation during their first CR, and the 3-year overall survival (OS) rate was 57%. We now present the data of the subsequent JALSG Ph+ALL208 study, where we have modified a part of consolidation therapy to prevent early relapse after achieving CR. Methods: The JALSG Ph+ALL208 study was a phase 2 trial for patients newly diagnosed with BCR–ABL positive ALL. Imatinib at a dose of 600 mg/day was administered from day 8 to day 42 combined with daunorubicine (DNR), cyclophosphamide (CPM), vincristine (VCR) and prednisolone (PSL) for induction therapy. Consolidation therapy comprised course 1 (C1: high-dose methotrexate and high-dose cytarabine with imatinib for 18 days) and course 2 (C2: DNR, CPM, VCR, and PSL with imatinib for 20 days). C1 and C2 were repeated alternately for 4 cycles. After consolidation therapy, allogeneic stem cell transplantation (allo-SCT) was recommended if a suitable stem cell donor was identified. Those ineligible for allo-SCT, due to the lack of a suitable donor and/or comorbidity, received maintenance therapy comprising VCR, PSL and imatinib for 2 years from the date they achieved CR. Seventy patients were enrolled between October 2008 and December 2010. Of these, two patients were excluded because they were diagnosed with chronic myeloid leukemia blast phase. Therefore, 68 patients newly diagnosed with BCR–ABL positive ALL were included in this study. The median age was 49 years (18–64 years) and 41% were >54 years. Results: With this treatment regimen, 65 patients achieved CR (95.6%) and only 1% of them relapsed within 100 days after CR. Finally, 35/40 patients (81%) <55 years-old="" and="" 8="" 28="" 19="">54 years-old were able to receive allo-SCT in their first CR (13 from a sibling donor, 23 from an unrelated bone marrow donor, and 7 from unrelated cord blood). The 3-year OS and disease-free survival (DFS) rates were estimated at 62% and 52%, respectively. Three early deaths occurred during the induction course. One patient (51 years) died of pulmonary bleeding on day 9, another patient (59 years) died of sepsis on day 15, and the third patient (62 years) died of cerebral hemorrhage on day 15. Grade 3 or 4 non-hematologic adverse events including febrile neutropenia and liver dysfunction was reported in 60.3% and 11.8% of the patients, respectively. Twelve patients relapsed after achieving CR with a median time of 307 (64–1053) days. Moreover, 6/43 patients who received allo-SCT relapsed with a median time of 346 (149–602) days. The probability of DFS at 3 years was 72% for patients who underwent allo-SCT in CR compared to only 21% for patients without allo-SCT (p = 0.0004)(Figure.1). Conclusion: We conclude that imatinib-based chemotherapy produced a very high CR rate, thus allowing a high proportion of patients to prepare for allo-SCT, particularly patients 55 years. Moreover, the intensified consolidation therapy reduced the rate of early relapse after induction therapy and resulted in a higher rate of DFS after allo-SCT. Figure 1 Figure 1. Disclosures Hatta: Bristol Myers Squibb: Honoraria. Miyazaki:Novartis: Honoraria. Ohnishi:Novartis: Honoraria.
36
Wickerson, Lisa, Denise Helm, Chaya Gottesman, Dmitry Rozenberg, Lianne G. Singer, Shaf Keshavjee, and Aman Sidhu. "Telerehabilitation for Lung Transplant Candidates and Recipients During the COVID-19 Pandemic: Program Evaluation." JMIR mHealth and uHealth 9, no. 6 (June 17, 2021): e28708. http://dx.doi.org/10.2196/28708.
Full textAbstract:
Background The COVID-19 pandemic resulted in a rapid shift from center-based rehabilitation to telerehabilitation for chronic respiratory disease and lung transplantation due to infection control precautions. Clinical experience with this delivery model on a large scale has not been described. Objective The aim of this study is to describe usage and satisfaction of providers and lung transplant (LTx) candidates and recipients and functional outcomes following the broad implementation of telerehabilitation with remote patient monitoring during the first wave of the COVID-19 pandemic. Methods This study was a program evaluation of providers, LTx candidates, and early LTx recipients who used a web-based, remote monitoring app for at least four weeks between March 16 and September 1, 2020, to participate in telerehabilitation. Within-subjects analysis was performed for physical activity, Self-efficacy For Exercise (SEE) scale score, aerobic and resistance exercise volumes, 6-minute walk test results, and Short Physical Performance Battery (SPPB) results. Results In total, 78 LTx candidates and 33 recipients were included (57 [51%] males, mean age 58 [SD 12] years, 58 [52%] with interstitial lung disease, 34 [31%] with chronic obstructive pulmonary disease). A total of 50 (64%) LTx candidates and 17 (51%) LTx recipients entered ≥10 prescribed exercise sessions into the app during the study time frame. In addition, 35/42 (83%) candidates agreed the app helped prepare them for surgery and 18/21 (85%) recipients found the app helpful in their self-recovery. The strongest barrier perceived by physiotherapists delivering the telerehabilitation was patient access to home exercise and monitoring equipment. Between the time of app registration and ≥4 weeks on the waiting list, 26 LTx candidates used a treadmill, with sessions increasing in mean duration (from 16 to 22 minutes, P=.002) but not speed (from 1.7 to 1.75 mph, P=.31). Quadriceps weight (pounds) for leg extension did not change (median 3.5, IQR 2.4-5 versus median 4.3, IQR 3-5; P=.08; n=37). On the Rapid Assessment of Physical Activity questionnaire (RAPA), 57% of LTx candidates scored as active, which improved to 87% (P=.02; n=23). There was a decrease in pretransplant 6-minute walk distance (6MWD) from 346 (SD 84) meters to 307 (SD 85) meters (P=.002; n=45) and no change in the SPPB result (12 [IQR 9.5-12] versus 12 [IQR 10-12]; P=.90; n=42). A total of 9 LTx recipients used a treadmill that increased in speed (from 1.9 to 2.7 mph; P=.003) between hospital discharge and three months posttransplant. Quadriceps weight increased (3 [IQR 0-3] pounds versus 5 [IQR 3.8-6.5] pounds; P<.001; n=15). At three months posttransplant, 76% of LTx recipients scored as active (n=17), with a high total SEE score of 74 (SD 11; n=12). In addition, three months posttransplant, 6MWD was 62% (SD 18%) predicted (n=8). Conclusions We were able to provide telerehabilitation despite challenges around exercise equipment. This early experience will inform the development of a robust and equitable telerehabilitation model beyond the COVID-19 pandemic.
37
Pascal, Laurent, Odile Beyne Rauzy, Sabine Brechignac, Dominique Vassilieff, Olivier Ernst, Céline Berthon, Emmanuel Gyan, Francois Dreyfus, Pierre Fenaux, and Christian Rose. "Highly Transfused MDS Patients Often Have Cardiac Iron Overload, as Shown by MRI Assessment." Blood 116, no. 21 (November 19, 2010): 2906. http://dx.doi.org/10.1182/blood.v116.21.2906.2906.
Full textAbstract:
Abstract Abstract 2906 Background: Cardiac complications of transfusional iron overload are well documented in various inherited anemias. In regularly transfused MDS, the deleterious role of iron overload on cardiac disease is more disputed, due in particular to frequent concomitant causes of cardiac failure. Cardiac MRI T2* allows accurate and specific measurement of iron content. Methods: We prospectively evaluated in 4 centers of the GFM by standardized and transferable MRI methods both cardiac T2* according to Anderson (Eur Heart J. 2001Dec;22(23):2171-9) and liver iron content (LIC) according to Gandon (Lancet. 2004 Jan 31;363(9406):357-62), as well as cardiac function by routine echocardiography or MRI in regularly transfused MDS patients. Results: From Dec 2005 to March 2010, 73 patients (pts) were included (14 of them had more than one MRI evaluation over time): 38 M/35F, Median age 68 (24-86); WHO : RA=5, RARS=33, RMCD-RS=3, RMCD=1, RAEB1=9, RAEB2=5, RAEB-T/AML=1, 5q- syndrome=8 and unclassified=8; Karyotype: fav n=50, Int n=9, unfav n=4, failure n=10; IPSS: low n=29, Int-1 n=28, Int-2 n=5 and High n=1, unknown n=10. Median interval from MDS diagnosis and MRI T2* assessment was 49 months (range 0–324). Median serum ferritin at MRI assessment was 1750 ng/ml (range 282–7339) and 54/73 pts were on chelation therapy (CT) (median duration of CT prior to first MRI: 18 months, range 1–125). 37/73 pts had cardiac symptoms and 28 were on cardiac therapy. At first MRI T2* analysis, the median number of RBC units transfused was 68 (range 5–574). Median LIC was 330 micromoles/g/dw (range 40–908). Median Cardiac T2* was 27 ms (range 6–74). 14/73 pts had cardiac iron overload defined by MRI T2* ≤20 ms (19%) and among them 3/73 (4%) had severe cardiac iron overload (T2*≤ 10 ms). LVEF was below normal (55%) in 13/59 cases evaluated. A correlation was found between cardiac T2*and the number of RBC units transfused (Pearson correlation =-0.342, p=0.004) but not with LIC (p= 0.65) and serum ferritin (p=0.21). Cardiac overload was seen in 1/19 (5.5%) pts transfused <50 RBC units, 4/37(12.1%) pts transfused 50–150 units, 9/17 (52.9%) pts transfused >150 units (p= 0.0005). Those 3 pt subgroups also differed in median LIC (μmoles/g/dw) (<50 units= 250, 50–150 units=340, > 150 units=414) (p=0.044 Kruskall-Wallis' test), but not significantly in serum ferritin (p= 0.085). No significant correlation was found between decreased LVEF (< 55%) and cardiac T2* <20 ms (p=0.5), or T2*≤10 ms (p=0.23). In particular, 5/13 pts (38%) with LVEF <55% had T2*<20ms, vs versus 8/46 pts (17%) with LVEF >55% (p= 0.13). However, 1/14, 0/30 and 3/12 pts having received <50, 50–150 and > 150 RBC units had severe cardiac failure (ie LVEF≤35%)(p=0.012). 3/4 pts with severe cardiac failure had T2*< 20ms,compared to 8/54 pts without severe cardiac failure (p=0.023). 14 pts had another cardiac MRI 6 to 34 months (median 18) after the first. All were on CT and had received a median of 60 and 214 PRBC units at first and last MRI, resp. Median Cardiac T2* was 21.6 ms (range 8.5–35.3) and. 28 ms (range 6.4–41) at last and at first assessment, respectively (p=0.3) Conclusions: Moderate and severe post transfusional cardiac iron overload was seen in 19% and 4% of regularly transfused MDS, respectively. The level of cardiac iron overload was well correlated to the number of RBC transfused. The impact of cardiac overload on LVEF was unclear except in pts with severe cardiac impairment (LVEF <35%), possibly suggesting that iron overload is only one of the factors responsible for cardiac disease in many of those elderly patients. Disclosures: No relevant conflicts of interest to declare.
38
Bayle, Arnaud, Florent Peyraud, Laila Belcaid, Maxime Brunet, Miha Aldea, Rebecca Clodion, Paul Dubos, et al. "Abstract 3414: Systematic comparison of ctDNA vs tissue sequencing with a large panel to guide therapy in patients with advanced cancer: A study from the French National Center for Precision Medicine (PRISM)." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3414. http://dx.doi.org/10.1158/1538-7445.am2022-3414.
Full textAbstract:
Abstract Background: Genomic profiling with tissue sequencing is still considered as the gold standard despite several limitations including screening failures due to limited tissue availability, and inability to capture intratumor spatial and temporal heterogeneity, which may impair accurate treatment selection. Several studies have demonstrated the potential of circulating tumor DNA (ctDNA) to detect genomic alterations at high accuracy compared with tissue analysis. However, no studies have comprehensively evaluated differences between tissue and ctDNA by using a large panel in the same cohort. Methods: Genomic analysis was performed for each patient by using the Foundation One Liquid CDx Assay and the Foundation One CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability). Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were defined by the MTB according to the existing level of evidence (ESCAT tiers) and molecular-based treatment suggestions were proposed where possible. Results: Between Dec 2020 and Nov 2021, 1021 patients (median age: 62 years) with advanced cancer underwent both tissue and ctDNA NGS. Five most frequent tumor types were colorectal (N=137,13%), NSCLC (N=130,13%), breast (N=120, 12%), prostate (N=82, 8%) and pancreas (N=65, 6%). Median time elapsed between request and assay results was 12 days for ctDNA and 46 days for tissue. Testing failure was 15% for tissue and 3.9% for ctDNA. Overall, 824 (81%) patients had evaluable results for both tissue and liquid. Total number of cancer-related alterations and variants of unknown significance were 4704 and 11673 vs 4645 and 7481 for ctDNA and tissue, respectively. Proportion of patients with a higher number of cancer alterations identified in ctDNA compared with tissue increased in parallel with the time elapsed between the tissue and ctDNA sampling (45% vs 33% for a delay > 26 months or < 8 months). MSI and TMB status were concordant for 71% and 64% of patients, respectively. MSI status was evaluable for 97% of patients through ctDNA vs 90% through tissue. Number of actionable alterations was similar in 346 (42%) of cases, whereas it was higher in tissue for 289 (35%) and in liquid for 189 (23%) patients. ctDNA profiling allowed the identification of an ESCAT I/II or III or IV alteration not present in tissue for 74 (9%), 113 (14%) and 52 (6%) patients, respectively. Overall, MTB recommended a matched therapy for 430 patients (52%). Such a recommendation would not have been made without the results of ctDNA for 120 patients (15%). Conclusion: This systematic comparison of ctDNA vs tissue sequencing demonstrates the capacity of ctDNA for capturing clinically relevant alterations to guide therapy in cancer patients with high accuracy and rapid turnover results. Citation Format: Arnaud Bayle, Florent Peyraud, Laila Belcaid, Maxime Brunet, Miha Aldea, Rebecca Clodion, Paul Dubos, Damien Vasseur, Claudio Nicottra, Santiago Ponce, Isabelle Soubeyran, Emmanuel Khalifa, Yohann Loriot, Benjamin Besse, Ludovic Lacroix, Etienne Rouleau, Geoffrey Oxnard, Fabrice Barlesi, Fabrice Andre, Antoine Italiano. Systematic comparison of ctDNA vs tissue sequencing with a large panel to guide therapy in patients with advanced cancer: A study from the French National Center for Precision Medicine (PRISM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3414.
39
Khouja, Mouhamad, Anke Schilhabel, Michaela Kotrova, Monika Brüggemann, Christian Kuffer, Derek Blair, Nikos Darzentas, and Christiane Pott. "Disease Kinetics Measured By Circulating Tumor DNA Correlates with Treatment Response after Tafasitamab in Combination with R-CHOP with or without Lenalidomide in First Line Treatment of DLBCL." Blood 138, Supplement 1 (November 5, 2021): 3498. http://dx.doi.org/10.1182/blood-2021-153176.
Full textAbstract:
Abstract Background Currently available clinical and biological prognostic factors do not adequately identify first-line DLBCL patients at risk for treatment failure. In DLBCL, circulating tumor DNA (ctDNA) can be utilized as a for molecular disease classification, detect minimal residual disease (MRD) or predict disease progression. We hypothesized that ctDNA detected by the EuroClonality immunoglobulin-based next generation sequencing (IG-NGS) assay correlates with treatment response and outcome. Patients and methods Overall, 451 samples (41 diagnostic fresh frozen paraffin embedded (FFPE) biopsies, 64 peripheral blood mononuclear cells (PBMC) and 346 plasma samples) from patients from a Phase Ib study in de novo DLBCL treated with tafasitamab and R-CHOP or tafasitamab and R-CHOP in combination with Lenalidomide (First-MIND; MOR208C107) were analyzed. DNA from FFPE or diagnostic PBMC was sequenced by using a 2-step PCR approach with the Euroclonality NGS IGH-VJ, IGH-DJ and IGK primer sets (euroclonality.org) (Brüggemann, Leukemia, 2019) with a number of primers adapted for usage in short fragment cfDNA. IG markers were identified at abundance level ≥5% of annotated IG reads and a >1 log higher abundance to the next most frequent clonotype. Disease related clonotypes were traced in plasma during (C2D1 and C4D1 n=34) and at end of treatment (EOT n=32) by a 1-step PCR approach and sequencing of at least 5000 human genome equivalents (hGE) of cell free (cf)DNA. ctDNA levels were determined as the number of specific clonotype molecules per input genome equivalents normalized by a reference standard DNA spiked into each sample as cIT-QC (Knecht, Leukemia, 2019) and reported per plasma volume. Data were analysed by ARResT/Interrogate (Bystry, Bioinformatics, 2017). Patients were reported MRD positive if ≥1 clonal IG rearrangement was detected. Results From 41 patients with available diagnostic FFPE and sufficient DNA quality for marker screening, 34 (89%) had at least 1 detectable clonal marker (IGH-VJ, IGH-DJ or IGK). One clonal IG marker was identified in 20/34 (59%) patients, whereas two or three markers were identified in 9 (27%) and 5 (14%) patients, respectively. Disease specific clonotypes identified in FFPE were recovered in 11/34 PBMC samples (32%) with a median abundance of 0,29% (range 0.006-21.9%) demonstrating a peripheral blood involvement. In 32/33 (97%) pretreatment plasma samples, ctDNA was detected with a median copy number of 172.5/ml plasma. cfDNA and ctDNA levels prior to treatment correlated with IPI and LDH (Fig1). ctDNA dynamics during treatment demonstrated rapid treatment response at C2D1. 23/34 samples were either MRD neg (n=19) or showed a ctDNA reduction ≥ 2 log levels (Fig2). At C4D1 7/34 (20%) samples had low-level detectable MRD and at EOT 29/32 (91%) patients achieved MRD negativity after treatment with tafasitamab and R-CHOP +/- lenalidomide (LOD 2 x 10 -4 for follow-up samples). Early ctDNA dynamics predicted metabolic response when applying a threshold of ctDNA reduction to <1% after the first treatment cycle. 25/28 (89%) patients completing treatment and achieving PET-response could be identified early during treatment by ctDNA assessment. Conclusion Baseline ctDNA levels determined by the EuroClonality IG-NGS assay and absolute cfDNA amounts correlated with pre-treatment risk factors. ctDNA dynamics after the 1 st treatment cycle demonstrated rapid treatment response to tafasitamab + RCHOP +/- lenalidomide and correlated with metabolic response. Assessment of ctDNA dynamics allows early response assessment and might be useful for risk stratification in patients with DLBCL. Figure 1 Figure 1. Disclosures Kuffer: Morphosys AG: Current Employment. Blair: Morphosys AG: Current Employment.
40
Marin-Niebla, Ana, Eduardo Rios-Herranz, Jose F. Falantes, Mariluz Martino, Ildefonso Espigado, and Alvaro Urbano-Ispizua. "Incidence of Neutropenia and Hypogammaglobulinemia and Correlation with the Infections Rate in Indolent Non-Hodgkin Lymphoma (NHL) Receiving Rituximab Maintenance." Blood 110, no. 11 (November 16, 2007): 4495. http://dx.doi.org/10.1182/blood.v110.11.4495.4495.
Full textAbstract:
Abstract Rituximab (R) maintenance has demonstrated a significant increase in both median PFS and OS in follicular lymphoma. However, such an effective strategy carries a concern about the long-term effects of rituximab on the immune system and the risk of infectious complications. In fact, neutropenia, and less frequently, hypogammaglobulinemia, occur with rituximab treatment, but this is still a scarcely explored issue. We analyzed our experience with R-maintenance in patients with indolent non-Hodgkin lymphoma (NHL) to evaluate the incidence of neutropenia and hypogammaglobulinemia, the type and incidence of infections and the factors associated with infection. Patients and Methods: Patients (pts) with indolent NHL in CR or PR after induction or salvage treatment (either with or without R), receiving R maintenance (R= 375 mg/m2; 2 schedules: 4 weekly doses every 6 months (4/6) in high-risk patients and 1 dose every 3 months (1/3) in low-risk. Total duration= 2 years) from June 2003 to June 2007. We examined the following variables for correlation with the incidence of infection: number and type of previous treatments (with/without R, with/without fludarabine), previous splenectomy and/or radiotherapy, response to previous treatments before R-maintenance, and R-maintenance schedule used. Results: Forty-seven pts (age (Mean[R]): 57[34–76]; gender F26:M21) with indolent NHL [FL 27 (57.4%), MCL 2 (4.3%), MZL 7 (14.9%), LPL/Waldestrom 5 (10.6%), MALT 6 (12.8%)] were retrospectively evaluated. At diagnosis: ECOG 0–1: 29 (61.7%), 2–3: 6 (12.8%); stage III–IV 43 (91.5%); B-symptoms 23 (48.9%); FLIPI 0–2: 56.4%, 3–5: 43.6%. Marrow involvement 34 (72.3%), splenomegaly 14 (29.8%) and hepatomegaly 5 (10.5%). LDH (Mean[R]): 346 [115–854], b2–microglobulin: 3.17 [1.3–7.9], Neutrophil count (x 109/L): 8.89 [0.14–31.6], IgG: 1044.8 [214–2080], IgA: 186.8 [35–570], IgM: 532.3 [17–6670]. Number of treatments before R-maintenance (M[R]): 1 [1–3]. Thirty-eight (80.9%) pts had received R-containing therapy and 43 (91.5%) fludarabine-containing regimens. Forty (85.1%) had achieved CR and 7 (15.2%) PR. Follow-up from diagnosis (Mean[R]): 35.4 months [8–116]; follow-up from start of R-maintenance: 16.8 months [1–53]. After R-maintenance, 9 pts (19.1%) presented neutropenia grade 3–4. The presence of splenomegaly (p=0.03) and hepatomegaly (p=0.03) at diagnosis significantly correlated with neutropenia 3–4. No relationship was found with the maintenance schedule used (4/6 vs 1/3), previous R or fludarabine, or with the number of previous treatments. Incidence of hypogammaglobulinemia was (*data available from 33 pts): IgG<500: 8 (24.2%), IgA<60: 10 (30.3%), IgM<50: 13 (39.4%). Infections recorded in the 47 pts: recurring gastroenteritis 1 patient, HZV 2 pts, ORL infections 1 patient, and 2 cases of severe pulmonary infections requiring hospitalization. A significant correlation was found between infection and IgG<500 (p=0.04) and with neutropenia 3–4 (p=0.03). Conclusions: Rituximab maintenance is a safe strategy with a low incidence of infectious complications. Although severe neutropenia and hypogammaglobulinemia are not rare side effects of prolongued R treatment, only 2 patients presented severe infectious complications in our cohort. The only factors significantly influencing the incidence of infection were neutropenia 3–4 and low levels of IgG. No differences were observed between both schedules of R-maintenance regarding the infections rate.
41
Forconi, Francesco, Emanuele Cencini, Davide Rossi, Riccardo Bomben, Elisa Sozzi, Marta Coscia, Massimo Massaia, et al. "Unmutated IGHV1-69/D3-16/J3 Stereotyped HCDR3 Rearrangements (Subset 6) Are Associated with Indolent Disease Course and Have Outcome Independent of Mutational Status In Early Stage CLL (Rai 0)." Blood 116, no. 21 (November 19, 2010): 1371. http://dx.doi.org/10.1182/blood.v116.21.1371.1371.
Full textAbstract:
Abstract Abstract 1371 Background: IGHV1-69 gene identifies the most frequent IGHV gene in chronic lymphocytic leukemia (CLL) and identifies the paradigm of unmutated CLL (U-CLL), being used in roughly 1/3 U-CLL. It is often rearranged to form subsets of stereotyped HCDR3 patterns, likely selected and transformed from the natural naïve B-cell repertoire (Blood. 2010; 115:71-7). Being unmutated, IGHV1-69 CLL are hypothetically expected to have competent tumor B-cell receptors (BCR) and to progress more rapidly. However, it has not been investigated if progression occurs similarly in all the subsets. Aims: we aimed to investigate the prognostic significance of mutational status and of stereotypic B-cell receptors in IGHV1-69+ CLL. Methods: Nucleotide sequences of the tumor IGHV1-69/D/J rearrangement, clinical and molecular prognostic parameters at diagnosis and clinical status at follow-up of 294 IGHV1-69+ CLL patients were obtained from 22 hematological Institutions in Italy. CLL B-cell derived IGHV1-69 rearrangements were scanned for HCDR3 stereotypic patterns and assigned to subsets according to the criteria by Murray et al (Blood. 2008; 111: 1524–1533). Enpoint of outcome was time to progression requiring first treatment according to NCI criteria (TTFT) in Rai stage 0 CLL. Results: Of 294 IGHV1-69+ CLL, 264 (89,8%) were unmutated, 168 (57,1%) were assigned to subsets, of which subsets 7 (n=23, 7,8%), 6 (17, 5,8%), 3 (13, 4,4%), 5 (10, 3,4%) and 9 (10, 3,4%) were the most frequent. CD38, ZAP70, normal or sole del13, +12, del11 and del17p scored positive in 109/264 (58,7%), 139/245 (56,7%), 128/248 (50,5%), 51/248 (20,6%), 43/248 (17,3%) and 34/248 (13,7%). CLLs were reclassified as 18 (6,1%) clinical MBL, 101 (34,4%) Rai 0, 155 (52,7%) Rai I-II and 20 (6,8%) Rai III-IV CLL. Subset 6 was also UM in 16/17 (94,1%) cases. Prevalence of CD38 (p<.001), ZAP70 (p=.016), normal or sole del13 (p<.001), +12 (p=.026), del11 (p=.011), and clinical high risk CLL (p=.025) were lower in IGHV1-69 M-CLL than in IGHV1-69 U-CLL. TTFT was significantly shorter in stage 0 IGHV1-69 U-CLL than in IGHV1-69 M-CLL (49 vs 144 months, p<.001, while it was not different between CLL assigned or not to subsets (65 vs 55 months, p=.346). However, specific analysis of individual subsets revealed differential outcomes (p=.005). Among all, it emerged that subset 6 had a TTFT equivalent to IGHV1-69 M-CLL (p=.29) and significantly longer than stage 0 IGHV1-69 U-CLL (median not reached vs 48 months, p=.017). Conclusions: our analysis documents and confirms that unmutated status of IGHV, and not stereotypy, is a relevant prognosticator of outcome (TTFT) in CLL. In the IGHV1-69 CLL it exclude a role of IGHV gene use for CLL progression. However, the good prognosis of Rai 0 U-CLL assigned to subset 6 suggests a differential clinical benign course of this particular subset, irrelevant of unmutated status. One possibility is that the IGHV1-69/D3-16/J3 rearrangements of subset 6 produce a tumor-specific BCR with stereotypic HCDR3 patterns that are anergized by antigen while circulating in the peripheral blood in early stage (Rai 0) CLL. Disclosures: No relevant conflicts of interest to declare.
42
Edwards, M. J. "Julius Africanus und die christliche Weltchronik. Julius Africanus und die christliche Weltchronistik. Edited by Martin Wallraff. (Berlin-Brandenburgische Akademie der Wissenschaften. Texte und Untersuchungen zur Geschichte der altchristlichen Literatur. Archiv für die Ausgabe der Griechischen Christlichen Schriftsteller der ersten Jahrhunderte, 157.) Pp. viii+346 incl. 23 figs. Berlin–New York: Walter de Gruyter, 2006. €98. 13 978 3 11 019105 9; 10 3 11 019105 9." Journal of Ecclesiastical History 59, no. 1 (January 2008): 87–88. http://dx.doi.org/10.1017/s0022046907003405.
Full text
43
Phipps, Colin, Michael L. Linenberger, Damian J. Green, M. Corinna Palanca-Wessels, Pamela S. Becker, Laura S. Connelly-Smith, Nicholas Burwick, et al. "Cost and Utilization Of Stored Autologous PBSC To Support Tandem ASCT In MM Patients In The Era Of Novel Agent Therapy." Blood 122, no. 21 (November 15, 2013): 4507. http://dx.doi.org/10.1182/blood.v122.21.4507.4507.
Full textAbstract:
Introduction Historically, autologous stem cell transplantation (ASCT) for multiple myeloma (MM) improves overall survival (OS) compared to conventional chemotherapy alone. Before the introduction of novel agent therapy, tandem ASCT, defined as a second ASCT within 180 days of the first, was an important option for suboptimal responses after an initial ASCT and thus collecting adequate peripheral blood stem cells (PBSCs) for 2 transplants has been considered standard of care. However, the role of tandem transplants is being challenged by novel agent maintenance strategies. Considering this changing landscape of MM therapy, we sought to evaluate the current PBSC collection and storage practices that set the CD34+ cell dose goal to be sufficient for 2 transplants. Methods We obtained clinical, PBSC collection and storage data on MM patients who underwent ASCT from 1993 to 2011 from the Autologous Transplant and Cellular Therapy Laboratory databases at the Fred Hutchinson Cancer Research Center. We determined frequencies and trends of all second ASCTs, including tandem, costs involved in PBSC collection, storage, and utilization of the product that remained cryopreserved for a second ASCT. Cell dose target at our center is 5 x 106 CD34+ cells/kg/transplant. To analyze trends over time, we divided the sample into groups of 3 or 4 year periods. Collection and cryopreservation costs for second ASCT were calculated by first determining the number of days required to collect sufficient PBSC for one ASCT, then the number of additional days to complete the actual collection, and the cumulative costs of long-term storage in our facility. Cost was estimated per July 2012 charges: 1 day PBSC collection $3,016, 1 day processing for cryopreservation $5,955, 1 year storage fees $408 ($34/month). The cost of mobilization chemotherapy and growth factors were not included. Results From May 1993 to June 2011, 889 MM patients underwent PBSC collection and ASCT (111 of 1000 excluded due to incomplete records). Median total PBSC collection days was 2 (range 1 – 10) with median yield of 13.18 x 106/kg CD34+ cells. Median days to collect sufficient cells for one ASCT was 1 day (1 – 9) and 383 patients collected adequate cells for 2 ASCTs after 1 apheresis procedure. Of 889 patients, 135 underwent a second ASCT within a median 14 months (2.5 – 113) of the first. Number of second ASCTs per time period: 1993 to 1995 – 9 of 39 MM patients undergoing ASCT (23%), 1996 to 1999 – 18 of 100 (18%), 2000 to 2003 – 15 of 162 (9%), 2004 to 2007 – 62 of 251 (25%), 2008 to 2011 – 31 of 337 (9%). Fifty patients underwent tandem ASCTs and these accounted for 89%, 72%, 7%, 24%, and 42% of all second ASCTs during the respective periods; the other 85 occurred > 6 months after the first. Number of additional days and associated costs to collect and store PBSC for a second ASCT: 5 days ($44,855), n=1 patient; 4 days ($35,844), n=2; 3 days ($26,913), n=10; 2 days ($17,942), n=41; and 1 day ($8,971), n=211. 637 patients had unused PBSC that remained in storage for ≥ 1 year, with a rising trend over time: 1993 to 1995 – 7 (1%), 1996 to 1999 – 65 (10%), 2000 to 2003 – 77 (12%), 2004 to 2007 – 185 (29%), 2008 to 2011 – 303 (48%). Duration of storage was < 2 years for 34, 2 to 5 years for 346, and > 5 years for 257 patients. Median PBSC storage time was 40 months. PBSC products from 260 patients were discarded (or sent to repository), after a median storage of 54 months, for the following reasons: 5 had allogeneic transplant, 74 were alive and possibly concerned about costs and/or the unlikely need for a second ASCT, 3 had cell viability issues, and 178 patients had died. From January 2009, some patients received plerixafor to achieve the collection goal for 1 ASCT. Its cost was not considered additional. Estimated average cost for PBSC collection, cryopreservation and storage was at least $20,065.96/person and at least $6718.11/person was spent to collect and store PBSC for a tandem ASCT that was never performed. Conclusions Approximately 70% of patients had PBSC products that remained unused and in prolonged cryopreservation after the first ASCT. Estimated cost for collection and storage of PBSC beyond that needed for a single ASCT accounted for roughly 1/3 of total costs. This conventional practice should be reconsidered in view of rising treatment costs, the evolving role of novel agents in maintenance therapy, and the deeper responses achievable with novel agents prior to first ASCT, thus reducing the need for tandem ASCT. Disclosures: No relevant conflicts of interest to declare.
44
Сараев, Владимир Васильевич, and Фатима Тасымовна Кожегулова. "О СПОСОБАХ ОБОГРЕВА ДРЕВНИХ ЗЕМЛЯНОК В ПРЕДГОРНОЙ И ГОРНОЙ ЗОНЕ ИЛЕЙСКОГО АЛАТАУ." Kazakhstan Archeology, no. 1 (March 20, 2019): 28–42. http://dx.doi.org/10.52967/akz2019.1.3.28.42.
Full textAbstract:
Настоящая работа посвящена реконструкции способа обогрева жилища-землянки и возможным вариантам функционального назначения таких помещений в хозяйственно-бытовых традициях древнего населения Илейского Алатау. В 2018 г. авторами проводились исследования древних поселений в устье ущелья Узын-Каргалы, которые позволяют реконструировать хозяйственную структуру населения данного микрорайона. Была расчищена землянка в долине ручья Кайнарбулак, в конструкции которой отсутствовал очаг для обогрева помещения. В домостроительстве древних скотоводов горной зоны региона существовала традиция сооружения малогабаритных землянок с системой внешнего обогрева каменных стен. Пристенный очаг с дымоходом позволяет сохранить положительные факторы (быстрый обогрев, малый расход топлива) помещения небольшого объема и увеличивает полезную площадь в пользу обитателей. Данные помещения могли использоваться как для проживания, так и в хозяйственных целях, например, в качестве коптильни. Хронологические параметры возникновения подобной традиции по материалам комплекса древних стоянок скотоводов в долине ручья Кайнарбулак позволяют отнести ее к усуньскому периоду раннего железного века.
Библиографические ссылки
1. Аванесова Н.А. Культура пастушеских племен эпохи бронзы азиатской части СССР (по металлическим изделиям). Ташкент: «Фан» УзССР, 1991. 200 с.
2. Бернштам А.Н. Золотая диадема из шаманского погребения на р. Карагалинке // КСИИМК. 1940. Вып. 5. С. 23-31.
3. Бернштам А.Н. Историко-археологические очерки Центрального Тянь-Шаня и Памиро-Алтая // МИА СССР. 1952. № 26. 346 с.
4. Вайнштейн С.И. Мир кочевников центра Азии. М.: Наука, 1991. 296 с.
5. Валиханов Ч.Ч. Тенкри (бог) // Собр. соч. в 5 т. Алма-Ата: Главная ред. Казахской советской энциклопедии, 1984. Т. 1. С. 208-215.
6. Горячев А.А., Мотов Ю.А. Археологический комплекс Бутакты-I. Алматы: ТОО «KazBookTrade», 2018. 264с.
7. Горячев А.А., Потапов С.А. К вопросу о реконструкции жилища эпохи бронзы поселения Талапты-I // Казахское ханство в потоке истории: сб. матер. междунар. научн. конф., посвящ. 550-летию Казахского ханства. Алматы: Институт археологииим. А.Х. Маргулана, 2015. С. 342-351.
8. Горячев А.А., Сараев В.В. К вопросу о хозяйственно-культурном развитии древнего населения Алматы // Известия НАН РК. Сер. обществ. и гум. наук. 2015. № 6 (304). С. 5-18.
9. Горячев А.А., Чернов М.А. Орудия кожевенного ремесла и ткачества из археологического комплекса Тургень-II // История и археология Семиречья. Алматы: ОФ «Родничок», 2007. Вып. 3. С. 106-119.
10. Горячев А.А., Чернов М.А. Металлический инвентарь из погребальных комплексов эпохи бронзы Жетысу // Известия НАН РК. Сер. обществ. и гум. наук. 2017. № 1 (311). С. 5-24.
11. Итина М.А. История степных племен Южного Приаралья во II тыс. до н.э. М.: Наука, 1977. ТХАЭЭ. Т. 10. 240 с.
12. Кузьмина Е.Е. Металлические изделия энеолита и бронзового века Средней Азии. М.: Наука, 1966. 139 с.
13. Кузьмина Е.Е. Гончарное производство у племен андроновской культурной общности // Восточный Туркестан и Средняя Азия в системе культур древнего и средневекового Востока. М.: Гл. ред. восточн. лит. изд-ва «Наука», 1986. С. 152-182.
14. Кузьмина Е.Е. Откуда пришли индоарии? Материальная культура племен андроновской общности и происхождение индоиранцев. М.: МГП «Калина» ВИНИТИ РАН, 1994. 464 с.
15. Марьяшев А.Н, Горячев А.А. Поселения эпохи бронзы в верховьях ущелья Тургень и на плато Асы // История и археология Семиречья. Алматы: ОФ «Родничок», 2001. Вып. 2. С. 112-123.
16. Сараев В.В. Перспектива выявления фактов развитого оросительного земледелия в предгорьях Семиречья // Роль номадов в формировании культурного наследия Казахстана: научн. чтения памяти Н.Э. Масанова: сб. матер. междунар. научн. конф. Алматы: Print-S, 2010. С. 82-88.
17. Сараев В.В. Каргалинский древний историко-географический микрорайон // История и археология Семиречья. Алматы, 2017. Вып. 5. С. 68-90.
18. Сараев В.В., Горячев А.А. Шамсунский клад эпохи поздней бронзы у северных склонов Заилийского Алатау // Известия НАН РК. Сер. обществ. наук. 2011. № 3. С. 37-47.
19. Свод памятников истории и культуры Республики Казахстан. Алматинская область. Алматы: Агентство «Маматай», 2009. 106 с.
45
Kern, Wolfgang, Torsten Haferlach, Susanne Schnittger, and Claudia Haferlach. "Correlation Between Cytogenetic Aberrations Detected by Conventional Chromosome Banding Analysis and Specific Immunophenotypes in Patients with B-Cell Lymphoproliferative Diseases." Blood 112, no. 11 (November 16, 2008): 2544. http://dx.doi.org/10.1182/blood.v112.11.2544.2544.
Full textAbstract:
Abstract While typical cytogenetic aberrations and immunophenotypes, respectively, have been identified in distinct entities of B-cell lymphoproliferative diseases (B-LPD) their specificity is not complete in every case. Thus, the t(14;18), which is characteristic of follicular lymphoma, is present also in cases with other B-LPD. Furthermore, expression of CD5 can be observed in cases with B-LPD other than mantle cell lymphoma and chronic lymphocytic leukemia. Moreover, a variety of chromosome aberrations has been described which has not yet been assigned to distinct B-LPD subentities. Accordingly, immunophenotypes are not clear-cut for distinct B-LPD subentities but rather overlap with regard to some features, e.g. between marginal zone lymphoma and lymphoplasmacytic lymphoma. The aim of the present study therefore has been to characterize cases with B-LPD (excluding B-CLL) by conventional chromosome analysis and by multiparameter immunophenotyping and to assess whether and to which degree relations between the results of both methods exist. A total of 346 patients have been evaluated. The frequencies of the respective chromosomal aberrations were (more than one aberration occurred in some cases): t(8;14), 16 (4.6%); t(11;14) without additional aberrations, 10 (2.9%); t(11;14) with additional aberrations, 43 (12.4%); trisomy 12, 48 (13.9%); t(14;18), 18 (5.2%); t(14;19), 6 (1.7%); trisomy 3, 23 (6.6%); trisomy 8, 3 (0.9%); del7q, 9 (2.6%); del13q, 30 (8.7%); 17p-, 30 (8.7%); complex (≥3) aberrations, 58 (16.8%) while a normal karyotype was found in 126 (36.4%) cases. The comparison with immunophenotypes revealed various previously reported findings like the stronger expression of CD10 in cases with t(8;14) (33.4 vs. 14.6%, p=0.001) and of CD5 in cases with t(11;14) (73.3 vs. 48.4%, p<0.001). Furthermore, the respective chromosome aberrations were found to be associated with a significantly (p<0.05 for all comparisons) higher(+)/lower(−) expression of the following antigens: t(8;14), CD10+CD38+CD25+; t(14;18), CD10+CD11c−; t(11;14) with additional aberrations, CD38+CD20+CD22+CD5+CD 79b+FMC7+IgM+; t(11;14) without additional aberrations, CD22+; t(14;19), CD11c+; 17p−, CD38−CD22+CD79b+FMC7+CD11c+; trisomy 12, CD25+CD5+CD10−CD23+; del13q, CD25+CD20+CD22+CD5+CD79b+CD11c−; del7q, CD25−; complex aberrations, CD20+CD22+CD79b+; trisomy 8, CD5−. Accordingly, regarding the whole series distinct antigens were found coexpressed at high frequencies. Specifically, highly significant positive correlations (p<0.001, r>0.5) were found between CD20, CD22, CD79b, and FMC7. In contrast, the expression of CD10 was highly significantly negatively related (p<0.001, r<−0.2) to the expression of CD11c and CD5. Overall, however, there was no complete positive or negative correlation between any of the antigens analyzed with regard to their respective expression intensities. Hierarchical cluster analysis has been performed to assess correlations between the expression intensities of distinct antigens on the one hand and distinct chromosome aberrations on the other hand. While the majority of cases with t(11;14) clustered rather closely together, cases with other chromosome aberrations were distributed more heterogeneously. These data suggest that there are significant correlations between the expression intensities of specific antigens as well as between these expression intensities and distinct chromosome aberrations in B-LPD. However, the respective immunophenotype patterns were much more diverse and no strong correlations were found to most chromosome aberrations. Only in cases with t(11;14) or with t(8;14) strong correlations have been observed with highly significant differences in antigen expression as compared to cases with other cytogenetic aberrations. The data suggest that the biologic background in most B-LPD is heterogeneous from the diagnostic point of view which is in contrast to other and also genetically clearly defined hematologic malignancies such as CML or APL. To clarify the more diverse biology and its clinical significance also in conjunction with histologic findings further studies are warranted.
46
Minoda, S., R. Sada, S. Matsushita, Y. Nakayama, H. Akebo, Y. Tsugihashi, H. Ishimaru, and K. Hatta. "POS0516 REDEFINING THE CLINICAL AND LABORATORY FEATURES OF RHEUMATIC PLEURAL EFFUSION: A 30-CASE SERIES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 492.1–492. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1197.
Full textAbstract:
Background:Rheumatoid pleural effusion (RPE) is a common extra-articular complication in patients with rheumatoid arthritis (RA). Previous studies have shown that RPE usually occurs in middle-aged men with rheumatoid factor (RF)-positive RA. RPE usually has features of pleural fluid acidosis, high lactate dehydrogenase (LDH) levels, and very low glucose levels(1). However, to the best of our knowledge, these findings were based on very few case series and reports, and most of these reports were published by the early 2000s(1, 2).Objectives:To investigate the clinical and laboratory characteristics and typical clinical courses of patients with RPE in a single centre of Japan since the beginning of the 21st century.Methods:Medical records of RPE patients were retrospectively reviewed between May 2006 and September 2020. RPE was identified by fulfilling these five conditions: (1) confirmation of the RA diagnosis; (2) having an exudative pleural effusion according to Light’s criteria; (3) negative results of pleural fluid culture; (4) negative results of pleural fluid cytology; and (5) exclusion of a parapneumonic effusion or empyema defined as no antibiotic use or ineffectiveness of antibiotics during the clinical course. Patients were divided into two groups according to their age at diagnosis: <60 years (Group A) and ≥60 years (Group B).Results:A total of 30 cases of RPE were included in the study. The median age was 71 years (interquartile range [IQR], 66–78 years). Of these patients, 16 (53%) were women. The median disease duration of RA was 98 months (IQR, 8–162 months). The two groups comprised six patients aged <60 years old and 24 patients ≥60 years. The median age was 54 years (IQR, 49–56 years) in Group A and 74 years (IQR, 69–78 years) in Group B. The median disease duration of RA was longer in Group B than that in Group A (132 vs. 3 months, p=0.008). Compared with Group A, Group B had fewer patients with fever (14% vs. 83%, p=0.003), and had lower serum C-reactive protein levels (3.3 vs. 11.1 mg/dL, p=0.03). Moreover, Group B was more likely to show mild inflammatory pleural fluids with higher pH (7.5 vs. 7.2, p=0.005) and lower LDH levels (155 vs. 1810 IU/L, p=0.046). Corticosteroids were started or increased in five (83%) and nine (38%) patients, and biologic disease-modifying anti-rheumatic drugs were started in one (17%) and two (8%) patients in groups A and B, respectively. One patient (16%) died within 5-years in Group A, and seven patients (29%) died in Group B.Conclusion:In contrast to previous studies, RPE was seen in older patients as well as middle-aged adults, and the pleural fluid analysis in older patients with RPE showed milder inflammation than the middle-aged patients.References:[1]Balbir-Gurman A, et al. Semin Arthritis Rheum. 2006 Jun; 35(6): 368-78.[2]Faurschou P, et al. Thorax. 1985 May; 40(5): 371-5.Table 1.Comparison of clinical and laboratory findings between Group A and Group B.Group A (n=6)Group B (n=24)P valueAge (years)54 [49-56]74 [69-78]Female2 (n=6, 33.3)14 (n=24, 58.3)0.38Disease duration of RA (months)3 [1-9]132 [44-199]0.008Fever ≥37.0°C5 (n=6, 83.3)3 (n=22, 13.6)0.003SerumCRP (mg/dL)11.1 [5.6-1.4]3.3 [0.9-10.5]0.03 RF (IU/mL)100 [19-816]63 [23-193]0.95 Anti-CCP ab positive5 (n=6, 83.3)12 (n=15, 80)1.00Pleural fluid analysispH7.2 [7.2-7.2]7.5 [7.4-7.5]0.005LDH (IU/L)1810 [594-2932]155 [123-346]0.046Glu (mg/dL)59 [10-123]105 [91-122]0.42Tp (g/dL)5.1 [4.9-5.6]4.6 [3.6-5.2]0.21Number of cells (/μL)5235 [3353-9300]3300 [1490-5008]0.27 Glu/serum Glu0.41 [0.09-0.99]1.05 [0.85-1.15]0.71Started or increased CS5 (n=6, 83.3)9 (n=24, 37.5)0.18Started bDMARDs1 (n=6, 16.6)2 (n=24, 8.3)0.50Died within 5 years1 (n=6, 16.6)7 (n=24, 29.1)1.00Data are median [interquartile range], or number (total number, percent).Abbreviations: RA, rheumatoid arthritis; CRP, C-reactive protein; RF, rheumatoid factor; Anti-CCP ab, anti-cyclic citrullinated peptide antibodies; LDH, lactate dehydrogenase; Glu, glucose; Tp, total protein; CS, corticosteroid; bDMARDs, biologic disease-modifying anti-rheumatic drugsDisclosure of Interests:None declared
47
Tomiyama, Yoshiaki, Yoshitaka Miyakawa, Shinichiro Okamoto, Shinya Katsutani, Akiro Kimura, Yasushi Okoshi, Haruhiko Ninomiya, et al. "Six Month Treatment of Low Dose Eltrombopag Is Efficacious in Japanese Patients with Refractory Chronic Immune Thrombocytopenic Purpura (ITP)." Blood 114, no. 22 (November 20, 2009): 1324. http://dx.doi.org/10.1182/blood.v114.22.1324.1324.
Full textAbstract:
Abstract Abstract 1324 Poster Board I-346 INTRODUCTION Eltrombopag (PROMACTA®, GlaxoSmithKline) is the first non peptide, oral thrombopoietin receptor agonist which promotes the differentiation and proliferation of megakaryocytes and increases platelet counts. This study is a randomized study comprising a double-blind (DB), placebo (PBO)-controlled phase, followed by an open-label (OL) phase in previously treated Japanese patients with chronic ITP and platelet counts <30Gi/L. Since eltrombopag exposure has been reported to be 70% higher in East Asian patients with ITP as compared to Caucasian patients and given the chronic nature of the disease state, the lower initial dose of 12.5mg/day was used in this study. METHODS In the DB phase, patients were randomized into one of two treatment groups to receive either an initial dose of 12.5mg of eltrombopag or matching PBO once daily. A dose increase was allowed at Day 22 based on individual platelet count. For each patient, primary data up to Week 6 were frozen and the treatment assignment was unblinded at Week 7 before entering into the OL phase. The primary endpoint of the DB phase was to compare the proportion of patients achieving a platelet count of ≥50Gi/L and ≤400Gi/L after 6 weeks of eltrombopag or PBO. All patients completing the DB phase progressed to the OL phase. In the OL phase, patients who had received eltrombopag during the DB phase continued to receive eltrombopag for up to 26 weeks with dosage (12.5, 25 or 50mg/day) based on the individual platelet count. Patients who had received PBO during the DB phase initiated treatment with 12.5mg of eltrombopag and received eltrombopag for 26 weeks with dosage (12.5, 25 or 50mg/day) based on the individual platelet count. The primary efficacy endpoint of the long-term OL phase was to assess the ability of eltrombopag to elevate and maintain platelet counts in a target range (50-400Gi/L) during 6 months of treatment. Bleeding symptoms were also assessed subjectively and objectively at each visit. Blood samples were collected to describe the PK profile of eltrombopag. RESULTS Of 23 patients randomized, 16 had undergone splenectomy, 17 had received H. pylori eradication and 19 were receiving concomitant ITP medication at baseline. DB Phase: 23 patients were randomized to receive 6 weeks of once daily eltrombopag (n=15) or matching PBO (n=8). By Week 3, 5 of 15 (33.3%) patients receiving 12.5mg eltrombopag achieved platelet counts >50Gi/L. Three of the responders had platelet counts ≥100Gi/L at Week 3. At the end of the Week 6, 9 of the 15 patients (60.0%) receiving eltrombopag were responders (platelet count 50-400Gi/L). Three of these patients were receiving 12.5mg and the remaining 6 were receiving 25mg. All PBO patients failed to achieve a response at any point during the 6 weeks. Long-term OL Phase: During the first 3 weeks when all patients received 12.5mg of eltrombopag, 21.7% of patients achieved a platelet response of ≥50Gi/L. From Day 22 onwards a greater proportion of patients (47.8-69.6%) achieved platelet counts within the target range of 50-400Gi/L. Over the initial 3 week period a gradual rise in median platelet counts was observed and a marked increase in the median platelet count was observed from Day 22. From Day 36 until Week 26 the median platelet count was consistently within the target range of 50-400Gi/L. Eltrombopag therapy was associated with a consistent reduction in the proportion of patients with bleeding. 36.8% (7/19) had a reduction in concomitant ITP medication (corticosteroids) during the 6 months. Adverse events (AE) were reported in 22 out of 23 patients throughout the study. Nasopharyngitis was the most common AE (43%). One patient receiving eltrombopag developed a serious AE (transient ischemic attack of mild severity, considered related to study medication by the investigator) on day 10 and was withdrawn from the study. The AEs were mostly mild to moderate. There was a linear relationship between eltrombopag dose and exposure. CONCLUSION Six month treatment of low dose eltrombopag with an initial dose of 12.5mg up to a maximum dose of 50mg increased platelet counts and reduced bleeding and the use of concomitant ITP medication in Japanese patients with refractory ITP. The higher eltrombopag exposure in Japanese patients than in Caucasian patients may explain the equivalent efficacy at lower dosages of eltrombopag. Eltrombopag was well-tolerated and is an important new treatment option for patients with chronic ITP. Disclosures Miyakawa: GlaxoSmithKline: Consultancy; Nissan Chemical Industries: Research Funding; Shionogi: Honoraria; Ono Pharmaceutical: Honoraria. Ikeda:Daiichi-Sankyo: Research Funding; Tanabe-Mitsubishi: Research Funding; Chugai: Research Funding; Bayer: Research Funding; Daiichi-Sankyo: Honoraria; Bayer: Honoraria; Sanofi-Aventis: Honoraria; Takeda: Honoraria; GlaxoSmithKline: Honoraria; Kaken: Honoraria; Sumitomo: Honoraria; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Boehringer: Membership on an entity's Board of Directors or advisory committees. Koh:GlaxoSmithKline: Employment. Katsura:GlaxoSmithKline: Employment. Kanakura:GlaxoSmithKline: Consultancy; Kyowa Hakko Kirin: Research Funding; GlaxoSmithKline: Research Funding.
48
Pianko, Matthew J., Timothy Tiutan, Jessica Flynn, Sean M. Devlin, Insara Jaffer-Sathick, Adriana C. Rossi, Steven P. Salvatore, et al. "Treatment Outcomes in Monoclonal Immunoglobulin Deposition Disease (MIDD): A Two Center Experience." Blood 132, Supplement 1 (November 29, 2018): 5591. http://dx.doi.org/10.1182/blood-2018-99-112110.
Full textAbstract:
Abstract Background: Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of plasma cell dyscrasias in which deposition of immunoglobulin light and/or heavy chains results in organ dysfunction, most commonly affecting the kidneys. MIDD can present with new onset hypertension, hematuria, renal insufficiency and proteinuria. The rarity of MIDD contributes to the uncertainty regarding optimal therapy (typically targeting the clonal plasma cells), and the relationship between hematologic response and renal outcome. We report here the experience at Memorial Sloan Kettering Cancer Center and New York Presbyterian Hospital/Weill Cornell Medical Center. Methods: An electronic query of pathology records was performed to identify patients with a biopsy-proven diagnosis of MIDD. Patients were eligible for inclusion in this analysis if they had received treatment and had been subsequently followed at either institution. A retrospective review of clinical records extracted patients' baseline characteristics and treatment history. Hematologic responses were assessed according to International Myeloma Working Group uniform response criteria (Kumar, S. et al 2016 Lancet Oncol 17(8): e328-346) and renal organ responses were evaluated based on changes in serum creatinine (SCr), and proteinuria, a modification of criteria previously reported (Kourelis, T. V., et al 2016, Am J Hematol 91(11): 1123-1128.; Nasr, S.H. et al. 2009, J Am Soc Nephrol 20(9): 2055-2064. The primary objective was to determine the rate of hematologic response after initial therapy. Secondary objectives included: (i) Estimation of renal response rate; (ii) Identification of risk factors associated with renal response using the Wilcoxon Rank Sum and Fisher's Exact Tests. Results: Among 54 patients identified who were diagnosed and started treatment between 1/1999 and 1/2016, 29 met criteria for inclusion. Baseline characteristics at diagnosis included: Median age of 50 (range, 32-79); 17 (59%) were male; 22 (75%) had hypertension. Renal parameters at diagnosis: median SCr of 2.4 mg/dl (range, 0.4-19), median CrCl 23 ml/min (range, 4-131), median proteinuria 2383.7mg/24h (range 4.7-13,000), nephrotic-range proteinuria syndrome in 13 (45%), hematuria in 4/25 pts (16%; 4 unknown), 7 were on hemodialysis (HD) prior to initiation of therapy, and 26 (90%) patients had monoclonal kappa light chain deposits. Hematologic parameters included median free light chain ratio of 67.9 (2.8-1179.0), detectable M-spike in 11 pts with a mean level of 0.6 g/dL and median bone marrow plasmacytosis of 20% (range, 0-90%). Induction treatment regimens included bortezomib in 18 (62%), lenalidomide in 6 (21%), cyclophosphamide in 8 (28%), and 21 (73%) underwent autologous stem cell transplant (ASCT) during the course of their treatment. Outcomes are shown in Table 1. Hematologic response among the 29 pts at completion of first line therapy included an overall response rate (ORR) of 93% with sCR (N=14, 48%); CR (N=5, 17%), VGPR (N=6, 20%), PR (N=2, 6.9%), Not available (N=2, 7%). Renal response (Table 1) among 29 patients included CR (N=9, 31%), PR (N=14, 48%) and End Stage Renal Disease (ESRD) (N=6, 21%). Among 7 patients on HD at baseline, 3 remained on HD despite treatment, while 4 stopped HD after treatment, 2 as a result of the treatment and 2 after renal transplant. 3 patients progressed to ESRD and required HD during treatment. Baseline beta-2 microglobulin (B2M), SCr, and eGFR at diagnosis were factors associated with renal response (p<0.05). Hematologic response (CR vs. non-CR) was not associated with renal response (p=0.68) in this cohort. Conclusions: In this cohort, we observed a high rate of hematologic response (65.5% reaching CR) to upfront treatment regimens. A majority of patients received bortezomib-based regimens and ASCT. We observed a large proportion of patients whose renal impairment from MIDD improved significantly after receiving therapy directed at the underlying clonal neoplasm, with 75.8% reaching PR or better, nearly a third of patients achieving a renal CR, and 2/7 patients on HD at diagnosis discontinuing HD after treatment. Our experience presented here serves to inform the treatment approach of patients with MIDD. Given the scarcity of outcome data in MIDD, especially in the era of novel anti-myeloma therapy, prospective studies to optimize the management of these patients are needed. Disclosures Rossi: Celgene: Consultancy. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Korde:Amgen: Research Funding. Mailankody:Janssen: Research Funding; Juno: Research Funding; Physician Education Resource: Honoraria; Takeda: Research Funding. Lesokhin:Squibb: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Genentech: Research Funding; Janssen: Research Funding; Serametrix, inc.: Patents & Royalties: Royalties. Landgren:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hassoun:Oncopeptides AB: Research Funding.
49
Quintarelli, Concetta, Simona Sivori, Simona Caruso, Simona Carlomagno, Iolanda Boffa, Domenico Orlando, Marika Guercio, et al. "CD19 Redirected CAR NK Cells Are Equally Effective but Less Toxic Than CAR T Cells." Blood 132, Supplement 1 (November 29, 2018): 3491. http://dx.doi.org/10.1182/blood-2018-99-118005.
Full textAbstract:
Abstract Based on the clinical success observed in acute lymphoblastic leukemia (ALL) with chimeric antigen receptor engineered T (CAR T), we hypothesized that combining the specificity of a CAR with the innate allo-reactivity of KIR-mismatched NK cells might provide a powerful tool for adoptive cell therapy. The use of a third-party bank of CAR-NK cells offers the advantage of an immediate availability to be exploited in the allogenic setting and could be associated with a lower toxicity profile than CAR-T cells. In order to overcome regulatory and manufacturing hurdles associated with generation of CAR-NK cells, we developed a feeder-free culture resulting in a 3.2-log expansion after 20 days of culture. Specifically, natural cytotoxicity receptors (NCR) expressed on NK cells are stimulated in the presence of pleiotropic cytokines and expanded in GMP grade bioreactors. Expanded NK cells from healthy donors preserve a high percentage of CD56+ CD57- cells (85±13%), associated with high proliferative capability, and maintain the surface expression and the responsiveness of NCR and CD16. We proved that NK cells generated from 10 different healthy donors have high ability to recognize and eliminate different tumor types, including acute myeloid leukemia (AML) and ALL. After genetic modification with a retroviral vector encoding a CAR specific for CD19 antigen, transduction of activated NK cells averaged 38%±15% and the CAR.CD19 expression was stable over extended in vitro culture (60 days). Detailed phenotypic characterization of CAR-NK cells showed that CAR expression was not limited to the more mature NKG2A-/KIR+ cells, but rather was distributed across different NK subsets. We also demonstrated that NK and CAR-NK cells display significant anti-leukemia activity towards CD19+ leukemia and lymphoma cell lines (LCL 721.221, DAUDI and BV173) and primary blasts obtained from patients with B-cell precursor ALL (Bcp-ALL). Co-culture experiments using a 1:5 E/T ratio, showed that, while the anti-tumor activity was already remarkable with non-modified effector NK cells (60±30%, 71±33% and 54±23% of residual LCL 721.221, DAUDI and BV173 cells, respectively; p<0.05 vs T cells), it reached the highest level when CAR-NK cells were used as effectors (7±9%, 16±30% and 22±16% of residual LCL 721.221, DAUDI and BV173 cells, respectively; p<0.05 vs non-transduced NK cells). Importantly, INF-g production was significantly lower upon CAR-NK activation compared to CAR-T cells (DAUDI 384±194 ng/ml vs 1860±678 ng/ml, p=0.002). Functional analysis on primary Bcp-ALL blasts, demonstrate that CAR-NK cells exert high degree of leukemia control (on average 2.1±2% vs 5.4±1.6% with non-modified NK cells as effectors; p=0.04). An in vivo model of leukemia xenograft immunodeficient mice was used to evaluate whether CAR-NK cells are associated with a lower toxicity profile compared to CAR-T cells. While the in vivo antileukemia activity was superimposable between CAR-T and CAR-NK cells (mouse bioluminenscence at 20 days, 4.9x105 vs 6.6x105 photons/second, respectively; p=n.s. Figure A), mice treated with two i.v. infusions (day 0 and day 15) of 10x106 CAR.CD19 NK cells had a 100% overall survival (OS of 5 out of 5 mice) at 50 days compared to 20% of mice (1 out of 5) receiving 10x106 CAR.CD19 T cells (Figure B; p=0.01). Cytokine plasma level monitoring, performed on day +7 and +30 after effector cell infusion in the absence of leukemia persistence (as evidenced by a lack of bioluminescence signal), showed that mice engrafted with CD19+ leukemia and treated with CAR.CD19-NK cells have lower levels of circulating hIFN-g cytokine compared to mice treated with CAR.CD19-T cells at both day 7 (42±82 vs 330±346 ng/ml; p=0.05) and day 30 (0.9±0.7 vs 4148±667 ng/ml; p=0.05). These in vitro and in vivo data demonstrate the feasibility of clinical scale feeder-free expansion of non-modified NK cells and stably transduced CAR-NK cells. Both non-modified and gene-modified cells were capable of significant tumor killing, suggesting a multi-modal adoptive cell approach to treatment of leukemia. Since NK cells have been shown to be safely used in third-party setting (St. Jude Children's Research Hospital, USA; NCT00640796), we suggest that ex-vivo expanded, feeder-free NK cells can be universally applied for 'off-the-shelf' immuno-gene-therapy, and that their innate allo-reactivity can be safely harnessed to potentiate allogeneic cell therapy. Figure. Figure. Disclosures Locatelli: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees.
50
Зайнулгабидинов, Эрик Ренатович, Юрий Алексеевич Игнатьев, and Андрей Михайлович Петров. "ВЛИЯНИЕ ФИТОРЕМЕДИАЦИИ НА ПРОФИЛЬ УГЛЕВОДОРОДОВ НЕФТИ В АЛЛЮВИАЛЬНЫХ ДЕРНОВЫХ ПОЧВАХ." Российский журнал прикладной экологии, no. 2 (June 25, 2021): 53–60. http://dx.doi.org/10.24852/2411-7374.2021.2.53.60.
Full textAbstract:
Фиторекультивация почв, загрязненных нефтью и нефтепродуктами, рассматривается как один из перспективных подходов в биотехнологии. Эффективность этого метода зависит от под- бора культур. Объектом исследования являлась загрязненная нефтью аллювиальная дерновая легкосуглинистая почва. Рассматривались варианты с начальным содержанием нефти 5.4 г/кг, 9.7 г/кг и 21.8 г/кг. В качестве фиторемедиантов использовались однодольные и двудольные растения ‒ пшеница яровая (Triticum vulgare L.) и горох посевной (Pisum sativum L). Газохроматографическим методом изучено изменение углеводородного состава после фиторекультивационных мероприятий. На хроматограммах идентифицированы пики гомологов н-алканов диапазона С9‒С36 и углеводороды (УВ) неполярного и малополярного строения, образующие «изопреноидный горб». Стимулируя активность микроорганизмов в прикорневой зоне, рассматриваемые культурыоказывают различное влияние на деструкцию и преобразование остаточной нефти в зависимости от степени загрязнения. Существенное снижение концентрации УВ нефти к концу эксперимента (в 3.8 раза) отмечено в варианте с максимальным содержанием поллютанта в опыте с пшеницей. Отмечается обратная зависимость процентного содержания н-алканов от уровня остаточного содержания нефтепродуктов. Выделено 2 типа распределения неполярных УВ. Для вариантов с низким уровнем загрязнения характерна мономодальная форма. Второй тип имел бимодальное распределение и был типичен для опытных образцов с относительно высокой концентрацией. Профиль н-алканов характеризовался преобладанием четных гомологов в среднемолекулярной области. Полученные данные могут указывать, что наиболее вероятными продуцентами четных парафинов среднемолекулярного диапазона может быть биомасса микробиоты.
Библиографические ссылки
1. Габов Д.Н., Безносиков В.А., Кондратенок Б.М., Грузлев И.В. Насыщенные углеводороды в фоновых и загрязненных почвах Предуралья // Почвоведение. 2010. №10. С. 1190‒1196.
2. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М., Хабибуллин Р.Э. Особенности распределения нормальных алканов в современных дерново-подзолистых почвах // Вестник технологического университета. 2015. Т.18, №4. С. 271‒274.
3. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М., Хабибуллин Р.Э. Влияние длительности инкубации на состав нормальных углеводородов при разных уровнях начального содержания нефти в почве // Вестник технологическогоуниверситета. 2016. Т. 19, №10. С. 56‒60.
4. Зайнулгабидинов Э.Р., Игнатьев Ю.А., Петров А.М. Оптимизация метода потери массы при прокаливании для определения остаточного содержания органических соединений нефти в загрязненных почвах // Российский журнал прикладной экологии. 2021. №1. С. 64‒71.
5. Игнатьев Ю.А., Зайнулгабидинов Э.Р., Петров А.М. Изменение углеводородного состава нефтезагрязнённой дёрново-подзолистой почвы в стандартизированных условиях инкубации // Вестник технологического университета. 2014. Т. 17, №15. С. 256‒260.
6. Игнатьев Ю.А., Зайнулгабидинов Э.Р., Петров А.М. Применение метода прокаливания для определения содержания аллохтонных углеводородов нефти в почвах // Российский журнал прикладной экологии. 2018. №3. С. 34‒37.
7. Кальвин М. Химическая эволюция. М.: Мир, 1971. 283 с.
8. Каримуллин Л.К., Петров А.М., Вершинин А.А. Фиторекультивация и физиологическая активность нефтезагрязненной дерново-подзолистой почвы // Российский журнал прикладной экологии. 2016. №1. С. 14‒17.
9. Киреева Н.А., Водопьянов В.В. Мониторинг растений, используемых для фиторемедиации нефтезагрязненных почв // Экология и промышленность России. 2007. №9. С. 46‒47.
10. Киреева Н.А., Новоселова Е.И., Шамаева А.А., Григориади А.С. Биологическая активность чернозема выщелоченного, загрязненного продуктами сгорания попутного нефтяного газа, и возможности ее восстановления при фиторемедиации // Почвоведение. 2009. №4. С. 498‒503.
11. Киреева Н.А., Новоселова Е.И., Григориади А.С. Влияние загрязнения почв нефтью на физиологические показатели растений и ризосферную микробиоту // Агрохимия. 2009а. №7. С. 71‒80.
12. Киреева Н.А., Григориади А.С., Водопьянов В.В., Амирова А.Р. Подбор растений для фиторемедиации почв, загрязненных нефтяными углеводородами // Известия Самарского научного центра РАН. 2011. Т. 13, №5. С. 184‒187.
13. Киреева Н.А., Григориади А.С., Баширова Р.М., Ами-рова А.Р. Использование бархатцев прямостоячих Tagetes erecta L. для фиторемедиации почвы, загрязненной нефтяными углеводородами // Агрохимия. 2012. №5. С. 66–72.
14. Муратова А.Ю., Бондаренкова А.Д., Панченко Л.В., Турковская О.В. Использование комплексной фиторемедиации для очистки почвы, загрязненной нефтешламом // Биотехнология. 2010. №1. С. 77‒84.
15. Пахарькова Н.В., Прудкова С.В., Гекк А.С., Ларькова А.Н., Коростелева Н.С. Оптимизация выбора растений для биоремедиации почв, загрязненных нефтью и нефтепродуктами в условиях южной Сибири // Вестник КрасГАУ. Биологические науки. 2015. №8. С. 28‒32.
16. Петров А.А. Углеводороды нефти. М.: Наука, 1984. 264 с.
17. Утомбаева А.А., Петров А.М., Зайнулгабидинов Э.Р., Игнатьев Ю.А., Кузнецова Т.В. Динамика роста высших растений на рекультивированных нефтезагрязненных аллювиальных луговых почвах разного гранулометрического состава // Российский журнал прикладной экологии. 2020. №1. С. 60‒65.
18. Фатина П.Н., Лапаева И.В., Давыдова Е.А. Фиторемедиация – эффективный и экономический метод очистки почвы, загрязненной нефтью и нефтепродуктами // Защита окружающей среды в нефтегазовом комплексе. 2008. №5. С. 75‒78.
19. Eglinton G., Hamilton R.J. Leaf epicuticular waxes // Science. 1967. V. 56. P. 1322‒1335.
20. Ekpo B.O., Oyo-Ita O.E., Wehner H. Even-n-alkane/ alkene predominances in surface sediment from the Calabar River, SE Niger Delta, Nigeria // Naturwissenschaften. 2005. V. 92. Р. 341–346. DOI 10.1007/s00114-005-0639-8.
21. Marseille F., Disnar J.R., Guillet B., Noack Y. n-Alkanes and free fatty acids in humus and A1 horizon of soils under beech, spruce and grass in the Massif-Central (Mont-Loze Áre), France // European journal of soil science. 1999. V. 50. P. 433- 441. htpps://doi.org/10.1046/j.1365-2389.1999.00243.x
22. Jovančićević B., Vrvić M., Schwarzbauer J., Wehner H., Scheeder G., Vitorović D. Organic-geochemical differentiation of petroleum-type pollutants and study of their fate in Danube alluvial sediments and corresponding water (Pančevo Oil Refinery, Serbia) // Water, air soil pollution. 2007. V. 183. P. 225–238. DOI: 10.1007/s11270-007-9371-7
23. Jovančićević B. Identification, transformation and migration of petroleum-type pollutants in recent sediments and soil // Newsletter of European association of chemistry and the environment. 2002. №3. Р. 5–6.
24. Lei G.L., Zhang H.C., Chang F.Q., Pu Y., Zhu Y., Yang M.S., Zhang W.X. Biomarkers of modern plants and soils from Xinglong Mountain in the transitional area between the Tibetan and Loess Plateaus // Quaternary international. 2010. V. 218. P. 143–150. htpps://doi.org/10.1016/j.quaint.2009.12.009
25. Rao Z.G., Zhu Z.Y., Jia G.D., Zhang X., Wang S.P. Compound-specific hydrogen isotopes of long-chain n-alkanes extracted from topsoil under a grassland ecosystem in northern China // Science in China. Ser. D: Earth Sciences. 2011. V. 54, №12. P. 1902‒1911. htpps://doi.org/10.1007/s11430-011-4252-8
26. Wang Y., Fang X., Bai Y., Xi X., Zhang X., Wang Y. Distribution of lipids in modern soils from various regions with continuous climate (moisture-heat) change in China and their climate significance // Science in China. Ser. D.: Earth Sciences. 2007. V. 50, №4. Р. 600‒612. htpps://doi.org/10.1007/s11430-007-2062-9.