Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: 658.8 : 339.166.5.
Статті в журналах з теми "658.8 : 339.166.5"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "658.8 : 339.166.5".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Dale, David C., Steven P. Treon, David F. McDermott, Diego Cadavid, Xia Luo, Varun Garg, Weihua Tang, et al. "Oral Administration of Mavorixafor, a CXCR4 Antagonist, Increases Peripheral White Blood Cell Counts across Different Disease States." Blood 138, Supplement 1 (November 5, 2021): 2186. http://dx.doi.org/10.1182/blood-2021-152990.
Повний текст джерелаАнотація:
Abstract Introduction: Peripheral leukocyte deficiency is a common feature of multiple diseases and may render affected individuals susceptible to infections, both common and opportunistic. The CXCR4 chemokine receptor regulates the trafficking of leukocytes among the bone marrow, blood, and lymphatic system (Al Ustwani O, et al. Br J Haematol. 2014;164:15-23). Mavorixafor is an orally available investigational, small-molecule, selective antagonist of the CXCR4 receptor with potential to restore physiological trafficking and maturation of white blood cells (WBCs). Mavorixafor was previously shown to increase totals and subsets of WBCs in healthy volunteers and in a phase 2 clinical trial in adults with WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome (Stone N, et al. Antimicrob Agents Chemother. 2007;51(7):2351-2358; Dale D, et al. Blood. 2020;136(26):2994-3003). Here, we report the effect of daily oral administration of mavorixafor on peripheral WBC counts and subsets in patients with clear cell renal cell carcinoma (ccRCC), WHIM syndrome, and Waldenström's macroglobulinemia (WM). Methods: Percentage changes in total peripheral WBC count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and absolute monocyte count (AMC) from pretreatment levels were evaluated in the following settings: a phase 1/2 trial evaluating mavorixafor (200 mg twice daily or 400 mg once daily [QD]) in combination with axitinib (5 mg twice daily) in patients with advanced ccRCC who received ≥1 prior therapy; a phase 1b trial evaluating mavorixafor (400 mg QD) in combination with nivolumab (240 mg QD) in patients with metastatic ccRCC unresponsive to prior nivolumab monotherapy; a long-term extension of the aforementioned phase 2 trial evaluating mavorixafor 300 or 400 mg QD in patients with WHIM syndrome with pathogenic CXCR4 gain-of-function mutation and ANC ≤400/μL and/or ALC ≤650/μL; and an ongoing phase 1b trial evaluating mavorixafor (200 mg QD for 4 weeks, increased to 400 mg and 600 mg QD thereafter) in combination with ibrutinib (420 mg QD) in patients with WM with MYD88 and CXCR4 mutations. Results: In the study evaluating combination mavorixafor (400 mg QD) and axitinib in ccRCC, total WBC count, ANC, ALC, and AMC increased to 153%, 158%, 143%, and 182% of baseline after 4 weeks (n=49), and with increases sustained at 159%, 171%, 139% and 166% of baseline after 6 months' treatment (n=20). In the study evaluating mavorixafor in combination with nivolumab in ccRCC, total WBC count, ANC, ALC, and AMC increased to 146%, 143%, 141%, and 179% of baseline after 4 weeks (n=9), and with increases sustained at 147%, 136%, 152%, and 191% of baseline after 6 months (n=2). In an interim analysis of the phase 1b trial in WM, compared to screening values, total WBC count, ANC, ALC, and AMC increased to 192%, 170%, 219%, and 186% of baseline after 4 weeks (n=8), and with increases sustained at 163%, 192%, 106%, 172% of baseline after 6 months' (n=5) treatment. In the WHIM syndrome phase 2 extension, total WBC count, ANC, ALC, and AMC increased to 339%, 652%, 239%, and 486% of baseline after 6 months' (n=5) treatment, with annualized infection rate decreasing from 5.6 (SD ± 3.13) events at baseline to 2.2 (SD ± 0.93) events after 40 months. Mavorixafor was generally well tolerated, with manageable safety profile across all indications either alone or in combination with other drugs. Conclusions: Mavorixafor alone or in combination with other therapies is the first oral treatment to either acutely or chronically increase total peripheral WBCs 1.5- to 3-fold and WBC subsets across all disease populations examined, in both the presence (WHIM syndrome and WM) and absence (ccRCC and healthy volunteers) of CXCR4 gain-of-function mutation. Increases in WBC subsets occurred rapidly and were sustained during chronic treatment, with a larger treatment effect in patients with pre-existing cytopenia (WHIM syndrome) compared to patients without cytopenia at baseline (ccRCC and WM). Co-occurring reduction in infection burden was observed in the phase 2 trial in WHIM syndrome. Assessment of the beneficial effects of mavorixafor on total and WBC subsets is ongoing in a phase 3 trial of WHIM syndrome and a phase 1 trial of severe chronic neutropenia (SCN) that will assess the potential to correct cytopenias by elevating total WBC counts. Disclosures Dale: X4 Pharmaceuticals: Consultancy, Honoraria, Research Funding. Treon: AbbVie: Consultancy, Research Funding; Dana Farber Cancer Institute: Current Employment; Self: Patents & Royalties: Holder of multiple patents related to testing and treatment of MYD88 and CXCR4 mutated B-cell malignancies; BMS: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; X4: Research Funding. McDermott: Johnson and Johnson: Consultancy, Honoraria; Genentech: Research Funding; Eisia Inc.: Consultancy, Honoraria; Werewolf Therapeutics: Consultancy, Honoraria; Calithera Biosciences: Consultancy, Honoraria; X4 Pharmaceuticals: Research Funding; Iovance: Consultancy, Honoraria; EMD Serono: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Exelixis: Research Funding; Alkermes, Inc.: Consultancy, Honoraria, Research Funding; Eli Lilly and Company: Consultancy, Honoraria. Cadavid: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Luo: X4 Pharmaceuticals: Consultancy. Garg: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Tang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Jiang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Chen: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Taveras: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bhandari: X4 Pharmaceuticals: Current Employment.
2
Kang, Elizabeth M., Ellen M. Areman, Virginia David-Ocampo, Courtney Fitzhugh, Mary E. Link, Elizabeth J. Read, Susan F. Leitman, Griffin P. Rodgers, and John F. Tisdale. "Mobilization, collection, and processing of peripheral blood stem cells in individuals with sickle cell trait." Blood 99, no. 3 (February 1, 2002): 850–55. http://dx.doi.org/10.1182/blood.v99.3.850.
Повний текст джерелаАнотація:
Abstract Mobilized peripheral blood is increasingly used as the source of hematopoietic stem cells for allogeneic transplantation, currently the only curative approach for sickle cell anemia. However, the safety and feasibility of stem cell mobilization in individuals with sickle cell trait (SCT) has not been documented. This study is a prospective controlled trial to evaluate the safety and feasibility of peripheral blood stem cell (PBSC) mobilization in 8 SCT subjects and 8 control subjects matched for age and race. Mobilization with filgrastim 10 μg/kg subcutaneous daily for 5 days was followed by 12-L apheresis on the fifth day. Filgrastim administration was accompanied by similar symptoms in all subjects; no untoward adverse events occurred in either group, including sickle cell crises. CD34+ cell mobilization response was not significantly different between SCT and control subjects. Median CD34+ cell content was also similar in PBSCs collected from SCT versus control subjects, 6.8 versus 3.9 ×106 CD34+ cells/70 kg,P = .165. Red cell depletion from SCT products was not possible by using hydroxyethyl starch sedimentation but was achievable with ammonium chloride lysis. There was no evidence of gelling of SCT products after thaw, and no difference in cell recovery was seen among red cell–depleted versus nondepleted products. Cryopreservation in 5% dimethyl sulfoxide/6% pentastarch was associated with superior cell recovery (both SCT and control subjects) compared with 10% dimethyl sulfoxide (P = .001). The study concluded that filgrastim mobilization, large volume apheresis, processing, and cryopreservation appears to be safe in donors with SCT, allowing PBSC use for transplantation in patients with sickle cell anemia.
3
Lazo-Langner, Alejandro, Jeff Hawell, Michael J. Kovacs, Philip S. Wells, Dimitrios Scarvelis, Melissa Anne Forgie, and Marc Rodger. "A Systematic Review and Meta-Analysis of Proportions of Thrombosis and Bleeding in Patients Receiving Venous Thromboembolism (VTE) Prophylaxis After Orthopedic Surgery (OS). An Update." Blood 114, no. 22 (November 20, 2009): 3125. http://dx.doi.org/10.1182/blood.v114.22.3125.3125.
Повний текст джерелаАнотація:
Abstract Abstract 3125 Poster Board III-62 VTE is the most frequent complication of OS and it can be prevented through anticoagulant prophylaxis. Numerous studies have evaluated different agents for this purpose and there are new agents currently under development or recently approved for this indication. We conducted a systematic review of randomized controlled trials (RCT) evaluating administration of anticoagulants for VTE prophylaxis in OS and performed a MA of proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), symptomatic VTE and major bleeding episodes (as defined by the International Society on Thrombosis and Hemostasis). We included RCT comparing currently approved anticoagulants (head-to-head or placebo-controlled) for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, CT pulmonary angiography, or ventilation perfusion scan). Heterogeneity of proportions was evaluated using a chi2 test and pooled estimates of proportions were obtained using either a fixed or a random effects model in which the weights were estimated as proposed by Laird and Mosteller. We retrieved 74 studies including180 research arms and enrolling 71,012 patients. The total number of events and evaluable patients, percentage of events and 95% CI, and number of study arms included are shown in the table. We found differences in the percentage of VTE and bleeding events associated with the use of different anticoagulants for VTE prophylaxis after OS. Due to the nature of the analysis no effect measure can be estimated. These estimates might help to design future studies. Major VTE Total VTE Symptomatic VTE Major Bleeding Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) All patients LMWH 993/23692 5.96 (5.81, 6.11) 72 4068/22610 20.29 (20.04, 20.55) 80 193/19431 1.32 (1.27, 1.37) 35 476/28725 1.98 (1.93, 2.02) 70 UFH 234/2407 13.39 (12.86, 13.93) 14 596/2537 22.54 (22, 23.08) 17 11/339 3.24 (3.06, 3.43) 4 70/2849 2.75 (2.61, 2.89) 16 Warfarin 269/5677 6.28 (6.09, 6.46) 12 1317/4203 31.05 (30.44, 31.66) 12 71/4146 1.95 (1.83, 2.08) 6 96/6751 1.78 (1.69, 1.87) 12 Fonda 96/3673 3.81 (3.53, 4.09) 7 223/3477 6.82 (6.57, 7.07) 6 69/6398 1.06 (1.01, 1.1) 8 121/6576 1.63 (1.55, 1.71) 9 Riva 50/5025 2.02 (1.86, 2.19) 8 242/4595 13.05 (12.16, 13.94) 8 29/6252 0.46 (0.45, 0.48) 6 31/6643 0.63 (0.59, 0.68) 8 Dabi 149/4091 3.64 (3.59, 3.69) 6 834/4051 22.96 (21.91, 24.01) 6 26/3664 0.71 (0.67, 0.75) 4 67/5419 1.21 (1.17, 1.26) 6 Placebo 193/710 24.26 (23.17, 25.34) 10 379/816 49.35 (48.08, 50.62) 11 19/198 12.02 (10.32, 13.72) 3 12/753 1.59 (1.5, 1.68) 7 Total 1984/45275 129 7659/42289 140 418/40428 66 873/57716 128 Total Hip Arthroplasty LMWH 653/15978 6 (5.85, 6.16) 50 1817/14480 15.58 (15.35, 15.82) 55 81/11552 0.7 (0.69, 0.72) 19 306/18010 1.97 (1.92, 2.02) 45 UFH 187/1739 14.3 (13.64, 14.96) 11 354/1836 20.13 (19.46, 20.8) 13 11/246 4.47 (4.21, 4.73) 3 52/1451 3.2 (3.01, 3.39) 11 Warfarin 77/2758 4.28 (4.08, 4.48) 6 265/1273 20.82 (20.59, 21.04) 6 32/1833 1.75 (1.69, 1.81) 2 47/2856 2.23 (2.09, 2.37) 5 Fonda 28/1799 2.96 (2.58, 3.33) 3 85/1695 5.01 (4.91, 5.12) 2 15/2255 0.67 (0.63, 0.7) 2 69/2349 2.94 (2.87, 3.01) 3 Riva 25/2938 2.21 (1.95, 2.46) 5 73/2749 9.72 (8.92, 10.53) 5 10/3468 0.29 (0.27, 0.31) 3 14/3795 0.49 (0.44, 0.54) 5 Dabi 72/1803 3.99 (3.88, 4.11) 2 124/1766 7.02 (6.77, 7.27) 2 21/2293 0.92 (0.91, 0.93) 2 38/2309 1.65 (1.58, 1.72) 2 Placebo 105/414 26.01 (24.76, 27.27) 7 174/418 45.43 (43.74, 47.13) 7 4/147 2.72 (2.46, 2.98) 2 3/388 0.77 (0.69, 0.86) 5 Total 1147/27429 84 2892/24217 90 174/21794 33 529/31158 76 Total Knee Arthroplasty LMWH 277/6916 4.45 (4.34, 4.55) 25 2062/7326 30.72 (30.37, 31.07) 32 83/4902 1.69 (1.66, 1.73) 11 89/7808 1.14 (1.12, 1.16) 26 UFH 42/638 6.58 (6.39, 6.78) 3 226/638 35.42 (35.05, 35.79) 3 0/93 NE 1 3/318 0.94 (0.84, 1.05) 2 Warfarin 192/2919 8.1 (7.88, 8.32) 9 1052/2930 39.36 (38.69, 40.02) 9 39/2056 1.9 (1.84, 1.96) 3 28/3407 0.82 (0.79, 0.85) 8 Fonda 23/452 9.3 (7.93, 10.67) 2 45/361 12.47 (12.12, 12.81) 1 3/517 0.58 (0.51, 0.65) 1 12/601 2 (1.88, 2.11) 2 Riva 25/2087 1.2 (1.15, 1.24) 3 169/1846 18.55 (16.47, 20.63) 3 19/2784 0.68 (0.65, 0.71) 3 17/2848 0.6 (0.57, 0.63) 3 Dabi 77/2288 3.37 (3.32, 3.41) 4 710/2285 30.98 (30.42, 31.55) 4 5/1371 0.36 (0.32, 0.41) 2 29/3110 0.93 (0.89, 0.98) 4 Placebo 88/296 27.12 (24.54, 29.7) 4 205/398 55.19 (53.53, 56.84) 5 15/51 29.41 (28.16, 30.66) 1 9/365 2.47 (2.31, 2.62) 4 Total 724/15596 50 4469/15784 57 164/11774 22 187/18457 49 LMWH Low molecular weight heparin, UFH unfractionated heparin, Riva Rivaroxaban, Dabi Dabigatran etexilate Disclosures Lazo-Langner: Boehringer Ingelheim: Honoraria. Rodger:Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding.
4
Bonig, Halvard, Annette Wundes, Kai-Hsin Chang, Sylvia Lucas, and Thalia Papayannopoulou. "Hematopoietic Stem/Progenitor Cells (HSPC) Mobilization Parameters in Patients Chronically Treated with the CD49d Blocking Antibody Natalizumab." Blood 110, no. 11 (November 16, 2007): 177. http://dx.doi.org/10.1182/blood.v110.11.177.177.
Повний текст джерелаАнотація:
Abstract Blockade of CD49d-mediated lymphocyte trafficking has been used therapeutically for certain autoimmune diseases. In addition to effects on mature lymphocytes, in mice and monkeys CD49d blockade also mobilizes immature hematopoietic cells from bone marrow (BM), capable of complete long-term engraftment despite a partial BM seeding defect. The aim of these studies was to ascertain effects on the biology of HSPC mobilization of single or chronic CD49d blockade in Multiple Sclerosis (MS) patients receiving disease-modifying treatment with the anti-functional anti-CD49d antibody, Natalizumab. These studies represent the first observations on HSPC mobilization by anti-CD49d antibodies in humans and on chronic exposure to a mobilizing agent. Circulating CD34+ cells (1.8±0.4/μL) and CFU-C (638±128/mL) were normal in MS patients (n=9) prior to the first Natalizumab infusion (normal controls: 1.3±0.1/μL CD34+ cells, 608±129/mL CFU-C). In chronically treated patients (i.e patients who had received ≥5 prior doses of Natalizumab) HSPC numbers were significantly elevated 30 days after the last infusion (CD34+ cells 9.0±1.2/μL, CFU-C 3243±332/mL, n=10, p<0.005). The blood of chronically Natalizumab-treated subjects also contained SCID-repopulating cells (n=3). After the first Natalizumab infusion, peripheral blood CD34+ cells and CFU-C were significantly increased over pre-treatment values (CD34+ cells 1.6±0.2/μL vs. 8.0±2.1/μL, CFU-C 414±161/mL vs. 2560±726/mL, n=7, p<0.005), indicating that a single dose of Natalizumab was sufficient to elicit similar mobilization levels as in chronic recipients. Renewed Natalizumab infusion in “chronic” Natalizumab-recipients did not result in additional mobilization, compared to values from just before that infusion (CD34+ cells 7.9±1.7/μL vs. 7.9±0.9/μL, CFU-C 3133±335/mL vs. 3525±305/mL, n=4). These data indicate that in the absence of CD49d-mediated BM retention a new equilibrium is established between HSPC in BM and in circulation. In long-term Natalizumab recipients a total of ca. 50x10E6 CD34+ cells (8 CD34+ cells/μL * 6L of blood) are in circulation at any given time. Considering the documented short half-life of circulating HSPC, (100 min in the mouse) this implies that approximately 700x10E6 CD34+ cells/day are trafficking in the average Natalizumab recipient. Whether the elevated numbers of circulating HSPC play a clinically relevant role for Natalizumab-treated MS patients is currently unclear. Given reports of MS flares under G-CSF, we propose that “steady-state” apheresis without additional mobilizing agents may be a safe and effective alternative to G-CSF if MS patients on Natalizumab are considered for autologous HSPC transplantation, an emerging treatment for refractory MS. The usefulness of Natalizumab as a mobilizing agent is likely restricted to the autologous setting, given the risk of immunization against Natalizumab and its prolonged effects. Instead, short-acting small-molecule inhibitors of CD49d could be developed as a mobilizing strategy for patient groups intolerant or unresponsive to G-CSF, alone or in combination with other novel mobilizing agents.
5
de Lima, Luiz Rodrigo Augustemak, Diego Augusto Santos Silva, Kelly Samara da Silva, Andreia Pelegrini, Isabela de Carlos Back, and Edio Luiz Petroski. "Aerobic Fitness and Moderate to Vigorous Physical Activity in Children and Adolescents Living with HIV." Pediatric Exercise Science 29, no. 3 (August 2017): 377–87. http://dx.doi.org/10.1123/pes.2017-0036.
Повний текст джерелаАнотація:
Purpose:To examine aerobic fitness, total moderate to vigorous physical activity (MVPA) and also patterns in terms of MVPA between children and adolescents with human immunodeficiency virus (HIV) and controls, and to determine whether differences, if any, are associated with HIV, sex and highly active antiretroviral therapy (HAART).Method:A cross-sectional analysis was carried out with 130 children and adolescents, aged between 8 and 15 years, divided into two groups (HIV group= 65 patients, control group= 65 healthy participants). Total MVPA was measured by accelerometers and 5 and 10-min bouts were estimated. The peak oxygen uptake (peak VO2) was measured by breath-by-breath respiratory exchange in an incremental cycle ergometer test.Results:HIV-positive participants had lower peak VO2 (39.2 ± 6.8 vs. 44.5 ± 9.1 ml.kg-1min-1), lower bouts of MVPA of 5-min (19.7 ± 16.6 vs. 26.6 ± 23.5) and 10-min (3.6 ± 3.9 vs. 5.8 ± 7.2), but similar total MVPA (49.5 ± 28.9 vs. 49.1 ± 30.6 min.day-1). HIV infection in untreated, nonprotease inhibitors (PI)- based HAART and PI-based HAART patients was associated with lower 8.5 (95%CI= 12.5–4.6), 7.1 (95%CI= 10.6–3.6) and 4.5 (95%CI= 7.0–2.0) ml.kg-1min-1 of peak VO2.Conclusion:Children and adolescents with HIV demonstrated lower aerobic fitness compared with the controls and the absence of HAART may increase peak VO2 impairment. Lower bouts of MVPA were also observed in HIV group despite the similar values of total MVPA of controls.
6
Micallef, Ivana, Stephen M. Ansell, Francis Buadi, David Dingli, Angela Dispenzieri, Dennis Gastineau, Morie Gertz, et al. "A Risk Adapted Approach Utilizing Plerixafor in Autologous Peripheral Blood Stem Cell Mobilization." Blood 114, no. 22 (November 20, 2009): 3211. http://dx.doi.org/10.1182/blood.v114.22.3211.3211.
Повний текст джерелаАнотація:
Abstract Abstract 3211 Poster Board III-148 Although autologous stem cell transplantation (ASCT) has become standard of care for many patients with hematologic malignancies, many patients fail to collect a minimum number of CD34 + stem cells to support high dose chemotherapy and ASCT. Recently, plerixafor, a CXCR4 antagonist, was FDA approved for use in combination with G-CSF for autologous peripheral blood stem cell mobilization in patients with NHL or Multiple Myeloma. In February 2009, we commenced a risk adapted approach to the utilization of plerixafor. The study was restricted to patients mobilized with GCSF alone and patients undergoing chemotherapy primed PBSC mobilization were excluded. Peripheral blood stem cell mobilization was commenced with G-CSF at 10 mcg/kg/day. On day 4, a peripheral blood (PB) CD34 count was measured. For patients whose PB CD34 was ≥10/μL, apheresis was commenced the following morning. For patients whose PB CD34 was <10/μL, it was measured again on day 5; if ≥10/μL then apheresis was commenced the following morning. If PB CD34 was <10/μL on day 5, plerixafor (0.24 mg/kg sc) was administered on the evening of day 5 and apheresis was commenced the following day (Group A). In addition, during apheresis, for patients whose collection yield was < 0.5 × 106 CD34/kg, in the absence of instrument failure or problems with the collection procedure, plerixafor was added (Group B). Morning administration of G-CSF and evening dosing of plerixafor continued daily until apheresis was complete. From February to July 2009, 174 mobilization attempts occurred; 27 with chemotherapy and 147 with cytokines alone. The 147 pts who underwent mobilization with cytokines alone are presented here. The underlying diagnosis was as follows: Myeloma 61 pts, NHL 54 pts, Amyloid 17 pts, Hodgkin 10 pts, POEMS 4 pts and 1 pt with a solid tumor. For the entire group the median number of CD34 cells collected was 5.5 × 106 CD34/kg (range 0.1-17). The median number of apheresis was 3 (range 1-12). 67 patients (46%) received plerixafor; 37 patients started plerixafor during mobilization (Group A) and 30 patients during collections due to a poor yield (Group B). 12 pts of the 37 received plerixafor on day 4 because of prior mobilization failure or high risk of mobilization failure and are included in Group A. Table 1 outlines the details of mobilization and collection by groups. By disease category, of the 61 patients with MM, 28 (46%) received plerixafor (8 Group A and 20 Group B). Median apheresis in all the MM pts was 2 (range 1-12) with a total of 6.8 × 106 CD34/kg (2.2-16.7). In the 54 NHL pts, 32 (59%) received plerixafor (24 Group A and 8 Group B). Median apheresis for all pts with NHL was 3 (range 1-7) with a total of 4.6 × 106 CD34/kg (range 0-11.4). Overall, only 7 of 147 (5%) mobilization attempts failed to achieve a minimum of 2 × 106 CD34/kg. This compares to a 22% failure rate prior to institution of this risk adapted approach. In conclusion, implementing this risk adapted approach allows poor mobilizers to be identified promptly and for plerixafor to be initiated during mobilization and collection, thereby reducing the number of mobilization failures. In patients who predictably would not have successful collection based on a PB CD34 <10/μL, addition of plerixafor results in a majority of patients achieving an adequate collection. This risk adapted approach may be more cost effective than reattempting mobilization after a prior failure or utilizing combination G-CSF and plerixafor for upfront mobilization. Table 1. Mobilization and Collection data. All patients N=147 Group A1 N=37 Group B2 N=30 No Plerixafor N=80 PB CD34 day 4 Median 11 0 7 19 Range 0-331 0-7 0-32 0-331 PB CD34 day 5 Median 10 4.5 12 15 Range 0-51 2-9 11-23 9-51 Apheresis Yield Median 5.5 4.4 6.0 6.2 Range 0.1-17 3.1-12.7 3.0-12.2 2-17 Number of Apheresis Median 3 3 5 2 Range 1-12 1-7 4-12 1-8 Days of Plerixafor Median n/a 3 2 n/a Rang 1-7 1-8 1 Group A – Plerixafor initiated prior to apheresis 2 Group B – Plerixafor initiated during apheresis Disclosures No relevant conflicts of interest to declare.
7
Barreira, S. C., A. R. Cruz-Machado, A. L. Fernandes, I. Genrinho, G. Sequeira, P. Monteiro, and J. E. Fonseca. "AB1145 PRESCRIPTION PATTERNS AND DISEASE ACTIVITY IN PORTUGUESE WOMEN OF CHILDBEARING AGE WITH RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS AND JUVENILE IDIOPATHIC ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1862.1–1863. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1976.
Повний текст джерелаАнотація:
Background:Disease activity (DA) at conception is one of the main predictors of pregnancy outcomes in women of childbearing age (WoCBA) with rheumatic diseases. Teratogenicity and unawareness about pregnancy compatibility of some disease-modifying anti-rheumatic drugs might limit the choice of treatment in WoCBA.Objectives:To assess differences in prescription patterns between WoCBA with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) and comparator groups, namely postmenopausal women (PMW) and age-matched men. Evaluate DA in WoCBA comparing to the aforementioned groups.Methods:Observational transversal study, using data from the portuguese registry of rheumatic diseases (Reuma.pt) from 3 portuguese centers. Adult patients (pts) with the diagnosis of RA, PsA, AS or JIA were allocated to the following groups: WoCBA (aged 18–44y), young men (YM) (18–44y), PMW (≥ 45y) and matched men (≥45y). Demographic and clinical variables are described as means or frequencies. Differences between groups regarding therapy and DA were assessed with Chi-square and ANOVA tests. Linear and logistic regression models were used to find predictors of DA and prescription patterns.Results:2133 pts were included, 69.9% female with a mean age of 55.96±15.85 y. 1437 pts were diagnosed with RA, 305 with PsA, 254 with AS and 137 with JIA. Patterns of prescription are detailed in table 1. WoCBA were less likely to be treated with glucocorticoids than PMW (OR 0.66 95%CI 0.44-0.99). WoCBA were 1.76 times more likely to be treated with MTX than YM (95%CI 1.04-2.97). Certolizumab was specially prescribed in WoCBA (OR 13.8, 95%CI 1.4-132.8). WoCBA had significantly higher DA scores than YM (DAS28 3.03±1.39 vs 2.32±1.18 and BASDAI 3.55±2.0 vs 2.43±1.66).Table 1.Prescription patternsMedications, n (%)A -WoCBA(N=256)B - Young Men(N=161)C - Post menopausal Women(N=927)D - MenN=340Chi-square testNSAIDs143 (55.9)111(68.9)472 (50.9)169 (49.7)p<0.001Glucocorticoids106 (41.4)31 (19.3)625 (67.4)154 (45.3)p<0.001csDMARDs- Methotrexate149 (58.2)60 (37.3)663 (71.5)197 (57.9)p<0.001- Leflunomide12 (4.7)4 (2.5)45 (4.9)2 (0.6)p=0.003- Sulfassalazine9 (3.5)5 (3.1)39 (4.2)9 (2.7)NS- Hydroxychloroquine36 (14.1)4 (2.5)117 (12.6)18 (5.3)p<0.001bDMARDs- Etanercept48 (18.8)29 (18.0)140 (15.1)66 (19.4)NS- Infliximab9 (3.5)11 (6.8)36 (3.9)30 (8.8)p=0.002- Adalimumab17 (6.6)15 (9.3)47 (5.1)27 (7.9)NS- Golimumab15 (5.9)18 (11.2)37 (4.0)30 (8.8)p<0.001- Certolizumab10 (3.9)0 (0)2 (0.3)2 (0.6)p<0.001- Tocilizumab12 (4.7)2 (1.2)71 (7.7)10 (2.9)p<0.001- Rituximab5 (1.9)0 (0)50 (5.4)4 (1.2)p<0.001- Abatacept0 (0)0 (0)9 (1)0 (0)NS- Secukinumab1 (0.4)4 (3.5)8 (0.9)2 (0.6)NS- Ustekinumab1 (0.4)3 (1.9)5 (0.5)0 (0)NStsDMARDs4 (1.6)1 (0.6)9 (0.9)0 (0)NSbDMARDs – biologic disease modifying antirheumatic drugs, csDMARDs – conventional synthetic disease modifying antirheumatic drugs, NSAIDs – non-steroidal anti-inflammatory drugs, tsDMARD – targeted synthetic disease modifying antirheumatic drugs, WoCBA – women of childbearing ageConclusion:Certolizumab was prescribed preferentially in WoCBA, who alsoreceived more MTX than YM. Nevertheless, DA in this group was not well controlled, which may influence future pregnancy outcomes. Ensuring tight DA control in WoCBA through proper and ideally no teratogenic medication remains an unmet clinical need.Disclosure of Interests:None declared
8
Andiru, G. A., C. C. Pasian, and J. M. Frantz. "Quantifying Water and Nutrient Losses with Hose Irrigation." Journal of Environmental Horticulture 33, no. 1 (March 1, 2015): 29–32. http://dx.doi.org/10.24266/0738-2898-33.1.29.
Повний текст джерелаАнотація:
The amount of water, nitrogen (N), phosphorous (P), and iron (Fe) lost from potted impatiens (Impatiens wallerana Hook. f.) plants fertilized with either controlled-release fertilizer (CRF) of varying longevities or a water-soluble fertilizer (WSF), with irrigation provided with a hose in all treatments, was quantified. The plants were grown in a sphagnum peat-based soilless substrate containing either CRF [Osmocote Plus 16-9-12 (16-3.9-10-0.46 N:P:K:Fe), 5 to 6 month and or 8-to 9 month longevities] incorporated (6.8 kg·m−3 or 11.5 lb·yd−3) throughout the substrate and compared with plants fertigated with a WSF [Peters Professional 20-10-20 (20-4.4-1.66-0.1 N:P:K:Fe) at 150 mg·L−1 (150 ppm) N]. The container-grown plants were placed on top of plastic cups and located inside a plastic box. Municipal water or mineral nutrient solution leached from each container and lost between containers was captured, quantified and analyzed for N, P, and Fe concentrations. As an average for the three treatments, 25.6% of the total water applied was leached out of the pots and 34% fell between the pots. Six weeks after starting the experiment, leachate from pots fertilized with WSF had approximately a 92% higher concentration of N, 96% more P, and 69% more Fe than the concentrations in leachate from CRF-fertilized pots. These results quantify the assumed inefficiencies of using a hose as the primary fertilizer delivery method.
9
Kotchetkov, Rouslan, Esther Masih-Khan, Chia-Min Chu, Young Trieu, Saima Dean, Manjula Maganti, Christine I. Chen, Vishal Kukreti, Suzanne Trudel, and Donna E. Reece. "Secondary Myelodysplastic Syndrome/Acute Myeloblastic Leukemia During Lenalidomide-Based Regimens in Relapsed and/or Refractory Multiple Myeloma Patients: Single Center Experience." Blood 120, no. 21 (November 16, 2012): 1867. http://dx.doi.org/10.1182/blood.v120.21.1867.1867.
Повний текст джерелаАнотація:
Abstract Abstract 1867 Secondary myelodysplastic syndrome and acute myelogenous leukemia (2° MDS/AML) are well-known complications that can occur after alkylating agent therapy for multiple myeloma (MM) or other cancers. However, until recently, the survival of MM pts was relatively short, a feature which may have contributed to a relatively low reported incidence of this complication in MM. The introduction of novel agents has improved survival rates of MM pts; lenalidomide (len) + dexamethasone–currently approved for MM after one prior therapy– is one of the main regimens that has contributed to this finding. Since alkylating agents, either given orally or as part of high-dose melphalan + ASCT, still remain an important component of MM therapy, more pts may survive to be at risk for 2° MDS/AML. Using the MM database at PMH, we retrospectively reviewed the charts of patients with relapsed/refractory (rel/ref) MM treated with len-based regimens (>1 cycle) to determine the incidence and characteristics of 2° MDS/AML that developed during this therapy. Between 06/2006 and 08/2012 we identified 230 patients having received len-based therapy: len + corticosteroids 222 patients, len alone 8 patients, cyclophosphamide + len + prednisone (CPR) 32 patients. 2° MDS/AML developed in 9 patients (3.9%) at a median of 89.6 months (range 30–188) from the time of diagnosis of MM and 22.4 (2–56.6) months from the time of initiation of len regimens. The median follow-up from start of len was 1.6 years, and from the start of diagnosis 7.5 years. The median duration of len treatment was 9.4 months. The MDS/AML cytogenetic changes were variable, but four patients had deletions of all or part of chromosome 5. None of the 2° MDS/AML had translocation t(4;14), as compared to 5.9% in (−) MDS/AML subgroup. The characteristics of patients at the time of starting len, in those who later developed (+) or did not develop (−) 2° MDS/AML during therapy, are shown in Table 1. Cumulative incidence of 2° AML/MDS from time of diagnosis to time of 2° AML/MDS is 4.5% [95% CI 2.2–9.2%] at 15 years. Cumulative incidence of 2° AML/MDS from starting time of len to time of AML/MDS is 5% [95% CI 2.4–10.4%] at 5 years. The incidence of 2° MDS/AML among those who had prior oral alkylators (OA) and/or concomitant OA was 10.5% (2/19 patients), concomitant cyclophosphamide only 7.6% (1/13), prior OA only 1.9% (3/152), and 6.5% for those who did not receive prior/concomitant OA (3/46). Grade 3–4 neutropenia occurred during len in 44% versus 58% in those with and without 2° MDS/AML, respectively. G-CSF was used in 56% of pts who developed MDS compared with 53% who did not. We conclude: 1) The cumulative incidence of MDS/AML from starting len to time of 2° AML/MDS was 5% at 5 years; 2) patients who developed 2° MDS/AML while on len regimens were slightly older, had slight male predominance, higher beta-2-microglobulin, creatinine and platelet count, less often received prior ASCT, thalidomide, and bortezomib, but had longer exposure to len; 3) the relationship with OA is not entirely certain, but it appears that those with prior and concomitant exposure to OA have the highest incidence of this complication, which is most often seen in prolonged len treatment. Table 1. Patient characteristics (n=230) Feature ALL patients (+) MDS/AML (–) MDS/AML Number of patients 230 9 221 Median age, years 61 (31–80) 68 (53–76) 61 (3–80) Male 134 (58%) 6 (67%) 128 (56%) Median baseline ANC, × 109/L 2.8 (0.9–61.4) 3.0 (1.5–5.1) 2.8 (0.9–61.4) Median baseline β-2 microglobulin (nmol/L) 222 (43–1695) 300 (133–481) 222 (43–1695) Median baseline pl count, × 109/L 156 (5–479) 200 (43–277) 156 (5–479) Median baseline creatinine, μmol/L 87 (39–515) 97 (56–117) 86 (39–515) Median # prior regimens 2 (0–6) 2 (1–5) 2 (0–6) Prior alkylating agents (all) 218 (95%) 9 (100%) 209 (95%) Prior oral alkylators 167 (73%) 6 (67%) 162 (73%) Prior ASCT 187 (81%) 2 (78%) 180 (81%) Prior thalidomide 132 (57%) 3 (33%) 129 (58%) Prior bortezomib 109 (47%) 3 (33%) 106 (48%) Concomitant cyclophosphamide 32 (13.9%) 3 (33%) 29 (13%) G-CSF use 123 (53%) 5 (56%) 118 (53.39%) Median duration of Len (mo, range) 9.4 (0.1–67.2) 22.8 (6.6–56.6) 6.8 (0.1–67.2) Disclosures: Chen: Johnson & Johnson, Lundbeck, Celgene: Consultancy; Roche: Honoraria; Johnson & Johnson, Celgene, GlaxoSmithKline: Research Funding. Kukreti:Roche: Consultancy, Honoraria; Celgene: Honoraria; Janssen: Honoraria. Reece:Janssen: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium Pharmaceuticals: Research Funding.
10
Strati, Paolo, Kari Chaffee, Sara Achenbach, Susan M. Schwager, Timothy G. Call, Neil E. Kay, James Cerhan, Susan L. Slager, and Tait D. Shanafelt. "Disease Progression and Complications Are the Main Cause of Death in Patients with Chronic Lymphocytic Leukemia (CLL) Independent of Age and Comorbidities at Diagnosis." Blood 126, no. 23 (December 3, 2015): 5265. http://dx.doi.org/10.1182/blood.v126.23.5265.5265.
Повний текст джерелаАнотація:
Abstract Introduction. CLL primarily affects elderly individuals who frequently have comorbid health conditions. It is typically assumed non-CLL-related etiologies will be the ultimate cause of death for most CLL patients, particularly those with comorbid conditions at diagnosis. Methods. Between 9/2002 and 11/2014, 1174 patients with newly diagnosed CLL were enrolled in a prospective cohort study evaluating the natural history of CLL. Comorbidities were prospectively recorded at the time of diagnosis. Comorbidities arising during the course of disease were not considered for this analysis. Standardized longitudinal follow-up was performed in all patients every 6 months for the first 3 years after diagnosis and annually thereafter through 04/2015. Internal and external medical records, death certificates, and information from next of kin were centrally reviewed to determine cause of death, using a standardized protocol. Categorical and continuous variables were evaluated using the c2 or Fisher exact tests and the Mann-Whitney test, as appropriate. Results. Baseline characteristics at time of CLL diagnosis are shown in the Table. Over 80% of patients had 2 or more comorbidities at diagnosis (median 3, range 0-11). After a median follow up of 5 years, 224 (19%) patients have died. The cause of death could be accurately determined in 183 (82%) of these patients. The cause of death was due to CLL in 135 (74%), including 84 (46%) CLL progressions, 14 (8%) infections, and 37 (20%) other cancers. Death was due to non-CLL-related causes (such as congestive heart failure, stroke or chronic obstructive pulmonary disease) in the remaining 48 (26%) patients. On univariable analysis, age and number of comorbid health conditions were not related to whether or not the cause of death was related/unrelated to CLL. The only specific co-morbid condition at diagnosis that predicted for non-CLL related death was stroke (8% vs 1%, p=0.04). Unmutated IGHV was the only prognostic factor thatpredicted greater likelihood of CLL-related death (70% vs 50%, p=0.03). Conclusions. The majority of patients with CLL have multiple comorbidities at time of diagnosis. Despite this fact, CLL progression and/or CLL-related complications are the primary cause of death. The number and type of comorbidities at diagnosis have minimal relationship to whether or not the ultimate cause of death was CLL-related. In contrast, the CLL-specific characteristic IGHV status (but interestingly not FISH defects) correlates with cause of death. Collectively, these findings illustrate the need for more effective CLL therapy, particularly treatments that can be tolerated by patients with comorbid health conditions. It is hoped the signaling inhibitors may help address this unmet need. Table. Number (%), median [range] N=1174 Age (years) 63 [23-89] Males Females 791 (67) 383 (33) Creatinine-Clearance > (mL/min) 86 [10-252] B2M (mg/dL) 2.3 [1.1-13.2] Rai stage 0 I-II III-IV 604 (52) 512 (38) 54 (10) CD49d positive negative 277 (30) 638 (70) CD38 positive negative 332 (30) 780 (70) ZAP70 positive negative 380 (37) 650 (63) IGHV unmutated mutated 394 (44) 506 (56) FISH del13q negative +12 del11q del17p 395 (40) 175 (18) 276 (28) 90 (9) 50 (5) Comorbid health conditions Other cancers 237 (20) Stroke 38 (3) Cardiac disease 326 (28) Hypertension 472 (40) Respiratory 210 (18) Endocrinologic 165 (14) Diabetes 118 (10) Hyperlipidemia 485 (41) Rheumatologic 489 (42) Gastrointestinal 384 (33) Genitourinary 412 (35) Psychiatric 197 (17) DVT/PE 33 (3) Substance abuse 58 (5) Sexually transmitted disease 35 (3) Obesity 376 (32) # of Comorbidities 0 1 2 3 4 > 4 66 (6) 148 (13) 203 (17) 220 (19) 206 (17) 331 (28) Disclosures Kay: Hospira: Research Funding; Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Tolero Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding.
11
Duran, Ignacio, Pablo Maroto, Cristina Suárez, Daniel E. Castellano, Xavier Garcia del Muro, Luis Costa, Lidia Martin-Couce, et al. "Analysis of overall survival (OS) based on early tumor shrinkage in the phase III METEOR study of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC)." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 550. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.550.
Повний текст джерелаАнотація:
550 Background: In the phase 3 METEOR study (NCT01865747), cabo improved OS (median 21.4 vs 16.5 mo; HR, 0.66; 95% CI, 0.53–0.83), progression-free survival and objective response rate compared with eve in patients (pts) with previously treated advanced RCC (Choueiri 2016). Retrospective studies have shown that early tumour shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC (Grunwald 2015; Grunwald 2016); here we evaluate its impact on OS in METEOR. Methods: In total, 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd), stratified by MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 wk for the first 12 mo and every 12 wk thereafter. Median OS was estimated for pts with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8); data cutoff, 2 October 2016 (Motzer 2018). Results: Median follow-up was 28 mo (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) mo with cabo and 2.14 (1.9, 9.2) mo with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%) and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%; Table). Median OS with cabo vs eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs 10.2 mo (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p<0.05). Median OS with cabo vs eve for pts with any eTS was 23.7 (95% CI, 21.7–27.7) vs 17.3 mo (95% CI, 15.4–20.8), respectively; (stratified HR, 0.62; 95% CI, 0.48–0.80; p<0.05). OS was similar for cabo and eve for pts with no eTS. Conclusions: Cabo demonstrated a higher rate and greater magnitude of eTS at first post-baseline scan compared with eve, and eTS was associated with prolonged OS in pts treated with cabo. Clinical trial information: NCT01865747. [Table: see text]
12
Saleh, Ramadan, Essam Nada, Ahmed F. Hamed, and Wesam M. Hussien. "Epidemiologic Trends of Viral Skin Infections in Egypt: A Cross-Sectional Hospital-Based Study." Dermatology Research and Practice 2019 (March 27, 2019): 1–4. http://dx.doi.org/10.1155/2019/5469726.
Повний текст джерелаАнотація:
Viral skin infections (VSIs) were ranked among the top 50 prevalent diseases in 2010. The objective of this study was to determine the epidemiologic features of VSIs in patients attending a dermatology clinic in Egypt from June 2010 to May 2011. Patient’s residence, occupation, housing data, and family history of similar conditions were recorded. Categorical data were recorded as frequencies and percentages and were compared by Chi square test. P value < 0.05 was significant. Diagnosis of VSIs was made in 1000/20322 (4.9%) patients. Out of the 1000 patients with VSIs, 580 (58.0%) were residents of rural areas and 420 (42.0%) were residents of urban areas (p = 0.02). Out of the 1000 patients, 489 (48.9%) were females and 511 (51.1%) were males (p = 0.25). The breakdown of 1000 patients with VSIs indicated diagnosis of viral warts in 673 (67.3%), chickenpox (CP) in 200 (20.0%), herpes simplex (HS) facialis in 50 (5.0%), herpes zoster (HZ) in 42 (4.2%), molluscum contagiosum (MC) in 27 (2.7%.0), and anogenital warts in 8 (0.8%) cases. Overcrowding (sharing a bedroom by more than 3 persons) was recorded in 652/1000 (65.2%) of the patients with VSIs [165/200 (82.5.3%) in CP, 36/50 (72%) in HS facials, 427/673 (63.4%) in viral warts, 14/27 (51.9%) in MC, and 10/42 (23.8%) in HZ]. Family history of a similar condition was positive in 329/1000 (32.9%) of the patients with VSIs [142/200 (71.0%) in CP, 177/673 (26.3%) in viral warts, 5/27 (18.5%) in MC, and 4/50 (8%) in HS facialis]. In conclusion, viral warts and CP were the commonest VSIs diagnosed in patients who attended a dermatology clinic in Egypt. Viral skin infections were more prevalent among patients who lived in rural areas and under crowded conditions. These data may have important public health implications particularly in developing countries.
13
Sun, Fengwu, Eiichi Egami, Pablo G. Pérez-González, Ian Smail, Karina I. Caputi, Franz E. Bauer, Timothy D. Rawle, et al. "Extensive Lensing Survey of Optical and Near-infrared Dark Objects (El Sonido): HST H-faint Galaxies behind 101 Lensing Clusters." Astrophysical Journal 922, no. 2 (November 25, 2021): 114. http://dx.doi.org/10.3847/1538-4357/ac2578.
Повний текст джерелаАнотація:
Abstract We present a Spitzer/IRAC survey of H-faint (H 160 ≳ 26.4, < 5σ) sources in 101 lensing cluster fields. Across a CANDELS/Wide-like survey area of ∼648 arcmin2 (effectively ∼221 arcmin2 in the source plane), we have securely discovered 53 sources in the IRAC Channel-2 band (CH2, 4.5 μm; median CH2 = 22.46 ± 0.11 AB mag) that lack robust HST/WFC3-IR F160W counterparts. The most remarkable source in our sample, namely ES-009 in the field of Abell 2813, is the brightest H-faint galaxy at 4.5 μm known so far (CH2 = 20.48 ± 0.03 AB mag). We show that the H-faint sources in our sample are massive (median M star = 1010.3±0.3 M ⊙), star-forming (median star formation rate = 100 − 40 + 60 M ⊙ yr−1), and dust-obscured (A V = 2.6 ± 0.3) galaxies around a median photometric redshift of z = 3.9 ± 0.4. The stellar continua of 14 H-faint galaxies can be resolved in the CH2 band, suggesting a median circularized effective radius (R e,circ; lensing corrected) of 1.9 ± 0.2 kpc and <1.5 kpc for the resolved and whole samples, respectively. This is consistent with the sizes of massive unobscured galaxies at z ∼ 4, indicating that H-faint galaxies represent the dusty tail of the distribution of a wider galaxy population. Comparing with the ALMA dust continuum sizes of similar galaxies reported previously, we conclude that the heavy dust obscuration in H-faint galaxies is related to the compactness of both stellar and dust continua (R e,circ ∼ 1 kpc). These H-faint galaxies make up 16 − 7 + 13 % of the galaxies in the stellar-mass range of 1010 − 1011.2 M ⊙ at z = 3 ∼ 5, contributing to 8 − 4 + 8 % of the cosmic star formation rate density in this epoch and likely tracing the early phase of massive galaxy formation.
14
Martin, Brian J., Martin J. MacInnis, Jenna B. Gillen, Lauren E. Skelly, and Martin J. Gibala. "Short-term green tea extract supplementation attenuates the postprandial blood glucose and insulin response following exercise in overweight men." Applied Physiology, Nutrition, and Metabolism 41, no. 10 (October 2016): 1057–63. http://dx.doi.org/10.1139/apnm-2016-0169.
Повний текст джерелаАнотація:
Green tea extract (GTE) ingestion improves glucose homeostasis in healthy and diabetic humans, but the interactive effect of GTE and exercise is unknown. The present study examined the effect of short-term GTE supplementation on the glycemic response to an oral glucose load at rest and following an acute bout of exercise, as well as substrate oxidation during exercise. Eleven sedentary, overweight men with fasting plasma glucose (FPG) ≥5.6 mmol·L−1 (age, 34 ± 13 years; body mass index = 32 ± 5 kg·m−2; FPG = 6.8 ± 1.0; mean ± SD) ingested GTE (3× per day, 1050 mg·day–1 total) or placebo (PLA) for 7 days in a double-blind, crossover design. The effects of a 75-g glucose drink were assessed on 4 occasions during both GTE and PLA treatments: On days 1 and 5 at rest, and again following an acute bout of exercise on days 3 and 8. The glycemic response was assessed via an indwelling continuous glucose monitor (CGM) and venous blood draws. At rest, 1-h CGM glucose area under the curve was not different (P > 0.05), but the postexercise response was lower after GTE versus PLA (330 ± 53 and 393 ± 65 mmol·L−1·min−1, main effect of treatment, P < 0.05). The 1-h postprandial peaks in venous blood glucose (8.6 ± 1.6 and 9.8 ± 2.2 mmol·L−1) and insulin (96 ± 59 and 124 ± 68 μIU·ml−1) were also lower postexercise with GTE versus PLA (time × treatment interactions, P < 0.05). In conclusion, short-term GTE supplementation did not affect postprandial glucose at rest; however, GTE was associated with an attenuated glycemic response following a postexercise oral glucose load. These data suggest that GTE might alter skeletal muscle glucose uptake in humans.
15
Bichha, R. P., K. K. Jha, V. S. Salhotra, A. P. Weerakoon, K. B. Karki, and Navneet Bichha. "An Epidemiological Study to Find out Risk Factors of Multi Drugs Resistance Tuberculosis in Nepal." SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS 14, no. 2 (March 13, 2018): 31–38. http://dx.doi.org/10.3126/saarctb.v14i2.19335.
Повний текст джерелаАнотація:
Introduction: Drug resistant tuberculosis is a threat to tuberculosis control worldwide. Previous anti- tuberculosis treatment is a widely reported risk factor for multi drug resistant tuberculosis (MDR-TB), whereas other risk factors are less well described. In Nepal National Tuberculosis Control Programme initiated DOTSPLUS Pilot project from September 2005 using standardized treatment regimen.Objective: To explore the risk factors for MDR-TB in Nepal.Methodology: Institution based matched case control study with a case: control ratio of 1:2 was carried out in three regions of Nepal. Fifty five cases and 110 controls were selected. Current MDR-TB patients on treatment from DOTS–Plus clinic were enrolled as cases. Controls were age, sex matched cured TB patients and who had completed treatment either from the same centre or any DOTS Centre adjacent to that DOTS Plus Centre. Data was collected by a trained research assistant using interviewer administered structured questionnaire. Matched analysis was done using SPSS 16 version. Confounding effects were controlled by using matching, matched analysis and regression analysis.Results: In matched analysis following were the significant risk factors for MDR-TB in Nepal.(1) HIV Sero positivity (OR 15.9, CI 1.9- 133.0) (2) Travel cost more than 50 NRs per day (OR 6.5, CI 2.4- 9.8) (3) Contact history of TB (OR 3.8, CI 2.2- 6.6) (4) Living in a nuclear family (OR 6.0, CI 2.6- 13.9)(5) Non adherence to DOTS (OR 18.6, CI 2.27- 151.0) (6) Distance to treatment centre more than 5 Km ( OR 3.9, CI 1.5- 10.) (7) Previous history of TB ( OR 12.0, CI 5.4 -26.5)(8) Living in a rural area (OR 4, CI 2.1- 8.5) (9) Unmarried (Crude OR 3.3,CI 1.6- 6.8) (10) Un-employment (OR 3.4,CI 1.6-7.6)(11) Living in a rented house (OR 3.5, CI 1.77- 3.67) (12) Single bed room (OR 2.8, CI 1.13- 6.9). Using muti-variate analysis except living in a rented house and single bed room other variables were positive significant predictors for MDR –TB in Nepal.Conclusions: Many risk factors were related to the DOTS. Strengthening of DOTS programme to tackle the identified risk factors can reduce the MDR –TB burden in Nepal.SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS, Vol. 14, No. 2, 2017, Page: 31-38
16
Jain, Punit, Prashant Deshpande, Anu Korula, Nisham P N, Ansu Abu Alex, Fouzia NA, Kavitha Lakshmi, et al. "Adult Acute Lymphoblastic Leukemia: A Cost Effective Strategy and Limitations of Intensification of Therapy in India." Blood 126, no. 23 (December 3, 2015): 3732. http://dx.doi.org/10.1182/blood.v126.23.3732.3732.
Повний текст джерелаАнотація:
Abstract Current treatment strategies in adult acute lymphoblastic leukemia (ALL) demonstrate a long term overall survival (OS) of 30 to 54%. Improvements in OS have been attributed to increased intensification (HD-MTX), novel intensive combination therapies such as HCVAD (Kantarjian et al. JCO: 2000) and allogeneic HSCT. There is paucity of real world data, especially from developing countries on impact of such therapeutic intensifications in context of challenges such as cost of therapy, multi-drug resistant bacterial infections and poor compliance. In this retrospective study, we present the clinical and biologic risk factors, challenges and long term clinical outcomes of 507 adults with ALL (≥ 15 years) diagnosed and treated at our center from January 2004 to November 2014 using a modified GMALL protocol, as previously reported by us (Bajel et al. Leukemia: 2007). We have also described and compared the outcome of a high risk (HR) subset treated either with the intensive HCVAD regimen followed by an HSCT/maintenance therapy or the modified GMALL protocol. High risk ALL were defined as presence of any of the following 4 criteria: (i) Poor prednisolone response (peripheral blood blast count ≥1000/μL on day 8 of steroids) (ii) Cytogenetics: t(9:22) or t(4:11) (iii) Residual disease (RD) at end of induction (>5 % blasts on BM or presence of extramedullary disease) and (iv) early precursor T (ETP) cell ALL immunophenotype. All other patients were stratified as standard risk (SR). All SR cases were treated with the modified GMALL protocol. 51 (46.3%) of the HR cases with financial constraints had opted for palliation, while 59 (54.05%) of continued with the modified GMALL protocol. HR cases without financial constraints were treated with HCVAD therapy (n=53). Based on the donor availability and the patient preference for a HSCT, the HCVAD group either received 3 - 4 cycles followed by an allogeneic HSCT or 6 - 8 cycles followed by 2 years of standard maintenance. The median age was 26 years (range; 15-67 years) with 334 (65.8%) patients ≤ 35 years and 117 (23.07%) patients presenting with counts ≥ 50 x 109/L. Baseline characteristics of entire cohort has been summarized in Table 1. Four hundred thirty three patients (94.5%) achieved remission at the end of induction. Among HR subset, there was no significant difference in baseline characteristics between the groups receiving GMALL versus HCVAD. Among the HR subset, 18 (33.9%) patients in the HCVAD arm received an allogeneic HSCT. In total, there were 33 (62.2%) deaths in the HCVAD subset ± HSCT compared to 29 (49.1%) deaths in the GMALL HR arm. Among the 33 deaths in patients on the HCVAD±HSCT arm, the cause of death was; infection 17 (51.5%), relapse/progressive disease 16 (48.4%). Among the 29 deaths in the modified GMALL HR group, 24 (82.7%) deaths were due to relapse/progressive disease and 5 (17.2%) deaths due to infections. OS and event free survival (EFS) of the entire cohort is illustrated in Figure 1A and 1B. There was no significant advantage of intensifying treatment in the HR subset as illustrated in Figure 1C and 1D. The mean cost of adult GMALL protocol (excluding HSCT) was $5,100 while mean cost for HCVAD followed by maintenance/ HSCT was $30,948. This study illustrate that a modified GMALL protocol, in India, was cost effective with acceptable EFS and OS. Intensifying treatment in the HR subset did not appear to be beneficial as a result of increased treatment related mortality in this arm, which were mainly related to infections. Table 1. Baseline characteristics and of all patients with newly diagnosed ALL: Variables Patients (n = 507)n (%)/Median (range) Age in years 26 (15 - 67) Male 351 (69.2) WBC ( x 109/ L) 9.2 (0.30 - 821.4) CNS III 63 (12.4) Immunophenotype 497 (98.0) · B cell ALL 371 (74.6) · T cell ALL 126 (25.4) RT PCR 394 (77.7) · BCR ABL (+) 89 (22.6) · TEL AML (+) 8 (2.1) · MLL AF4 (+) 8 (2.1) · E2A PBX (+) 12 (3.1) Risk group · Standard risk (SR) 344 (67.9) · High risk (HR) 163 (32.1) Disclosures No relevant conflicts of interest to declare.
17
Park, Il-Kyoo, Anjali Mishra, Jason C. Chandler, and Michael A. Caligiuri. "Effective Targeting of Acute Myeloid Leukemia (AML) Harboring the FLT3 ITD Mutation through the Axl/Gas6 Pathway." Blood 116, no. 21 (November 19, 2010): 500. http://dx.doi.org/10.1182/blood.v116.21.500.500.
Повний текст джерелаАнотація:
Abstract Abstract 500 Approximately 30% of AML patients harbor activating mutant forms of Fms-like tyrosine kinase-3 (FLT3) such as internal tandem duplications (ITD). To date, targeting FLT3 ITD+ AML patients with FLT3 inhibitors has not improved outcomes, suggesting alternative strategies should be pursued. Axl is a type III receptor tyrosine kinase (RTK) which is, along with its ligand Gas6, over-expressed in AML leukemic blasts and correlated with a poor prognosis. In the present study, we asked if blocking the autocrine Axl/Gas6 pathway could impact aberrant proliferation and survival of FLT3 ITD+ AML cells. We used a soluble Axl receptor, termed Axl-Fc, to block autocrine binding of Gas6 to Axl. The FLT3 ITD+ AML cell line MV4;11 was treated with Axl-Fc in vitro for 4 days and showed a significant reduction in cell proliferation (4.1 ± 0.73 × 106 cells for isotype control (IC) Fc vs. 2.1 ± 0.56 × 106 cells for Axl-Fc, p < 0.05). This growth inhibition resulted from both G1/S cell cycle arrest (51.5 ± 9.5 % at the S phase for IC Fc vs. 2.75 ± 1.5 % for Axl-Fc, p < 0.01), as well as increased apoptosis over control (63.2 ± 8.5 % Annexin V-positive for Axl-Fc vs. 25.7 ± 4.0 % for IC Fc, p < 0.01). Axl-Fc-treated MV4;11 and primary FLT3 ITD+ AML blasts showed elevated expression of granulocyte-specific genes compared to IC Fc-treated cells ([MV4;11: lysozyme (48.6 ± 9.5-fold), myeloperoxidise (6.8 ± 0.26-fold), and elastase 2 (2.7 ± 0.45-fold); p < 0.05] [primary FLT3 ITD+ AML blasts: elastase 2 (2.4 ± 0.46-fold) and lysozyme (2.7 ± 0.56-fold); p < 0.05]). Morphological analysis showed Axl-Fc could relieve the block in myeloid differentiation for the MV4;11 AML cell line. Treatment with Axl-Fc increased the expression levels of two myeloid transcription factors in MV4;11 (C/EBPα: 16.5 ± 2.6-fold over that seen with IC Fc, p < 0.01; PU.1: 3.9 ± 0.4-fold over that seen with IC Fc, p < 0.01) and in primary FLT3 ITD+ AML blasts (C/EBPα: 2.2 ± 0.31-fold over that seen with IC Fc, p < 0.05; PU.1: 2.1 ± 0.36-fold over that seen with IC Fc, p < 0.01). A co-immunoprecipitation study demonstrated that Axl associated with phosphorylated FLT3 in MV4;11 cells. Treatment with Axl-Fc abrogated both the FLT3 phosphorylation and co-precipitation. These in vitro data suggest that the Axl/Gas6 pathway contributes to AML, at least in part, through positively regulating the phosphorylation of FLT3, and that targeting the Axl/Gas6 pathway may diminish phosphorylation of both of these RTKs in AML. In vivo, using a subcutaneous tumor xenograft model, administration of Axl-Fc into MV4;11 tumor-bearing SCID mice significantly suppressed the growth of tumor mass (0.52 ± 0.1 g for PBS-treated mice (n=7); 0.26 ± 0.04 g for IC Fc (n=7) vs. 0.08 ± 0.07 g for Axl-Fc (n=10), p < 0.01). Axl-Fc also diminished the engraftment of primary FLT3 ITD+ AML blasts into SCID mice at 8 weeks (WBC: 4.75 ± 0.59 × 106 cells per ml for IC Fc (n=4) vs. 1.6 ± 0.16 × 106 for Axl-Fc (n=5), p < 0.001; 6.9 ± 0.67 % human CD45+ cells for IC Fc vs. 2.5 ± 0.59 % for Axl-Fc, p < 0.001). Finally, we assessed Axl-Fc against the FLT3 inhibitor PKC412 (LC Laboratories, Woburn, MA). In vitro treatment of both MV4;11 and primary FLT3 ITD+ AML blasts with PKC412 induced phosphorylation of Axl and its downstream signaling molecules, such as ERK and AKT, in both. PKC412-treated MV4;11 cells harboring low level of cleaved caspase 3 (i.e., apoptotic resistant) showed a higher level of phospho-Axl, while MV4;11 cells with high level of cleaved caspase 3 possessed less phospho-Axl (39.6 ± 1.4 % phospho-Axl+ for cleaved caspase 3low population vs. 9.7 ± 3.8 % phospho-Axl+ for cleaved caspase 3high population). These results suggest that activation of the Axl/Gas6 pathway could be, at least in part, responsible for drug resistance against FLT3 inhibition. In in vivo experiment, Axl-Fc was more effective than PKC412 (75 mg/kg) at inhibiting the engraftment of primary FLT3 ITD+ AML blasts into SCID mice at 8 weeks (WBC: 2.66 ± 0.36 × 106/ml for PBS (n=5); 1.74 ± 0.19 × 106/ml for PKC412 (n=5) vs. 0.9 ± 0.11 × 106/ml for Axl-Fc (n=5), p = 0.003), while SCID mice treated with Axl-Fc plus PKC412 showed no further reduction of engraftment compared to mice treated with Axl-Fc alone. Survival studies are ongoing. In summary, our study identifies the Axl/Gas6 pathway as an important player for human FLT3 ITD+ AML cell growth and survival. Targeting the Axl/Gas6 pathway may prove as effective or superior to small molecule FLT3 inhibitors for the treatment of this subgroup of AML patients. Disclosures: No relevant conflicts of interest to declare.
18
Torres, N. F., M. C. C. Bussiere, K. S. Nogueira, D. F. Dubeibe, and C. L. M. Souza. "283 ROLE OF iNOS/NO/cGMP PATHWAY ON IN VITRO MATURATION OF BOVINE COCs CO-CULTURED WITH HEMI-SECTIONS OF FOLLICULAR WALL." Reproduction, Fertility and Development 27, no. 1 (2015): 230. http://dx.doi.org/10.1071/rdv27n1ab283.
Повний текст джерелаАнотація:
Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) works by stimulating the activity of the enzyme soluble guanylate cyclase (sGC) to synthesise cGMP, which has action in metabolism of PDE3A. Thus, NO controls the concentration of cAMP in the oocyte. The intraoocyte concentration of these cyclic nucleotides is directly linked to the control of maturation in rodents. The follicular wall hemi-sections (HS) in maturation medium partially inhibit nuclear maturation of oocytes in culture, which allows us to study the mechanism of meiosis resumption in bovines. The aim of this study is to evaluate the effect of iNOS and sGC inhibition in the nuclear maturation. Twenty cumulus-oocytes complexes (COC)/treatment were cultured with 8 HS of follicular wall at 38.5°C and 5% CO2 in 200 µL of maturation medium (TCM 199/BSA) supplemented with different concentrations of aminoguanidine (AG), iNOS inhibitor (1,10, 50, 100, and 150 mM; n = 840), and the sGC inhibitor, 1H-[1,2,4] oxadiazole-[4,3-a] quinoxalin-1-one (ODQ; 10–3, 10–4, and 10–5 nM; n = 600). The COC groups cultured in the presence (control – ve) or absence of HS (control + ve) were used as controls. The stage of nuclear maturation of oocytes was assessed by staining with 2% acetic orcein and plasma membrane integrity of cumulus cells assessed with propidium iodite (PI) and hoechst (H33342). Statistical analyses of the 6 replicates were performed by ANOVA followed by Tukey test (P < 0.05) using SAEG software (Fundação Arthur Bernardes-UFV-Viçosa, Brazil). The integrity of cumulus cells from the group of oocytes cultured without HS (control + ve; 85.9 ± 2.3%) differed from control – ve (71.2 ± 3.7%) and other treatments, 1, 10, 50, 100, and 150 mM AG, (57.8 ± 12.1; 66.3 ± 4.2; 58.2 ± 4.6; 55.3 ± 4.3; 48.3 ± 3.3, respectively; P < 0.05). The same occurred when ODQ was used, the control + ve showed the highest cellular integrity (81.1 ± 1.6), differing from the control – ve (68.1 ± 1.8) and treatment with 10–5, 10–4, and 10–3 mM ODQ (72.0 ± 2.2; 64.6 ± 4.6; 49.6 ± 6.8, respectively; P < 0.05). The presence of HS (control – ve) decreased the percentage of oocytes that reached the metaphase II (MII) in both experiments (AG and ODQ; 41.0 ± 4.0; 39.1 ± 1.7, respectively) compared to control + ve (78.5 ± 3.9; 71.9 ± 16.6, respectively; P < 0.05). The addition of 100 and 150 mM AG inhibited the resumption of meiosis and progression to MII compared with other concentrations of AG and the controls + ve and – ve. The addition of ODQ stimulated resumption of meiosis, but at the concentration 10–3 nM there was a decrease in the number of COC that reached MII (21.8 ± 3.4) compared to control + ve (71.9 ± 16.6) and – ve (39.1 ± 1.7) and the other treatments (10–4 and 10–5 nM; 33.0 ± 1.8; 35.7 ± 2.5, respectively; P < 0,05). Using the model of in vitro maturation in which partial inhibition of meiosis resumption occurs, the results of this experiment show that (1) the iNOS/NO/cGMP pathway modulates plasma membrane integrity of cumulus cells and (2) that the activity of iNOS/NO pathway is important for the maintenance of the COC at the stage of germinal vesicle (GV) and progression of meiosis to MII.The authors acknowledge FAPERJ E-26/103.080/2011 for financial support.
19
Wang, Xiaoli, Sonam Prakash, Min Lu, Yan Li, Attilio Orazi, and Ronald Hoffman. "Characterization of Splenic CD34+ Cells From Patients with Primary Myelofibrosis." Blood 118, no. 21 (November 18, 2011): 2810. http://dx.doi.org/10.1182/blood.v118.21.2810.2810.
Повний текст джерелаАнотація:
Abstract Abstract 2810 Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by abnormal trafficking of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC), resulting in their constitutive mobilization and the establishment of extramedullary hematopoiesis. The mechanism by which HSC/HPC preferentially migrate, reside, proliferate and differentiate in the spleen remains poorly understood. We phenotypically and functionally characterized PMF splenic CD34+ cells (PMFSC) (n=8). Greater numbers of CD34+ (5.9±1.9%), CD34+CD38- (3.2±1.6%), CD34+CD90+ (2.0±1.5%), CD34+Lin- (4.4±1.8%) cells and assayable HPCs (4513±240/106 mononuclear cells (MNC)) were detected in PMF spleens as compared with PMF peripheral blood (PB) (CD34+: 1.4±0.6%; CD34+CD38-: 0.8±0.6%; CD34+CD90+: 0.1±0%; CD34+Lin-: 0.8±0.4%; HPC: 2496±677/106 MNCs). In addition, the expression of CXCR4 by CD34+ cells present in the spleen (20.8±3.7%) was shown to be greater than that previously observed in PMF PB CD34+ cells (PMFPBC) (7.4±2.2%, P<0.05). We next examined PMF spleens for the presence of SCID repopulating cells by analyzing human cells in the marrow and spleen of NOD/SCID γcnull mice transplanted with PMFSC using flow cytometry. Five months following transplantation, 12.1% of the marrow cells were hCD45+ in mice receiving 2×105 PMFSC as compared to 3.4% in mice receiving same number of PMFPBC from the same patient. The percentage of hCD45+ cells in the marrow significantly increased to 40.6% in mice receiving 2×106 PMFSC, while 2.7% hCD45+ cells were detected in the marrow of mice receiving similar number of PMFPBC. Surprisingly, 0.6% of the cells were hCD45+ in the spleens of mice receiving 2×104 PMFSC, while 33.9% of the cells were hCD45+ in the spleens of mice receiving 2×105 PMFSC. By contrast, as few as 0.1% hCD45+ cells were detected in the spleens of mice transplanted with equal numbers of PMFPBC. Moreover, the spleens of mice transplanted with PMFSC contained greater number of hCD34+ cells, while no hCD34+ cells were observed in the spleens of mice transplanted with PMFPBC. The human cells in the marrow of mice receiving PMFSCs were further found to be capable of differentiating into not only myeloid cells (CD33+, 8.7%; glycophorin A+, 1.1% and CD34+, 1.3%) but also B (2.3%) and T cells (2.9%). While, the human cells in the marrow of mice receiving similar numbers of PMFPBC were composed of myeloid cells (CD33+, 0.5%; glycophorin A+, 0.1% and CD34+, 0.1%) but very few CD19+ (0.1%) and no CD3+ cells. Moreover, both myeloid cells (CD33+, 14.5%; glycophorin A+, 3.9% and CD34+, 6.8%) and CD19+ (6.7%) and CD3+ cells (23.1%) were detected in the spleens of mice receiving PMFSC. The engraftment of human cells in the spleen and marrow of mice receiving PMFSC and the distinct differentiative potential of PMFSC in mice were further confirmed by immunohistochemical analysis. Greater numbers of hCD45+ cells were observed in the marrow and spleen of mice receiving PMFSC and the degree of human cell engraftment was consistent with the number of PMFSC transplanted. Moreover, the white pulps of the spleens of mice receiving PMFSC were composed primarily of human lymphocytes. Both human granulocytic cells and human lymphocytes were observed in red pulps of the spleens of mice transplanted with PMFSC. In addition, following the infusion of 5×105 PMFSC and PMFPBC, reduced numbers of PMFSC (90.3±16.8/106 BMCs) were detected in the marrows of these mice as compared with G-CSF mobilized PB (mPB) CD34+ cells (196±19/106 BMCs; P<0.05), and the number of PMFSC that homed to the marrow of the mice was lower than PMFPBC (101.7±8.8/106 BMCs; P=0.09). By contrast, similar numbers of PMFSC and PMFPBC and mPB CD34+ cells were detected in the spleens of these mice. Recently the use of JAK2 inhibitors has been shown to dramatically reduce the size of the spleen in patients with PMF. PMFSC and PMFPBC were treated with a JAK2 inhibitor, AZD1480. Similar reductions in the number of total cells, CD34+ cells and assayable HPCs were observed as compared with cells exposed to cytokines alone. These findings suggest that multipotent HSCs are present in the spleen but not the PB of PMF patients and that PMFSC have a distinct differentiative program and migratory behavior that distinguishes them from PMF and normal PB CD34+ cells. In addition treatment with JAK2 inhibitors does not appear to lead to a reduction of splenomegly by preferentially inhibiting splenic HPCs. Disclosures: No relevant conflicts of interest to declare.
20
Antoni, Rona, Kelly L. Johnston, Adam L. Collins, and M. Denise Robertson. "Intermittentv. continuous energy restriction: differential effects on postprandial glucose and lipid metabolism following matched weight loss in overweight/obese participants." British Journal of Nutrition 119, no. 5 (March 6, 2018): 507–16. http://dx.doi.org/10.1017/s0007114517003890.
Повний текст джерелаАнотація:
AbstractThe intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (>70 %) energy restriction (ER) interspersed with normal eating. Studies to date comparing IER to continuous energy restriction (CER) have predominantly measured fasting indices of cardiometabolic risk. This study aimed to compare the effects of IER and CER on postprandial glucose and lipid metabolism following matched weight loss. In all, twenty-seven (thirteen male) overweight/obese participants (46 (sem3) years, 30·1 (sem1·0) kg/m2) who were randomised to either an IER intervention (2638 kJ for 2 d/week with an overall ER of 22 (sem0·3) %,n15) or a CER intervention (2510 kJ below requirements with overall ER of 23 (sem0·8) %) completed the study. Postprandial responses to a test meal (over 360 min) and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5 % weight loss, following a 7-d period of weight stabilisation. The study found no statistically significant difference in the time to attain a 5 % weight loss between groups (median 59 d (interquartile range (IQR) 41–80) and 73 d (IQR 48–128), respectively,P=0·246), or in body composition (P≥0·437). For postprandial measures, neither diet significantly altered glycaemia (P=0·266), whereas insulinaemia was reduced comparatively (P=0·903). The reduction in C-peptide tended (P=0·057) to be greater following IER (309 128 (sem23 268) to 247781 (sem20 709) pmol×360 min/l)v. CER (297 204 (sem25 112) to 301 655 (sem32 714) pmol×360 min/l). The relative reduction in TAG responses was greater (P=0·045) following IER (106 (sem30) to 68 (sem15) mmol×360 min/l) compared with CER (117 (sem43) to 130 (sem31) mmol×360 min/l). In conclusion, these preliminary findings highlight underlying differences between IER and CER, including a superiority of IER in reducing postprandial lipaemia, which now warrant targeted mechanistic evaluation within larger study cohorts.
21
Kutluk, M. Tezer, and Akif Yesilipek. "Pediatric cancer registry Turkey: 2009-2016 (TPOG & TPHD)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e22015-e22015. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e22015.
Повний текст джерелаАнотація:
e22015 Background: Each year 300.000 new cancer cases are expected in children & adolescents aged 0-19 years at global level. Although the long term survival rates have been improved to 85% in high income countries it is lower than this LMICs. Pediatric registries are essential for planning, evaluation, comparison for pediatric cancer care. This study focuses to pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association established a WEB based cancer registry in Turkey in 2002. The registry information for 2002-2008 was presented earlier. This study, now, is including the distribution of pediatric cancer registry for the years of 2009-2016. International Childhood Classification System was used in classification. Basic demographic findings, ICD-O-3 morphology & topography codes were recorded for each cases. Results: During the 8 years from 2009 to 2016, 13123 pediatric cancer cases were recorded. For all cases, median age was 6.5 year (0–17; M/F 7356/5759, 3 hermaphrodite). Age distribution was 0–4 yrs, 41.3%; 5–9 yrs, 24.3%; 10–14 yrs , 23.2%; 15–19 yrs, 11.0%. 7 cases older than were registered (%0.1). The distribution of tumor types were [number of cases, percentage of total, median age years, M/F]: Leukemia (3751, 28.6%, 5.5, 2148/1603); Lymphoma and other RES tumors (2381, 18.1%, 9.5, 1613/763); CNS [brain & spinal] (1672, 12.7% , 7.13, 908/764); Symphatetic system (1053, 8.0% , 2.42, 550/503); Retinoblastoma (339, 2.6%, 1.33, 188/151); Renal (675, 5.1%, 3.33, 314/361); Liver (217, 1.7% , 1.75, 116/101); Malignant bone (892, 6.8 %, 12.55, 486/406); Soft tissue sarcomas (868, 6.6% , 7.21, 518/350); Germ cell (818, 6.2%, 7.58, 292/523); Carcinoma and other malignant epithelial (391, 3.0% , 13.60, 191/200); Other/non-specific malignant (66, 0.5%, 6.54, 32/34) tumors. Five year survival rate was found as 69.5 %. Conclusions: This registry since 2002 became a critical source for health care professionals in Turkey. Survival rates for children increased from 65% to 70% based on the latest information from this study. This is compatible with Turkey’s development level as an upper middle income country. This data also allows us to use the registry information at national and international studies.
22
Li, J., M. Li, D. Wu, J. Zhou, S. O. Leung, and F. Zhang. "OP0210 EFFICACY AND SAFETY OF SM03, A RECOMBINANT ANTI-HUMAN CD22 MONOCLONAL ANTIBODY IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS: A PHASE II RANDOMIZED, DOUBLE-BLIND, MULTI-DOSE, PLACEBO-CONTROLLED STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 131.1–131. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1383.
Повний текст джерелаАнотація:
Background:Rheumatoid arthritis (RA) is a common chronic inflammatory rheumatic disease in China. SM03 is a novel chimeric monoclonal antibody (mAb) specific to the B cell restricted antigen CD22 developed for the treatment of rheumatoid arthritis (RA) and other B cell related immunological diseases.Objectives:We aim to evaluate the efficacy and safety of SM03 in patients with moderately-to-severely active RA in China.Methods:In this 24-week Phase II randomized, double-blind, multi-dose, placebo-controlled study, 156 patients were randomized with ratio of 1:1:1 to receive 3600mg cumulative dose of SM03 (group A, 600mg * 6 infusions at 0, 2, 4, 12, 14, and 16 week), 2400mg cumulative dose of SM03 (group B, 600mg*4 infusions at 0, 2, 12, and 14 week) and placebo (group C). All patients remained on background treatment of MTX. Efficacy and safety were assessed at weeks 4, 8, 12,16 and 24.The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 24.Safety profile was also assessed.Results:ACR20 response rates at 24-week were significant for group A (65.3%, p=0.002) and B (56.9 %, p=0.024) versus group C (34.0%). There is no significant difference in ACR20 between group A and B(Table 1 & Fig 1). We did not observe significant difference in any adverse event (AE) among group A (35.3%), B (51.9%) and C (34.6%)(Table 2). In groups A and B, 13 (12.6%) patients reported treatment-related infection, and 5 (6.8%) patients were positive in anti-drug antibodies analysis. In group A (higher dose), 3.9% patient had AE of treatment-related infections. No patients reported treatment-related severe infection or any malignancies caused by treatment in groups A and B.Table 1.Summary of ACR/DAS EULAR Responses of Patients with RA to SM03 at Week 24ResponseGroup CPlacebo+MTX(n=47)Group A SM03600mg*6+MTX(n=49)Group B SM03600mg*4 +MTX(n=51)ACR 2034.0%65.3% *56.9% *ACR 5017.0%44.9%**29.4%ACR 704.3%18.4%***9.8%EULAR response good & moderate40.4%75.5%^70.6%^EULAR response good12.8%30.6%^^15.7%Change of DAS28 from baseline-0.70-1.65^^^-1.38^^^DAS28≤3.214.9%30.6%19.6%DAS28<2.68.5%18.4%5.9%Compared with group C(Placebo), results of group A and B were shown respectively*P=0.002, P=0.024; **P= 0.003; ***P= 0.03;^ P<0.001, P=0.003; ^^ P=0.034; ^^^P=0.008, P=0.047Table 2.Profile of Adverse EventsAdverse event, N (%)Group C(N=52)Group A(N=51)Group B(N=52)Any AE18(34.6)18(35.3)27(51.9)AE-drug related7(13.5)5(9.8)8(15.4)AE-mild16 (30.8)15(29.4)24(46.2)AE-moderate2(3.8)2(3.9)3(5.8)AE-severe-1(2.0)-AE-leading to discontinuation-2(3.9)-Serious adverse event, SAE1(1.9)1(2.0)-AE-1stcycle(week 0-12)151322AE-2ndcycle(week 12-24)9914Fig 1.Percent of Patients Achieving ACR 20 Response by VisitConclusion:In Chinese patients with active RA, both 2400mg and 3600mg cumulative doseof SM03,in combination with MTX were efficacious and well tolerated. throughout the 24 weeks of treatment.Moreover, SM03 has demonstrated a good safety profile, especially in terms of treatment-related infection, malignancy and immunogenicity.References:NoneDisclosure of Interests:None declared
23
Siraj, Abdul K., Rong Bu, Maha Al-Rasheed, Muna Ibrahim, Prashant Bavi, Jehad Abubaker, Naif Al-Jomah, et al. "Association between Drug-Metabolizing Enzymes Polymorphisms and Diffuse Large B-Cell Lymphoma Risk in the Middle Eastern Population." Blood 108, no. 11 (November 1, 2006): 2043. http://dx.doi.org/10.1182/blood.v108.11.2043.2043.
Повний текст джерелаАнотація:
Abstract The last four decades have seen significant increase in the incidence of non-Hodgkin’s lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogens exposure related cancer risk and xenobiotic gene polymorphisms. We have undertaken a case control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1 and NQO1) were characterized in 187 individuals with DLBCL and 513 normal controls using polymerase chain reaction (PCR) based method. We chose the Saudi population as our study population because of its high consanguinity and its relative genetic homogeneity. The CYP1A1*2C, GSTT1 null and GSTP1 TT genotype were all found to be significant predictors of DLBCL risk (odds ratio 6.62, 11.94 and 3.42 respectively). None of the other alleles tested for proved to be significant indicators of DLBCL risk. These results suggest that the risk of DLBCL may indeed be associated with xenobiotics - metabolism and thus with environmental exposures. Table 1 Distribution of polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p OR CYP1A1 −/− 384(76.5%) 104(78.8%) *2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 2A allele 13% 11.36% 0.659 0.839 CYP1A1 −/− 443(88.2%) 121(91.66%) *2B −/2B 50(10%) 10(7.58%) 0.505 0.732 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 2B allele 6.8% 4.55% 0.424 0.646 CYP1A1 −/− 497(99%) 125(94.7%) *2C −/2C 5(1%) 4(3.03%) 0.090 3.181 2C/2C 0 3(2.27%) 0.008 ND 2C allele 0.5% 3.8% 0.011 6.627 NQO1 C609T CC 295 (58.5%) 94 (62.7%) CT 177 (35.1%) 37 (24.7%) 0.051 0.656 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 GSTP1 2293 CC 389 (76.3%) 113 (77.9%) CT 113 (22.2%) 24 (16.6%) 0.240 0.731 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 GSTP1 A1578G AA 170 (33.5%) 56 (35%) AG 271 (53.5%) 96 (60%) 0.772 1.075 GG 66 (13%) 8 (5%) 0.013 0.368 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 GSTT1 P 385 (75%) 36 (20.1%) D 128 (25%) 143 (79.9%) <0.001 11.948 GSTM1 P 233 (45.4%) 91 (50%) D 280 (54.6%) 91 (50%) 0.300 0.832 Table 2 Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group. Genotype Control Case p OR Null: Complete deletion of GSTT1 and GSTM1 allele Present 423 (82.8%) 109 (60.9%) Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087
24
Magnus, Dan, Santosh Bhatta, and Julie Mytton. "432 Establishing injury surveillance in emergency departments in Nepal: epidemiology and burden of paediatric injuries." Emergency Medicine Journal 37, no. 12 (November 23, 2020): 825.2–827. http://dx.doi.org/10.1136/emj-2020-rcemabstracts.7.
Повний текст джерелаАнотація:
Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)
25
Cappellini, Maria Domenica, Elliott Vichinsky, Renzo Galanello, Antonio Piga, Paul Williamson, and John B. Porter. "Long-Term Treatment with Deferasirox (Exjade®, ICL670), a Once-Daily Oral Iron Chelator, Is Effective in Patients with Transfusion-Dependent Anemias." Blood 110, no. 11 (November 16, 2007): 2777. http://dx.doi.org/10.1182/blood.v110.11.2777.2777.
Повний текст джерелаАнотація:
Abstract Background: The efficacy and safety of deferasirox was established during five 1-year core trials. As many patients will require lifelong chelation therapy, assessing long-term efficacy and safety is important. In the core trials, initial doses were assigned by baseline liver iron concentration (LIC). A clear dose response was observed: 5/10 mg/kg/d doses were generally insufficient to balance iron intake from ongoing transfusions, while 20 and 30 mg/kg/d maintained or reduced iron balance, respectively. This analysis evaluates serum ferritin (SF) levels and cumulative safety data during 4-year extension trials. Methods: In the extensions, dose modifications were based on safety and efficacy parameters. Safety and SF were assessed monthly. Due to methodological differences in study 105, the SF data from this trial are not included in this analysis. Results: 1034 patients with β-thalassemia (n=750), sickle cell disease (n=185), MDS (n=47) and other anemias (n=52) have received deferasirox. 703 patients received deferasirox in the core trials and have been on treatment for a median of 3.4 years; 331 crossed over to deferasirox in the extensions. 210 (20%) patients have discontinued treatment due to: AEs (74), consent withdrawal (64), unsatisfactory therapeutic effect (29) and other (43). Only 17 (1.6%) patients have discontinued in the past 12 months (9 AEs; 1 death; 4 lost to follow-up; 2 withdrew consent; 1 other). 16 patients have died, 6 in the core and 10 in the extensions. 5 patients (4 β-thalassemia, 1 sideroblastic anemia) aged 18-24 years with inadequate chelation and severe iron overload before study entry died with cardiac failure in the extensions. Other deaths were due to other complications/progression of the underlying disease. At month 42, mean (SD) dose in the 5/10, 20 and 30 mg/kg/d dose groups was 21.8 (9.3), 23.2 (8.2) and 25.4 (9.8) mg/kg/d, respectively. Median SF levels (ng/mL) are shown in the Table (n=652, deferasirox cohort only). Drug-related AEs during deferasirox treatment were generally transient, of mild/moderate severity, and showed a reduction in frequency from the core trials. No patient has developed progressive increases in serum creatinine or values >2 x ULN. 2 patients discontinued due to stable creatinine increases of 1.5 x ULN and confounding circumstances (concomitant cyclosporine and multiple infections, respectively). 1 patient discontinued due to recurrent episodes of proteinuria. 12 patients discontinued due to increases in transaminases (4 core study, 8 extension [3 crossover patients]). Drug-induced liver toxicity was likely in 2 patients with early onset and positive rechallenge. Increasing LIC due to under-chelation was the likely explanation in at least some patients. Conclusions: Over 3.5 years’ treatment, deferasirox 20/30 mg/kg/d maintained/reduced SF levels in patients with various transfusion-dependent anemias. There was no increase in frequency of drug-related AEs or changes in markers of liver or renal function that differed significantly from the 1-year core trials. Initial dose, mg/kg/d *Dose adjustments Month 5/10 (n=227) 20 (n=182) 30 (n=243) Baseline 2051 2375 3734 12* 2650 2161 2649 24 2481 2508 2271 36 1439 1844 2071 42 1345 1667 2025
26
Sadaf Rizwan, Aesha, Bushra Mehmood, and Shahzadi Hannan Arshad. "Compare the Outcomes of Subcutaneous Drains versus No Drains in Patients with Repeated Cesarean Section." Pakistan Journal of Medical and Health Sciences 15, no. 9 (September 30, 2021): 2579–81. http://dx.doi.org/10.53350/pjmhs211592579.
Повний текст джерелаАнотація:
Objective: The aim of this study is to compare the outcomes of subcutaneous drains versus no drains in patients with repeated cesarean section. Study Design: Randomized control trial Place and Duration: Conducted at Gyne & Obs Department, Shahida Islam Teaching Hospital Lodhran, during from 8-01-2020 to 8-08-2020. Methods: Total 90 pregnant women with repeated cesarean section were presented in this study. Patients were aged between 22-50 years. Detailed demographics of enrolled cases including age, body mass index, gestational age and parity were recorded after taking informed written consent. Patients were categorized into two groups, group I had 45 patients with subcutaneous drain and 45 patients of group II were without drain. Post-operative outcomes were assessed and compared among both groups. VAS was used to compare pain among both groups. SPSS 22.0 version was used to analyze the data. Results: Mean age of the patient in group I was 30.6±8.44 years with mean BMI 33.08±5.26 kg/m2 but in group II mean age was 29.03±7.37 years with mean BMI 31.12±11.58 kg/m2. Mean gestational age in group I was 37.9±3.9 weeks and in group II mean gestational age was 37.3±2.7 weeks. There was no any significantly difference in parity among both groups. Post-operative mean haemoglobin in group I was lower 7.9±1.6 gm% as compared to group II 8.11±0.4 gm%. Mean pain score in group I was 6.8±4.7 and in group II was 8.2±4.11. Prevalence of wound infection was greater in group II 5 (11.1%) as compared to group I 3 (6.7%). Hospital stay was shorter in group I 9.7±2.11 days as compared to group II 10.8±1.14 days. Frequency of superficial SSI and wound seroma were significantly higher among patients of group II. Conclusion: In this study we concluded that those patients who received subcutaneous drain undergoing cesarean section resulted low post-operative pain with fewer chances of wound infection as compared to the patients undergoing C-section without drain. Except this frequency of SSI and hospital stay was shorter among patients of drain group. Keywords: Cesarean, Drain, Wound Infection, Superficial Surgical Site Infection, Pregnant Women
27
De Hooge, M., A. Ishchenko, S. Steinfeld, A. Nzeusseu Toukap, D. Elewaut, H. Leroi, R. Lories, K. De Vlam, and F. Van den Bosch. "OP0055 MINIMAL RADIOGRAPHIC DAMAGE OF SACROILIAC JOINTS DETECTED IN PSORIATIC ARTHRITIS PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 37.1–37. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2392.
Повний текст джерелаАнотація:
Background:Psoriatic arthritis (PsA) is an inflammatory joint disease that is traditionally included in the Spondyloarthritis (SpA) spectrum. Prevalence and impact of axial involvement in PsA remains understudied but increasingly affects treatment decisions.Objectives:The first step, in this multi-purpose radiographic study, is to report on baseline radiographic damage of the sacroiliac joints (SIJ) in PsA patients from a prospective multicentre cohort study in private and academic rheumatology practices.Methods:Data from the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS), a prospective multicentre cohort involving 17 Belgian rheumatology practices. Recruitment was from December 2012 until July 2014. Patients were included in the study when the local rheumatologist could diagnose an existing or new PsA and when patients fulfilled the Classification criteria for Psoriatic Arthritis (CASPAR). Radiographs of the SIJ were obtained at baseline and after 2 years. Two calibrated readers assessed radiographic damage by grading the SIJ according to the modified New York (mNY) criteria. When assessing the images, readers were blinded for clinical data and information from other obtained images (radiographs of the hands, feet and spine). Individual scores as well as consensus scores are described.Results:In total 461 patients where included in BEPAS. Mean age was 52.79±12.29 years and 43.0% (n=198) were female; average disease duration was 8.5 ± 9.3 yrs and approximately 34% of the patients report inflammatory axial pain. From 338 patients SIJ radiographs were obtained. At baseline, the vast majority of patients did not fulfil the mNY criteria (n=325, 96.2%), according to both readers. In 8 cases (2.4%) there was concordance on fulfilment of the mNY criteria. Discordant cases (n=5, 1.4%) were equally distributed. Agreement between the 2 readers was good with 98.5% overall agreement and kappa=0.75. Therefore, with a more sensitive approach (any of the 2 readers scores mNY positive) we see slight differences; 13 patients (3.8%) fulfil the mNY criteria. Table 1 shows radiographic damage by individual readersTable.Baseline data on radiographic damage of the sacroiliac joints in Belgian patients with newly diagnosed or existing PsA included in the BEPAS.N=338Right sacroiliac jointLeft sacroiliac jointGradesType of lesionReader 1Reader 2Reader 1Reader 20No abnormalities298 (88.2%)301 (89.1%)298 (88.2%)296 (87.6%)1Indefinite abnormalities32 (9.5%)23 (6.8%)27 (8.0%)23 (6.8%)2-3Abnormalities5 (1.5%)12 (3.6%)9 (2.7%)19 (5.6%)Erosion3 (0.9%)11 (3.3%)4 (1.2%)18 (5.3%)Sclerosis4 (1.2%)12 (3.6%)5 (1.5%)13 (3.9%)Joint space alteration (narrowing or widening)1 (0.3%)1 (0.3%)4 (1.2%)2 (0.6%)Partial ankylosis2 (0.6%)3 (0.9%)5 (1.5%)8 (2.4%)4Total ankylosis3 (0.9%)2 (0.6%)4 (1.2%)-In 128 patients (37.9%) a follow-up x-ray after 2 years was available. In 124 patients (96.9%) there was reader agreement on mNY negative status. There was disagreement between readers on a positive mNY in 2 patients (equally distributed) and agreement on 2 patients (1.6%). There were no patients with consensus between readers on the change in mNY over 2 years, but 1 reader reported 1 patient becoming mNY positive after 2 years.Conclusion:Despite the patient self-identified presence of axial disease in up to 34% in this cohort of PsA patients, there was minimal radiographic damage on SIJ, suggesting that SIJ disease is not a major manifestation of PsA.Disclosure of Interests:Manouk de Hooge: None declared, Alla Ishchenko: None declared, Serge Steinfeld: None declared, Adrien Nzeusseu Toukap Grant/research support from: AbbVie, Celgene Corporation, Janssen, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, UCB – consultant, Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, UCB – advisory board member, Dirk Elewaut: None declared, Hermine Leroi Employee of: MSD Belgium, Rik Lories Grant/research support from: AbbVie, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Samumed and UCB – grant/research support (on behalf of Leuven Research and Development), Consultant of: AbbVie, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Samumed and UCB – consultant (on behalf of Leuven Research and Development), Speakers bureau: AbbVie, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Samumed and UCB – speaker (on behalf of Leuven Research and Development), Kurt de Vlam Grant/research support from: Celgene, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Eli Lilly, Galapagos, Johnson & Johnson, Novartis, Pfizer Inc, UCB, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB
28
Hwang, Sang Mee, Sang-ho Lee, Seong_Ho Kang, Seonyang Park, Sung-Soo Yoon, Byoung Kook Kim, Hyun Kyung Kim, Han Ik Cho, and Dong Soon Lee. "Is Acute Erythroid Leukemia a Transitional Stage from MDS to AML?: A Study by Fluorescence in Situ Hybridization and Cytogenetics." Blood 112, no. 11 (November 16, 2008): 4867. http://dx.doi.org/10.1182/blood.v112.11.4867.4867.
Повний текст джерелаАнотація:
Abstract Background: Chromosomal abnormalities of acute erythroid leukemia (AEL) are reported to be complex and nonspecific. We compared the cytogenetic abnormalities of AEL to other subtypes of acute myeloid leukemia (AML) by G- band karyotyping and fluorescence in situ hybridization (FISH) techinique using 18 probes. Methods: 384 patients diagnosed with AML between January 2000 and December 2007 were classified morphologically by French-American-British classification. G-band karyotyping and FISH for 4 recurrent chromosomal abnormalities in AML [AML/ETO rearrangement, PML/RARa rearrangement, MLL rearrangement, inv(16)] were performed. To verify whether common cytogenetic abnormalities of myelodysplastic syndrome (MDS) were present in AEL, FISH for 5q deletion, 7q deletion, trisomy 8 and gain of 1q were performed on bone marrow nucleated cells of 25 patients with AEL. To evaluate the numerical chromosomal changes, ten additional FISH tests were done. Chromosomal enumeration probes (CEP) were primarily used and in case where there were no CEP available, probes for chromosomal rearrangement were surrogately used. Results: Incidence of recurrent genetic changes of AML [AML/ETO, PML/RARA, MLL, inv(16)] was 0% in AEL, while the incidence of AML/ETO, PML/RARA, MLL and inv(16) rearrangement in AML excluding AEL was 12.8%, 12.7%, 5.0%, 4.6%, respectively. Frequencies of numerical chromosomal changes were 11.8% in AML excluding AEL and 44% in AEL, showing significantly higher incidence of numerical changes in AEL. Frequencies of cytogenetic changes, which are common in MDS, were 20% for 5q deletion, 32% for trisomy 8, 16% for 1q gain among AEL patients. In total, 40% of the AEL patients showed similar chromosomal changes to MDS. By G-banding, 32% of the AEL patients showed numerical change of chromosome 8 and 20% for chromosome 5. However, numerical chromosomal changes by G-banding were not statistically different between AEL and other AML, while >3 complex chromosomal changes were significantly higher in AEL. (P=0.001) Out of 25 AEL patients, 4 patients (16%) were transformed from MDS and 1 patient (4%) transformed to other subtype of AML during treatment. Discussions: Numerical chromosomal change was the most predominant genetic change of AEL, while recurrent genetic changes of AML were not found in AEL. Instead, AEL patients showed similar chromosomal changes to MDS. This implies that AEL subtype of AML is rather a separate disease entity from the other types of AML, more within the spectrum of MDS. We infer that AEL is a transitional stage from MDS to AML. Table 1. General aspects and the summary of the results of AML and AEL* Characteristics AML AEL Abbreviations: AML, Acute myeloid leukemia; FAB, French-American-British classification; AEL, acute erythroid leukemia * AEL diagnosed by WHO criteria ¢” FISH was done on available specimen only ¢Ô Ploidy changes were determined by 18 kinds of probes in AEL, and 4 kinds of Probes in AML subtypes excluding AEL Gender female 161 41.9% 6 22.2% male 223 58.1% 21 77.8% total 384 100.0% 27 100.0% FAB classification M0 16 4.2% M1 43 11.2% M2 124 32.3% M3 43 11.2% M4 81 21.2% M5 17 4.4% M6 27 7.0% M7 7 1.8% undetermined 26 6.8% AML excluding AEL AEL Age, years (median) 15–77 (51) 17–84 (60) <60 248 69.5% 11 40.7% °Ã60 109 30.5% 16 59.3% Recurrent genetic abnormalities ¢” PML/RARA 43/338 12.7% 0/27 0.0% AML/ETO 42/327 12.8% 0/27 0.0% inv(16) 12/259 4.6% 0/27 0.0% MLL 16/319 5.0% 0/27 0.0% Abnormal karyotype 85/356 23.9% 13/27 48.1% Ploidy change by FISH ¢Ô 41/348 11.8% 14/25 56.0%
29
Iqbal, S., D. Yang, S. Cole, A. B. El-Khoueiry, W. Boswell, R. Agafitei, R. Lujan, and H. J. Lenz. "Phase II study of capecitabine and gemcitabine in patients with metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e15077-e15077. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15077.
Повний текст джерелаАнотація:
e15077 Background: Failing standard chemotherapy, many mCRC patients (pts) maintain an adequate performance status necessitating therapeutic options. Preclinical data in CRC cell lines shows that 5-FU and gemcitabine have synergistic cytotoxicity by stabilization of thymidylate synthase resulting in stronger inhibition of DNA synthesis. Methods: The primary objective was to assess time to progression (TTP) in mCRC pts who had progressed on irinotecan and oxaliplatin therapy. Secondary objectives included response rate (RR), overall survival (OS), toxicity and correlates to assess genes in the 5-FU, gemcitabine pathways. This single center study was a two stage minimax design. A ≤ 30% chance of progressing within the first 6 weeks would be promising. 27 pts were enrolled in the first stage, if ≥ 13 progressed (or had unacceptable toxicity) prior to 6 weeks then the study would be terminated. The planned sample size was 53 pts. A cycle was defined as capecitabine 650 mg/m2 BID days 1–14 and gemcitabine 1,000 mg/m2 i.v. over 100 minutes days 1, 8. Results: The study met its first stage goal and continued to accrue 54 eligible pts (male 24/female 30), median age 58 years (range 31–78). Pts received a median of 2 cycles (range 1–19), with 22% of pts receiving 6 + cycles. Three pts that withdrew shortly after start were excluded from toxicity analysis. Of 51 pts, 23 had Grade 3/4 drug related toxicity, commonly 9 pts ANC/AGC; 4 pts pain. The probability of progressing at 6 weeks was .46 + .07, with 23 pts progressing or dying within that time. Median OS was 5.9 months (95% CI 4.3, 8.7), PFS was 8.1 weeks (95% CI 5.6, 11.6). Of 48 pts evaluable for response, 17 had stable disease, for these pts, the median PFS was 4.3 months (95%CI: 3.9–8.8) and OS 10 months (95%CI: 7.9–16.6); 31 had progressive disease or symptomatic deterioration. Conclusions: The combination of gemcitabine and capecitabine in refractory mCRC was well tolerated. Unfortunately, the study did not meet the primary endpoint, but there appears to be a subset of pts with stable disease who may benefit from therapy. Correlatives are pending. [Table: see text]
30
Rodeghiero, Francesco, Andrew Provan, Michael Steurer, Bertrand Godeau, Nancy Carpenter, and Georg Kreuzbauer. "Pooled Analysis of Safety and Efficacy of Romiplostim in Splenectomized and Nonsplenectomized Patients (pts) with Immune Thrombocytopenia (ITP)." Blood 124, no. 21 (December 6, 2014): 4199. http://dx.doi.org/10.1182/blood.v124.21.4199.4199.
Повний текст джерелаАнотація:
Abstract Introduction: Romiplostim is a thrombopoietin receptor agonist approved for use in adult pts with ITP. Pooled analyses of combined pt data from romiplostim ITP clinical studies have previously been reported. Here we report updated safety and efficacy data according to baseline splenectomy status. Methods: Data from adult pts in 13 completed ITP studies with romiplostim were analysed up to June 2014. Pts received romiplostim, placebo or medical standard of care (SOC) and data from the placebo/SOC arms were pooled. All 13 studies were included in analyses of baseline pt characteristics and safety endpoints; 4 early dose-finding studies were excluded from analyses of efficacy endpoints as they do not reflect the current dosing of romiplostim. Adverse events were adjusted for time spent on study and reported as rates per 100 pt-years. For pts who started their parent study in the placebo/SOC group and then went on to receive romiplostim in an extension study, all data from the first dose of romiplostim were included in the romiplostim group. A platelet response was defined as a platelet count ≥50x109/L without rescue medication in the previous 8 weeks; a platelet response for 9 out of any 12 consecutive weeks on-study was considered a sustained platelet response. All analyses were descriptive and no statistical testing was performed. Results: Data from 1,111 pts were analysed, 395 splenectomized and 716 nonsplenectomized. The splenectomized and nonsplenectomized groups were similar in age (median 52 vs 53 years) and sex (female 64% vs 60%), but in the splenectomized group median baseline platelet counts were slightly lower (14 vs 19x109/L) and a higher proportion of pts were known to have received >3 prior ITP treatments (38% vs 12%) than the nonsplenectomized group. Rates of AEs, serious AEs, fatal AEs, treatment-related AEs, thrombotic events, and hemorrhages were lower in nonsplenectomized than splenectomized pts and were in general lower in romiplostim than placebo/SOC-treated pts in both groups. Bone marrow reticulin occurred in 17 romiplostim-treated pts and one placebo-treated pt, at a slightly increased rate in splenectomized vs nonsplenectomized pts. Bone marrow collagen was reported in one romiplostim-treated nonsplenectomised pt. Data from 1,024 pts were analysed for efficacy (376 splenectomized, 648 nonsplenectomized). The median (Q1, Q3) most frequent weekly dose was 4 µg/kg (2, 9) in splenectomized and 3 µg/kg (2, 7) in nonsplenectomized pts. A platelet response was achieved in 82% of splenectomized and 91% of nonsplenectomized pts and a sustained platelet response in 66% and 79%, respectively. The median time to first response was 2.1 weeks for splenectomized and 2.0 weeks for nonsplenectomized pts. Platelet responses were maintained in those who responded: after the first response the median (Q1, Q3) proportion of time with a response was 97% (79%, 100%) for splenectomized and 100% (91%, 100%) for nonsplenectomized pts. Conclusions: A relatively large number of nonsplenectomized pts have received romiplostim in clinical studies. Safety of romiplostim was comparable in splenectomized and nonsplenectomized patients with no new safety signals observed, and platelet response rates were high and of sustained duration in both groups. Abstract 4199. Table Number of events (rate per 100 pt-years) Splenectomized Nonsplenectomized Placebo/SOC N=27 Pt-yr=11.2 Romiplostim N=391 Pt-yr=702.0 Placebo/SOC N=106 Pt-yr=97.7 Romiplostim N=655 Pt-yr=1129.7 All AE 208 (1861.1) 8609 (1226.3) 1028 (1052.6) 9624 (851.9) Serious AE 15 (134.2) 478 (68.1) 92 (94.2) 498 (44.1) Fatal AE 3 (26.8) 11 (1.6) 5 (5.1) 31 (2.7) Treatment-related AE 15 (134.2) 864 (123.1) 152 (155.6) 928 (82.1) Treatment-related serious AE 0 (0) 65 (9.3) 18 (18.4) 59 (5.2) Treatment-related fatal AE 0 (0) 2 (0.3) 0 (0) 3 (0.3) Thrombotic events 1 (8.9) 44 (6.3) 5 (5.1) 52 (4.6) Hemorrhage events 54 (483.2) 1868 (266.1) 233 (238.6) 1591 (140.8) Fatal hemorrhage events 1 (3.7) 0 (0) 0 (0) 5 (0.8) Bone marrow reticulin /collagen events* 1 (8.9) 11 (2.0) 0 (0) 7 (0.8) Hematologic malignancies/MDS 0 (0) 6 (0.9) 4 (4.1) 8 (0.7) Any malignancies 0 (0) 24 (3.4) 9 (9.2) 43 (3.8) * Bone marrow collagen reported in one romiplostim-treated nonsplenectomized pt. Excludes study NCT00907478 as bone marrow evaluations were collected differently than in other studies; in the romiplostim arms the N/pt-yrs were 331/560.6 for splenectomised and 546/866.7 for nonsplenectomised pts. Disclosures Rodeghiero: GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Suppremol: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Steurer:Amgen: Honoraria. Godeau:Amgen: Consultancy. Carpenter:Amgen: Employment, Equity Ownership. Kreuzbauer:Amgen: Employment, Equity Ownership.
31
Lanzillotta, M., E. Della Torre, C. Campochiaro, G. Mancuso, and L. Dagna. "SAT0528 CLINICAL PHENOTYPES OF IGG4-RELATED DISEASE REFLECT DIFFERENCES IN EPIDEMIOLOGICAL FEATURES, SEROLOGICAL FINDINGS, AND PROGNOSTIC OUTCOMES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1221.1–1222. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1438.
Повний текст джерелаАнотація:
Background:Four clinical phenotypes of IgG4-Related Disease (IgG4-RD) have been recently identified by Latent Class Analysis (LCA) - Pancreato/biliary (Group 1); Retroperitoneum/Aortitis (Group 2); Head-and-neck limited (Group 3); Mickulicz/Systemic (Group 4) - but the relevance of this classification for patient management remains unknown (1,2).Objectives:We aimed to assess whether clinical judgment can replicate LCA classification and to evaluate potential differences in epidemiological features, serological findings, and disease outcomes between disease phenotypes.Methods:The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA derived phenotypes based on clinical judgment. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD Responder Index (RI); history of atopy, diabetes, osteoporosis, relapses, and tumors; cumulative dose of glucocorticoids and use of rituximab.Results:Clinical judgment recapitulated LCA classification with strong agreement between IgG4-RD experts (κ= 0.841, p < 0.0005). Group 1 showed the highest levels of serum IgG4 and IgE. Group 2 and 4 had the lowest and highest IgG4-RD RI, respectively (Table 1). Increased cumulative doses of glucocorticoids and higher relapse rate were observed in Group 3 (Fig 1). A higher incidence of diabetes mellitus was observed in Group 1 and 4.Table 1Clinical and serological characteristics of patients cohort.Group 1(59 pts - 45%)Group 2(29 pts - 22%)Group 3(25 pts - 19%)Group 4(18 pts - 14%)P valueFemale n° (%)12 (20%)8 (28%)11 (44%)5 (28%)0.18Age67 (61-73)61 (56-70)52 (40-62)57 (51-62)<0.0001Serum IgG4 (mg/dL)331 (184-575)155 (49-258)150 (80-255)282 (166-460)0.0009IgG4-RD RI9 (6-9)6 (6-9)9 (6-12)9 (6-13)0.004Definite diagnosis n° (%)20 (34%)18 (62%)20 (80%)10 (55%)0.0008Probable diagnosis n° (%)1 (0.59%)0 (0%)1 (0.19%)1 (0.14%)0.6Possible diagnosis n° (%)38 (64%)10 (34%)4 (16%)7 (39)0.0003Emergency Department n° (%)37 (63%)14 (48%)7 (28%)10 (55%)0.03History of atopy n° (%)7 (12%)4 (14%)7 (28%)6 (23%)0.09ESR (mm/h)20 (8-39)40 (14-59)38 (14-54)12 (8-21)0.04CRP (mg/L)5 (2-8)10 (3-52)8 (3-28)3 (2-6)0.03Eosinophils (cell/mm3)200 (200-500)200 (100-275)300 (200-475)200 (100-500)0.3IgE (U/mL)283 (97-723)69 (28-264)120 (41-412)219 (54-657)0.02Plasmablast (cell/mL)1765 (627-4000)1890 (1020- 4000)2000 (370- 4780)2690 (140-5130)0.99Diagnostic delay (months)4 (2-9)7 (4-12)10 (3-18)11 (2-38)0.04Starting prednisone dose(mg, range)60 (37-70)50 (40-75)65 (40-90)40 (30-70)0.8Diabetes at disease onset10 (17%)1 (3%)2 (8%)2 (11%)0.09Figure 1.Relapse free survival of the four different IgG4-RD phenotypes.Conclusion:Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.References:[1]Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS. 2018;126:459-476.[2]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78:406-412.Disclosure of Interests:Marco Lanzillotta: None declared, Emanuel Della Torre: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gaia Mancuso: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.
32
Shipley, W. U., D. Hunt, H. R. Lukka, P. Major, N. M. Heney, D. Grignon, M. Patel, J. Bahary, C. A. Lawton, and H. M. Sandler. "Initial report of RTOG 9601, a phase III trial in prostate cancer: Effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3,N0 disease and elevated PSA levels." Journal of Clinical Oncology 29, no. 7_suppl (March 1, 2011): 1. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.1.
Повний текст джерелаАнотація:
1 Background: To test if long term AAT when combined with RT in these patients (pts) with prostate cancer (PC) will improve cancer control outcomes as well as overall survival (OS). Methods: Post-RP pts with pT3,N0 or with pT2,N0 (and positive margins) who have an elevated PSA were entered on a phase III, double-blinded, placebo-controlled trial of RT alone (64.8 Gy in 1.8 Gy fractions) vs RT + AAT (24 months of bicalutamide, 150mg daily) during and after RT. The primary end point is OS. Results: From 3/98 to 3/03, 771 eligible pts (median age 65) were randomized to RT + AAT (387) or RT alone (383). Pretreatment characteristics were balanced. 672 (87%) had a PSA nadir after RP of < 0.5 ng/mL. 655 (85%) had an entry PSA value of <1.6, 115 (15%) had an entry PSA of 1.6-3.9. Median follow-up was 7.1 years. Actuarial OS at 7 years was 91% for RT + AAT and 86% for RT alone. Too few primary end-point events have occurred to allow a statistical comparison between groups. Freedom from PSA progression (FFP) at 7 years was 57% for RT + AAT and 40% for RT alone (P < 0.0001); for 226 pts with GS < 7 were 63% and 50% (P<0.02), for 411 GS 7 these were 55% and 39% (P<0.0006), and for 134 GS 8-10 were 56% and 26% (P < 0.0008). The 7-yr cumulative incidence of metastatic PC was less in the RT and AAT arm, 7% vs 13% in the RT arm (p<0.041). Late grade 3-4 toxicities were similar in both arms. By category the combined grade 3-4 toxicities for RT + AAT and RT alone were: bladder 6% vs 5% bowel 2% vs 1%, cardiac 3% vs 2%. Gynecomastia (mostly grades 1-2) differed significantly, 89% vs15%. In the RT + AAT arm grade 3 was the highest liver toxicity, which occurred in 3 pts. Conclusions: The addition of 24 months of bicalutamide 150 mg daily during and after RT significantly improved FFP and reduced the incidence of metastatic PC without adding significantly to RT toxicity. The significance of benefit in OS, as well analysis of risk-stratified subsets, wait longer follow-up. No significant financial relationships to disclose.
33
Sasaki, Koji, Nina Shah, Qaiser Bashir, Chitra M. Hosing, Uday R. Popat, Yago Nieto, Simrit Parmar, et al. "Outcome of Patients with Light Chain Multiple Myeloma Compared to IgG/IgA Myeloma after Autologous Stem Cell Transplant." Blood 126, no. 23 (December 3, 2015): 3194. http://dx.doi.org/10.1182/blood.v126.23.3194.3194.
Повний текст джерелаАнотація:
Abstract Introduction: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for younger patients with newly diagnosed multiple myeloma (MM). In approximately 15% of MM patients the monoclonal (M) spike consists of k or l light chains only as opposed to heavy + light chains. It remains unclear whether light chain (LC) MM has a different prognosis compared to other monoclonal protein subtypes after an auto-HCT. Methods: We retrospectively analyzed 1067 patients with MM who underwent auto-HCT between January 1, 2004 and January 1, 2011 at our institution. We evaluated the outcome of newly diagnosed patients with LCMM and compared it to patients with IgG or IgA MM, who underwent an auto-HCT after induction therapy. Primary endpoints were complete remission (CR), progression-free survival (PFS) and overall survival (OS) from the date of auto-HCT. Kaplan-Meier analysis with the log-rank test was performed for univariate comparison of survival. Cox proportional hazards regression method was used for univariate and multivariate analyses. Results: Of 1067 patients who underwent auto-SCT during the period, 223 underwent auto-SCT after relapse, and were excluded. From the remaining 844 who underwent auto-SCT in first remission, we excluded 102 patients (AL amyloidosis 60, POEMS and other plasma cell disorders 10, non-secretory MM 15, IgD 10, IgM 6 and IgE 1) from the analysis. The remaining 742 patients were divided as follows: IgA, 162 patients (22%); IgG, 444 (60%) and LC, 136 (18%). Baseline patient characteristics are described in Table 1. Patients with LCMM were younger and had a higher CR rate to induction. Median follow-up for the entire cohort after auto-HCT was 38 months (range, 0.2-87.0). Post auto-HCT, 28% with IgG/IgA MM and 38% with LCMM achieved a CR (p=0.015). Median PFS was 26.0 months and 27.7 months in IgG/IgA MM and LCMM groups, respectively (p= 0.742). Median OS was not reached and 71.1 months in IgG/IgA MM and LCMM groups, respectively (p= 0.18, Figure 1). Multivariate Cox regression analysis for PFS identified <PR after auto-SCT, non-diploid karyotype, and induction chemotherapy without thalidomide or bortezomib as adverse prognostic factors. Multivariate Cox regression analysis for OS identified presence of hypodiploidy or monosomy 13/del13, higher lactate dehydrogenase pre-transplant, lower hemoglobin pre-transplant, and <PR after auto-HCT as adverse prognostic factors. M protein subtype did not affect PFS (hazard ratio [HR], 1.040; 95% confidence interval [CI], 0.825-1.311; p=0.742) or OS (HR, 1.313; 95% CI, 0.874-1.971; p=0.190). Conclusions: Patients with LCMM have a higher CR rate after auto-HCT, but their PFS and OS were similar to patients with IgG/IgA MM. Table 1. Patient Characteristics Variables, No. (%)/median (range) IgG/IgA myelomaN= 606 Light chain myelomaN= 136 P Median age at transplant, (y) 59 (31-80) 56 (32-78) .004 Age >65 years 138 (23) 23 (17) .134 Male 357 (59) 74 (54) .337 Ethnicity .731 Caucasian 399 (66) 94 (69) African American 99 (16) 22 (16) Mixed 87 (14) 18 (13) Asian 16 (3) 2 (2) Cytogenetic abnormalities at diagnosis by conventional cytogenetics Diploid 180 (30) 36 (27) .159 Hyperdiploid 93 (15) 9 (7) .008 Hypodiploid 27 (5) 11 (8) .082 t(11;14) 4 (1) 3 (2) .092 Monosomy 13 / del 13 44 (7) 9 (7) .789 Other high-risk abnormalities 2 (0) 1 (1) .456 Induction chemotherapy Bortezomib or IMiD-based 507 (84) 123 (90) .046 Pre-transplant evaluation Bone marrow plasma cell, (%) 2 (0-71) 2 (0-50) .136 Bone marrow plasma cell >10% 90 (15) 18 (13) .735 Hemoglobin, (g/dL) 11.3 (4.4-16.0) 10.8 (6.8-15.3) .025 Lactate dehydrogenase, (IL/L) 526 (221-5062) 526 (239-2748) .522 Calcium, (mg/dL) 9.0 (7.6-10.4) 9.0 (7.5-11.0) .055 Creatinine, (mg/dL) 0.9 (0.4-12.5) 0.9 (0.5-9.8) .017 Beta-2 microglobulin (mg/dL) 2.4 (1.1-40.0) 2.8 (1.2-33.8) .001 Time from diagnosis to auto-HCT (month) 8.0 (1.9-174.4) 6.8 (2.4-44.6) .001 Pre-transplant disease status .004 ≥ CR 24 (4) 15 (11) VGPR/PR 545 (90) 109 (80) SD/PD 37 (6) 12 (9) Conditioning regimen .008 Melphalan alone 508 (84) 126 (93) Melphalan-based regimen 98 (16) 10 (7) Final response after transplant .080 ≥ CR 168 (28) 52 (38) VGPR/PR 353 (58) 70 (52) SD/PD 81 (13) 14 (10) Figure 1. a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma Figure 1. a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma Disclosures Shah: Celgene: Consultancy, Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding.
34
Mirlashari, Mohammad Reza, Ingrid Randen та Jens Kjeldsen-Kragh. "Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Induces Apoptosis In Leukemic Cells through Mitochondria-Dependent Pathway". Blood 116, № 21 (19 листопада 2010): 2889. http://dx.doi.org/10.1182/blood.v116.21.2889.2889.
Повний текст джерелаАнотація:
Abstract Abstract 2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to the contradictory roles of GSK-3β as a mediator of both cell survival and apoptosis, we have examined the role of GSK-3β for proliferation and apoptosis in leukemic cell lines KG1a, K562 and CMK. GSK-3β was selectively inhibited by the small-molecule SB-415286. Treatment of leukemia cells with SB-415286 (40 μM) for 72 hr approximately halved cell growth in all three cell lines. SB-415286 also showed a concentration-dependent stabilization of intracellular β-catenin: In KG1a cells the mean fluorescence intensity (MFI) [± 95% CI] was 3.1 [± 1.7] in untreated cells vs. 423 [± 24] in treated cell. The figures for the K562 and CMK cell lines were: 2.8 [± 1.6] vs. 353.2 [± 11.1], and 6.8 [± 4.0] vs. 320.2 [± 23.7], respectively. Cell cycle analysis was carried out to examine if the growth inhibition was caused by arrest in cell cycle and/or induction of apoptosis. We found that SB-415286 caused cell cycle arrest in the G2/M phase and accumulation of events corresponding to the subG1 phase, indicative of DNA fragmentation. The subG1 population was 45%, 34% and 17% in KG1a, K562 and CMK cells, respectively. To confirm that the increase of the subG1 fraction represented an apoptotic effect of the GSK-3β inhibition, we analyzed phosphatidylserine (PS) externalization and plasma membrane integrity. We found that SB-415286 caused a considerable increase of the proportion of early apoptotic cells, i.e. cells that were annexin V-positive and 7-AAD-negative: Mean [± 95% CI] in KG1a cells increased from 6.2% [± 1.2%] in untreated cells to 38% [± 3.1%] in treated cells. The figures for the K562 and CMK cell lines were: 3.0% [± 1.2%] vs. 29% [± 3.3%], and 3.9% [± 1.0%] vs. 16.0% [± 1.1%], respectively. Apoptosis signaling can be initiated by extracellular (death receptor) and/or intracellular (mitochondrial) signals. Flow cytometric analysis of cells stained by a dual-fluorescent mitochondrial dye JC-1 showed that 5–11% of untreated leukemic cells had low mitochondrial membrane potential. After 72 hr exposure to SB-415286 the mean [±95% CI] loss of the mitochondrial potential was found in 23% [± 2.0%], 33% [± 3.5%] and 42% [± 3.8%], in CMK, K562 and KG1a cells, respectively. Since drug treatment in some cell types may result in activation of both the intrinsic or extrinsic cell-death pathway in a parallel manner, we investigated if the external pathway is involved in SB-415286-induced apoptosis. For this purpose we assessed caspase-8 activation by flow cytometry. After 72 hr of treatment of CMK, K562 and KG1a cells the caspase-8 activities compared, to untreated cells, had increased 3.7-fold, 3.9-fold, and 4.4-fold, respectively. In some cell types, the extrinsic cell-death pathway leads to the cleavage of Bid (pro-apoptotic member of the Bcl-2 family) by caspase-8, generating a truncated version of the protein (tBid) which in turn activates the mitochondrial apoptotic pathway. Therefore, we determined whether depolarization of the mitochondrial membrane in the leukemic cell lines was an effect of activated caspase-8 or a direct effect of SB-415286. For this purpose Z-IETD-FMK (25 μM), a specific inhibitor of caspase-8, was applied to the cells for 2 hr. We found that inhibition of caspase-8 did not prevent SB-415286-induced apoptosis assessed by PS externalization. This indicates that activation of caspase-8 is part of the intrinsic apoptotic pathway and occurs downstream of mitochondria membrane potential depolarization mediated by other caspases. Taken together, our observations suggest that inhibition of GSK-3β induces apoptosis of leukemic cells by depolarizing the mitochondria membrane. Thus, inhibition of GSK-3β could be an attractive target for treatment of leukemia. Disclosures: No relevant conflicts of interest to declare.
35
Friedrichs, Birte, Andre Tichelli, Andrea Bacigalupo, Nigel H. Russell, Tapani Ruutu, Meral Beksac, Gerard Socie, and Norbert Schmitz. "Long Term Outcome and Late Effects in Patients Transplanted with Filgrastim-Mobilized Blood or Bone Marrow Treated in a Randomized Trial. A Study from the EBMT Late Effects Working Party." Blood 112, no. 11 (November 16, 2008): 451. http://dx.doi.org/10.1182/blood.v112.11.451.451.
Повний текст джерелаАнотація:
Abstract In 2002, the EBMT reported on the largest prospective randomized study comparing filgrastim-mobilized peripheral blood progenitor cell (PBPC) to bone marrow (BM) transplantation (Schmitz et al. Blood 2002). Patient accrual took place between 02/95 and 09/99 and included 329 patients transplanted from HLA-identical sibling donors mostly for early leukaemia (ALL, AML, MDS, CML). Here we report long-term follow-up data collected at a median of 9.1 years (BM 9.2 yrs; PBPC 8.9 yrs) after transplantation. Questionnaires on long-term events of allogeneic transplantation were sent out to the treating centers of all 202 patients surviving at 3 years post-transplant. Follow-up data were available for 162 patients (80.2%; BM n = 86; PBPC n = 76) from 38 of 42 centers (90.4%). The 8-year overall survival (OS) was 46.0 % for PBPC recipients versus 54.1 % for BM recipients (p = 0.23). Leukemia-free survival (LFS) was 43.7% for PBPC recipients versus 46.2% for BM recipients (p = 0.66). Late deaths (> 3 years) occurred in 22 cases (9 BM, 13 PBPC); 8 patients died due to relapse (4 BM, 4 PBPC). While relapse remains the most frequent cause of late deaths, non-relapse mortality included secondary malignancy (n = 1), GvHD (n = 4), brain hemorrhage (n = 2), other/unknown (n = 7), and did not show differences between BM and PBPC. Late relapses (>3 years) occurred in 11 patients (9 BM; 2 PBPC); the cumulative incidence of late relapse with death as competing risk was 18.4% for BM and 6.8% for PBPC (p = 0.056). While for AML and ALL no differences in relapse rate (RR) were found between the two treatment groups, CML patients showed a significantly lower RR after transplantation with PBPC (BM 19.4% PBPC 6.8%; p = 0.036). Fourteen cases of secondary malignancies occurred (5 BM; 9 PBPC) (1 lymphoma, 1 lung cancer, 1 prostate cancer, 2 thyroid cancer, 1 squamous cell cancer, 3 basalioma, 1 histiocytofibroma, 1 ependymoma, 1 tongue carcinoma, 1 breast cancer, 1 cervix carcinoma). For 3-year-survivors, the cumulative incidence of secondary malignancy with death as competing risk was 7.2% for BM and 16.1% in the PBPC group (p = 0.16). Significantly more patients transplanted with PBPC than with BM have developed chronic GvHD (72.6% vs 54.1%, p=0.013) with also a higher cumulative incidence of extensive disease (56.3% vs. 30.4%; p=0.002). Five years after transplantation, 29.4% (20/68) of patients transplanted with PBPC were reported to be still on immunosuppressive drugs, compared to 10.6% (10/75) of the BM group (p=0.004). Nonetheless, there was no difference in mean performance status (mean ECOG = 0.5; range 0–3). Sixty-nine percent of the 3-year survivors have returned to work with no difference between treatment groups. Among 3-year survivors, overall incidence of bronchiolitis obliterans and cataract was 9.8% each, with no differences between the recipients of BM (10.8% and 9.8%) and PBPC (8.7% and 10%). Long-term hematopoietic function was similar in both treatment groups with median concentrations of hemoglobin of 141g/L (range 10.1–17.4) vs. 139g/L (range 10.0–16.6) and median platelet counts of 225G/L (range 120–554) vs. 251G/L (range 109–425) for BM and PBPC recipients, respectively. In conclusion, OS and LFS remain similar between BM and PBPC transplanted recipients with an increasing trend to better OS for patients transplanted with BM. The higher incidence of cGvHD in the PBPC group resulted in longer times of immunosuppression in a higher number of patients. Lower relapse rates in CML for patients transplanted with PBPC might be the consequence of a more intense GvL effect. However, overall these differences did not affect survival outcomes, general health status and the occurrence of late events in recipients treated with BM and PBPC.
36
Jeria Navarro, S., T. Franco, L. Alserawan, D. Lobo Prat, A. García-Guillén, L. Sainz Comas, H. Park, et al. "POS0827 HEPATOTROPIC VIRUSES WITH HIGHER RHEUMATOID FACTOR, BUT NOT RHEUMATIC DISEASES LINK TO PREVALENT CRYOGLOBULINEMIA. CORRELATION OF CLINICAL AND SEROLOGICAL MARKERS WITH ETIOLOGICAL CAUSES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 666.2–667. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1758.
Повний текст джерелаАнотація:
Background:Cryoglobulinemia (CG) is a rare phenomenon, which is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate in vitro at less than 37°C and dissolve when the temperature rises again. Is related to hematological disorders, infections and autoimmunes diseases.Objectives:To describe the differential clinical features, serological and demographics in a cohort of patients diagnosed with CG.Methods:We describe a retrospective cohort of 252 cryoglobulin (Cg) positive samples, obtained from a database from the immunology laboratory of a tertiary hospital (November 2018-November 2019). We obtained 182 patients with CG, classified according to their etiology into 4 groups: 1)Rheumatic diseases (RD) that includes rheumatoid arthritis, Systemic lupus erythematosus, Sjögren´s syndrome and Systemic scleroderma, 2)Hepatotropic viruses (HV) with patients diagnosed with Hepatitis C virus, B virus and both, 3)Hematological diseases (HD) and 4)Essential cryoglobulinemia (CGE). Demographic variables, clinical and serological data were collected. A comparative analysis was performed with the Mann-Whitney U test and the multivariate Kruskal-Wallis test, nonparametric variables were compared using a Wilcoxon test. Ten patients, with more than one disease from 4 groups, were excluded from the study.Results:Out of 182 reviewed patients, 172 were included in the study. Mean age at diagnosis was 59.7(±14.0). Demographic, clinical and laboratory characteristics are described in table 1. Mixed CG was the predominant subtype, in 116 (67.4%) patients. The most prevalent CG-associated diseases were HV infection with 91(53%) patients. CGE mostly presented with cutaneous manifestations (p=0.0001), particularly purpura. In RD group the presence of Raynaud and non-erosive arthritis (p=0.0001) was relevant. Laboratory findings showed that CG titration varies according to the etiology, being HD the one with the highest values with 292.2 (±546.2). There is significant difference in terms of the average of rheumatoid factor (RF) being higher in the group by CGE. On other hand, the group HV presented more consumption of complement, and showed the lowest average p=0.0001, without more severe clinical manifestations.RD (n=47)HV (n=91)HD (n=17)CGE (n=17)Gender,n(%) F42 (89.4)57 (62.6)7 (41.2)11 (64.7)Age at dg, years, (± SD)60.6 (±14)59.6 (±13.1)61.1(±16.6)56.3(±20.8)p=0.8CLINICAL CHARACTERISTICSSkin n (%)18 (38.3)10 (11.0)2 (11.8)9 (52.9)p<0.001Raynaud n (%)14 (29.8)1 (5.9)3 (17.6)p<0.001Purpura n (%)6 (12.8)9 (9.9)2 (11.8)6 (35.3)p=0.04Acrocyanosis n (%)6 (12.8)1 (5.9)p=0.0033Ulcers n (%)3 (6.4)2 (2.2) -2 (11.8)p=0.19Peripheric Neuro n (%)10 (21.3)9 (9.9)1 (5.9)4 (23.5)p=0.13N-E arthritis n (%)22 (46.8)8 (8.8)1 (5.9)4 (23.5)p<0.001GMN n (%)5 (10.6)3 (3.3)1 (5.9)3 (17.6)p=0.11LABORATORYCg (mg/dL) x (± SD)26.7 (±63.2)65.8 (±256.5)292.4 (±546.2)47.59 (±79.1)p<0.001Isotype IgG, n (%)G+M 26 (55.3)G+M 72 (79.1)M 8 (47.1)G+M 12 (70.6)β2M (≥1.8 mg/L), n (%)7/40 (17.5%)1/5 (20.0%)3/12 (25.0%)-p= 0.44RCP (mg/L) p 5010.3 (±26.2)3.9 (±3.0)13.4 (±18.3)8.5 (±12.0)p= 0.47ESR (mm/h) p5040.0 (±28.5)20.3 (±20.2)35.4 (±35.1)24.5 (±25.0)p= 0.0003RF + (>20UI/mL), n (%)19/46 (41.3)44/86 (51.2)5/11 (45.5)7/17 (41.2)p= 0.09p5090.6 (±175.9)161.0 (±219.5)94.8 (±135.6)284.5 (±619.3)p<0.001C3 (<85mg/dL), n %)20 (42.6)47 (51.6)3 (17.6)3 (17.6)p= 0.13x (± SD)90.1 (±28.6)68.5 (±10.8)99.1 (±29.0)114.8 (±12.7)p<0.001C4 (<12mg/dL), n (%)17 (36.2)36 (39.6) -3 (17.6)p= 0.02x (± SD)15.6 (±9.0)7.6 (±3.5)20.4 (±7.4)21.1 (±9.5)p<0.001Conclusion:In our cohort, not all patients with CG presented clinical manifestations being those associated with CGE and RD those with the highest skin and joint expression. The most prevalent association of CG continues to be the HV and we confirmed the characteristic decrease in C3 and C4 complement levels, together with the positivity for RF.Disclosure of Interests:None declared
37
Santos, Cedric Emmanuel Dos, Tinisha McDonald, Liang Li, Allen Lin, Ya-Huei Kuo, and Ravi Bhatia. "SFK Inhibition with Dasatinib Results In Selective Targeting of Primitive Human Acute Myeloid Leukemia Stem and Progenitor Cells." Blood 116, no. 21 (November 19, 2010): 1053. http://dx.doi.org/10.1182/blood.v116.21.1053.1053.
Повний текст джерелаАнотація:
Abstract Abstract 1053 The Src family tyrosine kinases (SFKs) are abnormally activated in AML compared to normal CD34+ hematopoietic progenitors. Studies using pharmacological and siRNA approaches indicate an important role for the SFK Lyn in AML progenitor cell growth and survival (Dos Santos et al., 2008). However the role of SFKs in AML leukemic stem cell (LSC) growth and survival is not clear. SFK activity in Lin- CD34+ CD38- primitive stem/progenitor cells, Lin- CD34+ CD38+ committed progenitors, and Lin-CD34- cells from primary human AML (n=14) and cord blood (CB) (n=6) samples was measured by analyzing SFK phosphorylation using flow cytometry. We observed significant increase of SFK phosphorylation in AML compared to CB Lin- CD34+CD38- cells (3.8±1.9 versus 1.9±0.7, p=0.006), Lin- CD34+ CD38+ (3.9±1.7 versus 1.9±0.6, p=0.013) and Lin- CD34- cells (3.4±1.8 versus 1.1±0.5, p=0.0005). Dasatinib, a potent SFK and ABL kinase inhibitor, is approved for clinical use in chronic myeloid leukemia. We evaluated the effect of SFK inhibition using Dasatinib on the growth and viability of AML stem and progenitor cells. Dasatinib exposure resulted in dose-dependent inhibition of SFK phosphorylation in each subpopulation (in CD34+ CD38-, 3.0 for the control versus 1.9 with 100nM and 1.6 with 500nM, in CD34+ CD38+, 2.8 for the control versus 1.9 with 100nM and 1.6 with 500nM) after 30 minutes of drug treatment). The addition of Dasatinib (10-500nM) to methylcellulose progenitor assays resulted in dose-dependent inhibition of AML colony forming cell (CFC) growth (83.9±16.1% inhibition with 500nM, and 48.1±6.8% inhibition with 10nM Dasatinib, n=8), to a greater extent than CB CFC to (CFU-GM inhibition 62.6±1.5% with 500nM, and 1.1±16.3% with 10nM Dasatinib, n=4). Short-term exposure to Dasatinib (10-500nM) for 48 hours also resulted in significantly greater inhibition of AML CFC (73.6±13% with 500nM, and 41.7±10.8% with 10nM Dasatinib, n=8) compared to CB CFC (CFU-GM inhibition 23±9.1% with 500nM, and 1.3±11.3% with 10nM Dasatinib, n=4). Importantly Dasatinib treatment (200nM) also resulted in reduction of AML stem/primitive progenitor growth in long term culture-initiating cells (LTC-IC) assays (56±23, 8 % inhibition, p=0.003, n=4), suggesting that SFK inhibition may inhibit AML stem cell maintenance. The effect of Dasatinib on apoptosis was evaluated by labeling cells with Annexin V and DAPI. Treatment with Dasatinib resulted in significant increase in apoptosis of Lin- AML cells (41.5% ±10.7 of apoptosis with 200nM Dasatinib versus 25%±10.8 for the control, p=0,004, n=5) We studied the effects of Dasatinib on differentiation of Lin- CB (n=3) and AML cells (N=5) cultured with SCF, IL-3, GM-CSF, G-CSF and EPO. In normal CD34+, Dasatinib (100 nM) treatment resulted in increased CD33+ and CD14+ cells and reduced CD34+, CD11b+, CD15+, GPA+ and CD71+ cell numbers, indicating that SFK increased monocytic but reduced granulocytic and erythroid differentiation. Treatment of AML cells with Dasatinib resulted in markedly reduced numbers of CD34+, CD33+ and CD71+ cells, but increased numbers of CD11b cells, in 3 of 5 samples, indicating a trend towards increased granulocytic differentiation in contrast to normal progenitors. Our results indicate that SFK activity is increased in primary human AML stem and progenitor cells and suggest that SFK blockade with Dasatinib may reduce maintenance of AML LSC/ primitive progenitors, through inhibition of progenitor proliferation, induction of apoptosis and enhancement of differentiation. These results support further evaluation of SFK blockade with Dasatinib for targeting of AML stem and progenitor cells in preclinical and clinical studies. Disclosures: Bhatia: Novartis: Consultancy, Honoraria.
38
Pandya, Bharati, Tanweerul Huda, Dilip Gupta, Bhupendra Mehra, and Ravinder Narang. "Abdominal Wall Hernias: An Epidemiological Profile and Surgical Experience from a Rural Medical College in Central India." Surgery Journal 07, no. 01 (January 2021): e41-e46. http://dx.doi.org/10.1055/s-0040-1722744.
Повний текст джерелаАнотація:
Abstract Background Abdominal wall hernia is a common surgical entity worldwide with groin hernias having the most common presentation among them. They are a cause of morbidity and mortality if not addressed in time. A variety of surgical methods are available for the repair of hernias. The tension-free repair using synthetic mesh has the least recurrence and is the most accepted. Aim To describe the surgical burden and clinical profile of abdominal wall hernias as well as experiences in their management in a rural setup. Methods This was a retrospective observational study of all the cases of abdominal wall hernias presenting to various surgical divisions of Mahatma Gandhi Institute of Medical Sciences, Sevagram, during a two-year period from December 2011 to November 2013. Relevant details were collected from the hospital information statistics and patient file records and analysis of obtained data was done. Result A total of 910 out of 90,056 surgical outpatients (10.10%) seen during this period had abdominal wall hernias; 816 (89.67%) got operated. A total of 163 (20%) of 816 were operated in an emergency. Groin hernias were the most common 653 (80%), followed by incisional 82 (10%), umbilical and paraumbilical 41 (5%), epigastric 33 (4%), and rarer hernias in 8 (1%). Of 816 operations, 24 (2.9%) had recurrent hernias and 83 (10.17%) were pediatric patients. Male to female ratio was 9:1 in adults and 4:1 in children. The median age among adults was 49 years (range: 14–95 years), and among the pediatric age group, it was 7 years (range: 3 months–14 years). The majority of the adult patients were from a low-income group and presented more than 2 years after symptoms appeared. Comorbid conditions encountered were hypertension in 212 (26%), diabetes in 155 (19%), chronic airway disorders in 449 (55%), cardiac problems in 163 (20%), obesity in 10 (1.2%), and chronic renal failure and liver disorder in 82 (1%). Predisposing factors in the majority of the patients were chronic cough 449 (55%), prostatic problems in 187 (23%), chronic constipation in 163 (20%), previous surgeries in 82 (10%), obesity in 10 (1.2%), and ascites in 9 (0.1%). Hernia surgery was performed laparoscopically in 51 (6.25%) patients. Simultaneous other surgeries were performed in 130 (16%) patients. Mortality occurred in 2 (0.24%) patients operated in emergency, and chief morbidity was due to wound infection in 25 (3%) and chronic pain in 30 (3.9%) patients. Conclusion Abdominal wall hernias are common clinical entities. Although the pattern of presentation and management is similar, the challenges faced in a rural setup are due to ignorance, social inhibitions, and financial restraints, leading to delayed presentations which increase their morbidity and mortality. Health programs and surveys to increase awareness in rural areas as well as cutting down on expenses could help these patients.
39
Thanarajasingam, Gita, James M. Foran, Vivek Roy, Lisa Sproat, William J. Hogan, Mark R. Litzow, Aref Al-Kali, Naseema Gangat, and Mrinal M. Patnaik. "Hematopoietic Stem Cell Transplantation As a Successful Salvage Strategy for Relapsed Acute Promyelocytic Leukemia (APL): A Mayo Clinic Series." Blood 124, no. 21 (December 6, 2014): 3995. http://dx.doi.org/10.1182/blood.v124.21.3995.3995.
Повний текст джерелаАнотація:
Abstract Background: Relapse after ATRA-based induction therapy is relatively uncommon in patients with acute promyelocytic leukemia (APL). Long term follow up studies have estimated a 15-25% relapse rate. Autologous and allogeneic hematopoietic stem cell transplantation (HCT) has been used as an effective salvage strategy. We present a single institution study of the outcomes of patients with relapsed APL that underwent HCT. Methods: After due IRB approval, the Mayo Clinic Transplant Database was retrospectively reviewed to identify all patients across three Mayo Clinic sites with relapsed APL that underwent HCT from 1995-2013. Data was abstracted at diagnosis and at relapse. The aims of this study were to report the descriptive characteristics of patients, with a focus on HCT outcomes. Results: Baseline Patient Characteristics A total of 15 patients (9 (60%) males) with relapsed APL that underwent HCT were identified. Median age was 36 years (range: 19-63) and median follow up from diagnosis was 8.8 years (range: 1.7-17). 2 (13%) deaths (1 from relapse) were recorded. 14 (93%) received ATRA and anthracycline-based induction therapy and 1 received anthracycline-based induction without ATRA. All relapsed patients achieved a complete remission (CR) after induction. Median time to relapse was 1.6 years (range: 0.6-3.9). 10 (67%) patients had a medullary relapse (hematologic-7(70%), cytogenetic -2 (20%) and molecular-1(10%)), 3 (20%) had additional extramedullary (EM) disease (CNS-2, myeloid sarcoma-1), while 2 (13%) presented with EM disease only (CNS-2). Salvage regimens included ATRA in 5 (33%) patients and arsenic trioxide (ATO) in 8 (53%) patients. 12 (80%) patients were transplanted in CR2 and 1 in CR3 (7%), while 2 (13%) had persistent disease (PD) at time of HCT. Allogeneic HCT 4 (27%) patients with a median age of 37 years (range: 33-49) underwent allogeneic HCT. 2 (50%) patients received myeloablative (MA) conditioning and 2 received reduced-intensity conditioning (RIC). 2 patients who underwent MA HCT had PD at time of transplant, while 1 patient in CR3 received a RIC. 2 (50%) patients developed acute GVHD while 2 (50%) had extensive stage chronic GVHD. At a median follow up of 2.6 years (range: 0.3-10.9), 3 (75%) patients remain alive and disease-free. 1 patient died of infectious complications within 100 days of transplant. Autologous Transplantation 11 (73%) patients with a median age of 40 years (range: 23-68) underwent autologous HCT with MA conditioning. 7 (64%) patients were in molecular remission at time of HCT, 3 (27%) patients transplanted before 2004 were in cytogenetic remission and information about type of remission was unavailable in 1 patient. At a median follow up of 6.8 years (range: 0.5-16) since HCT, 1 (9%) patient had a documented relapse at 175 days after HCT and died of disease-related complications. 10 (91%) are alive and in remission. Conclusions: Our single-institution study reaffirms the efficacy of HCT for APL patients with medullary and EM relapse. Autologous HCT has excellent long-term results in selected patients in CR2. Allogeneic HCT was mainly reserved for patients with high risk disease (CR3) and persistent disease at time of HCT. Table 1: Baseline Patient Characteristics N (%) Number of patients 15 Follow up (years) (median, range) 8.8 (1.7-17) Age at diagnosis (years) (median, range) 36 (19-53) Gender Male 9 (60%) Female 6 (40%) Sanz risk score High 4 (29%) Intermediate 8 (57%) Low 2 (14%) Induction Regimen ATRA + anthracycline 14 (93%) Anthracycline-based 1 (7%) Response to induction therapy CR 15 (100%) Time from diagnosis to relapse (years) (median, range) 1.6 (0.6 - 3.9) Type of relapse Hematologic 7 (47%) Cytogenetic 2 (13%) Molecular 1 (7%) Hematologic and EM 3 (20%) CNS only 2 (13%) Salvage regimen ATRA-based 5 (33%) ATO-based 8 (53%) Chemotherapy only 2 (13%) Table 2: Outcomes at HCT N (%) Age at HCT (years) (median, range) 38 (23-68) Disease status at HCT CR2 12 (80%) CR3 1 (7%) PD 2 (13%) Type of HCT Allogeneic 4 (27%) Autologous 11 (73%) Conditioning regimen Myeloablative 13 (87%) Non-myeloablative 2 (13%) Follow up since HCT (years) (median, range) 4.5 (0.3 - 16.3) Disease status at last follow up CR 13 (86%) Relapsed disease 1 (7%) Unable to assess 1 (7%) Alive at last follow up 13 (87%) Disclosures No relevant conflicts of interest to declare.
40
Viscoli, Catherine M., Lawrence M. Brass, Walter N. Kernan, Philip M. Sarrel, and Ralph Horwitz. "ESTROGEN AFTER ISCHEMIC STROKE: Effect of estrogen replacement on risk of recurrent stroke and death in the Women’s Estrogen for Stroke Trial (WEST)." Stroke 32, suppl_1 (January 2001): 329. http://dx.doi.org/10.1161/str.32.suppl_1.329.
Повний текст джерелаАнотація:
71 Introduction: Observational research has produced conflicting findings concerning the effect of estrogen replacement therapy (ERT) on reducing risk for vascular events or death in women. To test the effect of ERT in women with established cerebrovascular disease, we designed a randomized trial of estradiol-17β(1 mg/day) vs. placebo. Methods: Participants were identified from 20 hospitals in New England. Eligibility criteria included age over 44, at least 1 year since last menstrual period, and TIA or non-disabling stroke within 90 days of entry. Randomization was stratified by baseline risk group and hospital. Primary trial outcomes were non-fatal stroke and all-cause death. Results: From December 1993-May 1998, 652 women were randomized (332 estradiol, 320 placebo). Index event was TIA in 164 subjects and stroke in 488. Mean age of subjects was 71 years (range 46–91); 84% were white, 13% black, and 4% other. Mean follow-up was 2.7 years (range: 18 days-5.8 years). At 1 year, 76% of subjects assigned to estradiol were on study drug. In the estradiol group, adverse events were diagnosed during follow-up in 8 subjects (1 pulmonary embolus (PE), 1 deep venous thrombosis (DVT), 5 breast cancers, 1 endometrial cancer) compared with 7 events in placebo subjects (2 PE, 1 DVT, and 4 breast cancers). Non-fatal strokes were confirmed in 51 subjects in the estradiol group vs. 52 in placebo subjects (rates at 3 years[R]: 16.8% estradiol vs. 17.4% placebo; logrank p-value[p]=.83). Death occurred in 46 estradiol subjects vs. 38 placebo subjects (R=13.0% vs. 12.6%, p=.89). At 3 years, combined rate of non-fatal stroke or death was 27.6% in the estradiol group vs. 27.7% in placebo [p=.80]. Conclusion: During an average follow-up of 2.7 years, estradiol treatment did not protect against recurrent cerebral ischemia or reduce all-cause mortality in postmenopausal women with pre-existing cerebrovascular disease. No increased risk for adverse events associated with estrogen was observed. This trial adds to the growing body of evidence that fails to confirm a protective role for ERT in populations with known vascular disease.
41
Uldrick, Thomas, Mark N. Polizzotto, Deirdre O'Mahony, Karen Aleman, Kathy Wyvill, Seth Steinberg, Stefania Pittaluga, Richard F. Little, and Robert Yarchoan. "Clinical, Biochemical, and Radiographic Responses to Rituximab Combined with Liposomal Doxorubicin (R-Dox) in HIV-Infected Patients with Severe Kaposi Sarcoma-Associated Herpes Virus (KSHV) – Associated Multicentric Castleman's Disease." Blood 114, no. 22 (November 20, 2009): 1651. http://dx.doi.org/10.1182/blood.v114.22.1651.1651.
Повний текст джерелаАнотація:
Abstract Abstract 1651 Poster Board I-677 Background KSHV-associated multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder characterized by fever, splenomegaly, adenopathy, hypoalbuminemia, hyponatremia, cytopenias, elevated inflammatory markers, and a waxing and waning course. Most MCD arising in HIV-infected patients is KSHV-associated. Historically, prognosis has been poor. There is no standard therapy, although benefit has been reported with cytotoxic chemotherapy, interferon-á, retinoic acid and ganciclovir. Rituximab has reported activity in KSHV-MCD, but may not be sufficient as monotherapy in patients with severe disease, and can be associated with worsening of Kaposi's sarcoma (KS). Within a natural history study of KSHV-MCD, we evaluated the treatment effects of R-Dox on correlates of disease activity in patients with severe MCD or MCD with concurrent KS. Methods Patients with biopsy confirmed MCD that was severe or accompanied by severe KS were treated with liposomal doxorubicin 20mg/m2 plus rituximab 375 mg/m2 every 21 days until substantial clinical improvement or disease progression. Post R-Dox therapy, discussed below, was used to consolidate or maintain responses. Clinical, biochemical and radiographic response were evaluated individually using protocol-defined criteria. Overall complete responses (CR) required normalization of all clinical, laboratory or radiographic abnormalities attributed to MCD lasting at least 3 weeks. Results Twelve patients (1 woman, 11 men) have been treated with R-Dox to date. Patient characteristics: median (med) age 43 (range 34-55); all were on HAART, med CD4 331 cells/μL (21-1598), HIV viral load <50 copies/mL in 10 patients. Med number of prior therapies 2 (0-8); concurrent KS (5); dependent on steroids (3); patients hospitalized during first cycle (6). Med baseline values for biochemical response parameters: C-reactive protein 9.7 mg/dL (0.4-21.0), albumin 2.7 mg/dL (1.5-3.4), sodium 133 mEq/L (126-140), platelets 70 K/uL (10-377), hemoglobin 9.4 g/dL (6.8-12.0). 11 had diffuse adenopathy and all had splenomegaly, med spleen 18.5 cm (12.5-28 cm). Patients received med 4 cycles (3-9) of R-Dox. All patients met criteria for clinical CR after a med 2 cycles (range 1-5). Best biochemical response was CR in 9 (75%) and partial response (PR) in 1 (8%); 2 (17%) had stable biochemical parameters. Best radiographic response was CR in 6 (50%) and PR in 6 (50%) with a med 5 cm (+0.5 cm, -10 cm) decrease in spleen size. Best biochemical response was achieved after med 3 cycles (1-7), and best radiographic response after med 3 cycles (2-5). 2 of 12 had an overall CR at completion of R-Dox. Post R-Dox therapy included: IFNá (8), high-dose AZT + valganciclovir (2), additional liposomal doxorubicin (1). To date, another 6 patients achieved overall CR with additional therapy. Concurrent KS improved in 4 of the 5 patients affected. With a median potential follow-up of 25.5 months (actual follow-up range from 5.5+ to 41+ months), 9 of 12 patients have had no MCD relapse after starting R-Dox, 2 patients had recurrent MCD flares (months 7 and 17) that responded to additional therapy and 1 patient had progressive MCD during cycle 6 associated with worsening KS, and died at month 6 of central pontine myelinolysis. He was found to have primary effusion lymphoma at autopsy. An additional patient died of pneumonia (month 17). Toxicity was minimal. 9 patients had infusion reactions (Gr. 1 = 3, Gr. 2 = 4, Gr. 3 = 2) with the first dose of rituximab. 9/55 cycles were complicated by neutropenia (Gr. 2 = 7, Gr. 3-4 = 2). There were no infectious complications. Conclusions R-dox is highly effective in heavily pretreated patients with severe KSHV-MCD or MCD with concurrent severe KS. Further evaluation of R-Dox in patients with severe KSHV-MCD is ongoing. Disclosures Off Label Use: Rituximab and Liposomal Doxorubicin are being explored in the treatment KSHV-MCD.
42
Ko, Andrew H., Jeeyun Lee, MARIA ALSINA, Jaffer A. Ajani, Yung-Jue Bang, Hyun Cheol Chung, Jill Lacy, et al. "Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 4540. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.4540.
Повний текст джерелаАнотація:
4540 Background: The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to identify early efficacy signals and safety of treatment (tx) combinations across cancers. Within MORPHEUS, atezo (anti–PD-L1) was tested with PEGylated recombinant human hyaluronidase (PEGPH20), an anti–stromal and extracellular matrix modulator, in patients (pts) with metastatic (m) PDAC or advanced/mGC. Methods: In 2 separate randomized trials, eligible pts with 2L mPDAC or mGC received atezo (1200 mg IV q3w) + PEGPH20 (3 µg/kg IV on D1, 8, 15). Control tx for M-PDAC (NCT03193190) was mFOLFOX6 or gemcitabine + nab-paclitaxel. In M-GC (NCT03281369), control tx was ramucirumab + paclitaxel. Primary endpoints were ORR (investigator-assessed RECIST 1.1) and safety. Results: Pts were followed up for ≥ 18 wk in M-PDAC (data cutoff: Aug 5, 2019) and ≥ 24 wk in M-GC (data cutoff, Jul 11, 2019). In M-PDAC, 66 pts received atezo + PEGPH20 and 42 received control in both preliminary and expansion phases. Confirmed ORRs were 6.1% (95% CI: 1.7, 14.8) and 2.4% (95% CI: 0.06, 12.6), respectively. Duration of response ranged from 5.3 to 11.3 mo in tx arm and was 3.9 mo in control. Median PFS was 1.5 mo (95% CI: 1.4, 2.6) and 2.3 mo (95% CI: 1.6, 4.0), respectively. Median OS was 7.1 mo (95% CI: 4.6, 9.5) and 6.8 mo (95% CI: 5.6, 8.3). Updated survival data will be presented. Respectively, 62.2% and 59.5% of pts had Gr 3-4 AEs; Gr 5 AEs were seen in 4.5% and 2.4% of pts; serious AEs (SAEs) occurred in 45.5% and 45.2% of pts; 16.7% and 4.8% of pts had tx-related AEs leading to tx withdrawal. The most common tx-related AEs were myalgia (65.2%) and peripheral edema (28.8%) in the combination arm. In M-GC, 13 pts received atezo + PEGPH20 and 12 received control. Confirmed ORRs were 0% (95% CI: 0, 24.7) and 16.7% (95% CI: 2.1, 48.4), respectively. Gr 3-4 AEs were seen in 30.8% and 75.0% of pts, respectively. No Gr 5 AEs occurred in either arm. SAEs occurred in 7.7% and 50.0% of pts, respectively. Only 1 pt in the control arm had a tx-related AE leading to tx withdrawal. While tumor hyaluronan (HA) appears to be associated with poor prognosis in the M-PDAC control, there was no clear association between HA levels and response to atezo + PEGPH20. PK data will also be presented. Conclusions: Limited efficacy was seen with the chemotherapy-free combination of atezo + PEGPH20 in PDAC. No efficacy was seen in GC. The safety of atezo + PEGPH20 was consistent with each agent’s known safety profile; no new safety signals were identified. Clinical trial information: NCT03193190 .
43
Villalva A., Juan Enrique. "Structural equation models - PLS in engineering sciences: a brief guide for researchers through a case applied to the industry." Athenea 2, no. 4 (June 15, 2021): 5–18. http://dx.doi.org/10.47460/athenea.v2i4.17.
Повний текст джерелаАнотація:
Modeling using structural equations, is a second generation statistical data analysis technique, it has been positioned as the methodological options most used by researchers in various fields of science. The best known method is the covariance-based approach, but it presents some limitations for its application in certain cases. Another alternative method is based on the variance structure, through the analysis of partial least squares, which is an appropriate option when the research involves the use of latent variables (for example, composite indicators) prepared by the researcher, and where it is necessary to explain and predict complex models. This article presents a brief summary of the structural equation modeling technique, with an example on the relationship of constructs, sustainability and competitiveness in iron mining, and is intended to be a brief guide for future researchers in the engineering sciences.
Keywords: Competitiveness, Structural equations, Iron mining, Sustainability.
References
[1]J. Hair, G. Hult, C. Ringle and M. Sarstedt. A Primer on Partial Least Square Structural Equation Modeling (PLS-SEM). California: United States. Sage, 2017.
[2]H. Wold. Model Construction and Evaluation when Theoretical Knowledge Is Scarce: An Example of the Use of Partial Least Squares. Genève. Faculté des Sciences Économiques et Sociales, Université de Genève. 1979.
[3]J. Henseler, G. Hubona & P. Ray. “Using PLS path modeling new technology research: updated guidelines”. Industrial Management & Data Systems, 116(1), 2-20. 2016.
[4]G. Cepeda and Roldán J. “Aplicando en la Práctica la Técnica PLS en la Administración de Empresas”. Congreso de la ACEDE, Murcia, España, 2004.
[5]D. Garson. Partial Least Squares. Regresión and Structural Equation Models. USA. Statistical Associates Publishing: 2016.
[6]D. Barclay, C. Higgins & R. Thompson. “The Partial Least Squares (PLS) Approach to Causal Modeling: Personal Computer Adoption and Use as an Illustration”. Technology Studies. Special Issue on Research Methodology. (2:2), pp. 285-309. 1995.
[7]J. Medina, N. Pedraza & M. Guerrero. “Modelado de Ecuaciones Estructurales. Un Enfoque de Partial Least Square Aplicado en las Ciencias Sociales y Administrativas”. XIV Congreso Internacional de la Academia de Ciencias Administrativas A.C. (ACACIA). EGADE – ITESM. Monterrey, México, 2010.
[8]J. Medina & J. Chaparro. “The Impact of the Human Element in the Information Systems Quality for Decision Making and User Satisfaction”. Journal of Computer Information Systems. (48:2), pp. 44-52. 2008.
[9]D. Leidner, S. Carlsson, J. Elam & M. Corrales. “Mexican and Swedish Managers’ Perceptions of the Impact of EIS on Organizational Intelligence, Decisión Making, and Structure”. Decision Science. (30:3), pp. 633-658. 1999.[10]W. Chin. “The partial least squares approach for structural equation modeling”. Chapter Ten, pp. 295-336 in Modern methods for business research. Edited by Macoulides, G. A., New Jersey: Lawrence Erlbaum Associates, 1998.
[11]M. Höck & C. Ringle M. “Strategic networks in the software industry: An empirical analysis of the value continuum”. IFSAM VIIIth World Congress, Berlin 2006.
[12]J. Henseler, Ch. Ringle & M. Sarstedt. Handbook of partial least squares: Concepts, methods and applications in marketing and related fields. Berlin: Springer, 2012.
[13]S. Daskalakis & J. Mantas. “Evaluating the impact of a service-oriented framework for healthcare interoperability”. Studies in Health Technology and Informatics. pp. 285-290. 2008.
[14]C. Fornell & D. Larcker: “Evaluating Structural Equation Models with Unobservable Variables and Measurement Error”, Journal of Marketing Research, vol. 18, pp. 39-50. Februay 1981.
[15]C. Fornell. A Second Generation of Multivariate Analysis: An Overview. Vol. 1. New York, U.S.A. Praeger Publishers: 1982.
[16]R. Falk and N. Miller. A Primer for Soft Modeling. Ohio: The University of Akron. 1992.
[17]M. Martínez. Aplicación de la técnica PLS-SEM en la gestión del conocimiento: un enfoque técnico práctico.
Revista Iberoamericana para Investigación y el Desarrollo Educativo. Vol. 8, Núm. 16. 2018.
[18]S. Geisser. “A predictive approach to the random effects model”. Biometrika, Vol. 61(1), pp. 101-107. 1974.
[19]J. Cohen. Statistical power analysis for the behavioral sciences. Mahwah, NJ: Lawrence Erlbaum, 1988.
[20]GRI (2013). G4 Sustainability Reporting Guidelines. Global Reporting Initiative. Available: www.globalreporting.org
44
van Leeuwen, F. E., A. M. Stiggelbout, A. W. van den Belt-Dusebout, R. Noyon, M. R. Eliel, E. H. van Kerkhoff, J. F. Delemarre, and R. Somers. "Second cancer risk following testicular cancer: a follow-up study of 1,909 patients." Journal of Clinical Oncology 11, no. 3 (March 1993): 415–24. http://dx.doi.org/10.1200/jco.1993.11.3.415.
Повний текст джерелаАнотація:
PURPOSE Improved survival in testicular cancer has been accompanied by concern about long-term side effects of therapy. We assessed the evolution of second cancer (SC) risk over a prolonged follow-up period, which has been rarely studied in large patient series. PATIENTS AND METHODS We estimated the risk of SCs in 1,909 patients with testicular cancer diagnosed in the Netherlands from 1971 to 1985. Complete medical information was obtained up to at least January 1988 for 92% of patients. Median follow-up was 7.7 years. For 89% of second tumors the diagnosis was confirmed through review of histologic slides; for an additional 8%, the diagnosis was verified by pathology reports only. RESULTS Seventy-eight patients developed a SC 1 year or more after start of treatment, as compared with 47.6 expected on the basis of incidence rates in the general population (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.1). The mean 15-year actuarial risk of all SCs was 9.8% (95% CI, 7.5% to 12.8%). Significantly increased RRs were observed for all gastrointestinal cancers combined (RR, 2.6; 95% CI, 1.7 to 3.9), stomach cancer (RR, 3.7; 95% CI, 1.8 to 6.8), contralateral testicular cancer (CLTC) (RR, 35.7; 95% CI, 21.8 to 55.2), and leukemia (RR, 5.1; 95% CI, 1.4 to 13.0). Patients who had received irradiation to the paraaortic lymph nodes and who survived testicular cancer for more than 5 years were at particularly high risk of developing stomach cancer (RR, 6.9; 95% CI, 3.3 to 12.7). The median interval between the diagnosis of testicular cancer and stomach cancer was 12.4 years. Patients treated with chemotherapy (CT) did not experience an increase in SCs in general. Indeed, CT-treated patients, as compared with those who received radiotherapy (RT), or surgery alone, had significantly reduced risk of CLTC. This finding might be attributed to an eradicating effect of CT on carcinoma in situ or subclinical CLTC. The excess risk of leukemia was not found to be clearly related to CT. CONCLUSION Testicular cancer patients who receive RT experience elevated risk of gastrointestinal tumors. CT does not seem to increase SC risk and may even decrease the risk of a CLTC. Following testicular cancer, the 15-year actuarial risk of all SCs is only about half the risk experienced by patients with Hodgkin's disease.
45
Dean, Robert M., Daniel H. Fowler, Nancy M. Hardy, Jeanne Odom, Kathleen Castro, Michael Krumlauf, Frances T. Hakim, Claude Sportes, Ronald E. Gress, and Michael R. Bishop. "Allograft T Cell Content Influences Early Engraftment after Reduced-Intensity Stem Cell Transplantation (RIST)." Blood 106, no. 11 (November 16, 2005): 3662. http://dx.doi.org/10.1182/blood.v106.11.3662.3662.
Повний текст джерелаАнотація:
Abstract Allogeneic hematopoietic stem cells (HSC) generally engraft rapidly and completely after myeloablative conditioning. However, with reduced-intensity conditioning (RIC), mixed chimerism and graft failure are more common. Host immune status and HSC number are factors known to affect engraftment after reduced-intensity stem cell transplantation (RIST). In addition, donor T cells within the allograft may also influencethe kinetics of donor engraftment after RIST. To evaluate this, we performed a controlled comparison of engraftment outcomes among 3 groups undergoing RIST, varying by ex vivo T cell depletion (TCD) or in vivo depletion of activated T cells with methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Group I (n = 50) received T cell replete (TCR) peripheral blood stem cells (PBSC) with cyclosporine (CSA) alone for GVHD prophylaxis. Group II (n = 17) received ex vivo TCD PBSC (positive/negative selection with T cell add-back to uniform dose of 1 x 105 CD3+ cells/kg) with CSA alone for GVHD prophylaxis. Group III (n = 31) received TCR PBSC with CSA plus MTX (5 mg/m2 IV x 4 doses) for GVHD prophylaxis. The 3 groups were similarly immunosuppressed from prior therapy before RIST (median absolute lymphocyte counts 330/μL, 260/μL, and 307/μL for Groups I, II, and III, respectively), and received an identical RIC regimen (fludarabine/cyclophosphamide) plus comparable numbers of filgrastim-mobilized PBSC from HLA-matched sibling donors (median 7.9 x 106, 7.6 x 106, and 6.8 x 106 CD34+ cells/kg, respectively; median 3.6 x 108, 1.0 x 105, and 3.2 x 108 CD3+ cells/kg, respectively). Hematopoietic recovery was slowest in Group III, consistent with the myelosuppressive effects of MTX (Table). A greater proportion of patients in Group I achieved complete donor chimerism (≥ 95%) by day +28 than in Groups II or III (P < 0.025), and at day +100, mixed donor chimerism persisted more often in Groups II and III than in Group I patients (P < 0.01). Correspondingly, early (< day +42) occurrence of grade 3–4 acute GVHD, before initiation of planned sequential donor lymphocyte infusions (DLI) in Group II, was more frequent in Group I than in either Groups II or III (p=0.08). Table: Hematopoietic Recovery, Engraftment, and GVHD Group Days to ANC > 500, median (range) Days to plt > 100, median (range) Donor chimerism ≥ 95% Early acute GVHD, grades 3–4 Day +28 Day +100 I 9 (7–13) 15.5 (12-42) 37/44 (84%) 36/38 (95%) 9/50 (18%) II 9 (7–10) 17.5 (11–40) 8/17 (47%) 9/14 (65%) 0/17 (0%) III 14 (7–21) 21.5 (12–85) 23/31 (74%) 21/31 (68%) 2/31 (6%) Thus, the deletion of T cells by either ex vivo TCD or in vivo MTX administration measurably alters the kinetics and degree of donor T cell engraftment after RIST. These observations provide evidence that donor T cells are an independent factor affecting engraftment of allogeneic HSC after RIST by compensating for incomplete host immune ablation. These data also support the hypothesis that a graft-versus-host effect plays a significant role in engraftment after RIST. Manipulation of donor T cells through graft engineering techniques may be a useful strategy to enhance engraftment in the setting of RIST.
46
Sasaki, Koji, Ildefonso Ismael Rodriguez-Rivera, Hagop M. Kantarjian, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Michael J. Burke, Patrick A. Zweidler-McKay, and Jorge E. Cortes. "Correlation of Lymphocyte Count with Treatment Response to Tyrosine Kinase Inhibitors in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase." Blood 124, no. 21 (December 6, 2014): 4538. http://dx.doi.org/10.1182/blood.v124.21.4538.4538.
Повний текст джерелаАнотація:
Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.
47
Bindi, Luca, and John A. Jaszczak. "Richardsite, Zn2CuGaS4, A New Gallium-Essential Member of the Stannite Group from the Gem Mines near Merelani, Tanzania." Minerals 10, no. 5 (May 20, 2020): 467. http://dx.doi.org/10.3390/min10050467.
Повний текст джерелаАнотація:
The new mineral richardsite occurs as overgrowths of small (50–400 μm) dark gray, disphenoidal crystals with no evident twinning, but epitaxically oriented on wurtzite–sphalerite crystals from the gem mines near Merelani, Lelatema Mountains, Simanjiro District, Manyara Region, Tanzania. Associated minerals also include graphite, diopside, and Ge,Ga-rich wurtzite. It is brittle, dark gray in color, and has a metallic luster. It appears dark bluish gray in reflected plane-polarized light, and is moderately bireflectant. It is distinctly anisotropic with violet to light-blue rotation tints with crossed polarizers. Reflectance percentages for Rmin and Rmax in air at the respective wavelengths are 23.5, 25.0 (471.1 nm); 27.4, 28.9 (548.3 nm); 28.1, 29.4 (586.6 nm); 27.7, 28.9 (652.3 nm). Richardsite does not show pleochroism, internal reflections, or optical indications of growth zonation. Electron microprobe analyses determine an empirical formula, based on 8 apfu, as (Zn1.975Cu0.995Ga0.995Fe0.025Mn0.010Ge0.005Sn0.005)Σ4.010S3.990, while its simplified formula is (Zn,Cu)2(Cu,Fe,Mn)(Ga,Ge,Sn)S4, and the ideal formula is Zn2CuGaS4. The crystal structure of richardsite was investigated using single-crystal and powder X-ray diffraction. It is tetragonal, with a = 5.3626(2) Å, c = 10.5873(5) Å, V = 304.46(2) Å3, Z = 2, and a calculated density of 4.278 g·cm−3. The four most intense X-ray powder diffraction lines [d in Å (I/I0)] are 3.084 (100); 1.882 (40); 1.989 (20); 1.614 (20). The refined crystal structure (R1 = 0.0284 for 655 reflections) and obtained chemical formula indicate that richardsite is a new member of the stannite group with space group I 4 ¯ 2 m . Its structure consists of a ccp array of sulfur atoms tetrahedrally bonded with metal atoms occupying one-half of the ccp tetrahedral voids. The ordering of the metal atoms leads to a sphalerite(sph)-derivative tetragonal unit-cell, with a ≈ asph and c ≈ 2asph. The packing of S atoms slightly deviates from the ideal, mainly due to the presence of Ga. Using 632.8-nm wavelength laser excitation, the most intense Raman response is a narrow peak at 309 cm−1, with other relatively strong bands at 276, 350, and 366 cm−1, and broader and weaker bands at 172, 676, and 722 cm−1. Richardsite is named in honor of Dr. R. Peter Richards in recognition of his extensive research and writing on topics related to understanding the genesis of the morphology of minerals. Its status as a new mineral and its name have been approved by the Commission of New Minerals, Nomenclature and Classification of the International Mineralogical Association (No. 2019-136).
48
Gugliotta, Luigi, Carlos Besses, Martin Griesshammer, Claire N. Harrison, Jean-Jacques Kiladjian, Ruth Coll, Jonathan Smith, Brihad Abhyankar, and Gunnar Birgegård. "Combination of Cytoreductive Therapies in Patients with Essential Thrombocythemia: A Preliminary Report From the E.X.E.L.S. Study." Blood 120, no. 21 (November 16, 2012): 2842. http://dx.doi.org/10.1182/blood.v120.21.2842.2842.
Повний текст джерелаАнотація:
Abstract Abstract 2842 Background: As some patients (pts) with essential thrombocythemia (ET) may discontinue their cytoreductive treatment because of drug intolerance/inefficacy, combinations of drugs with different activity/tolerability patterns are being utilized in clinical practice. Objectives: To evaluate the clinical relevance and patterns of cytoreductive combination treatment in ET in Evaluation of Xagrid™ Efficacy and Long-term Safety (EXELS), an observational study in 3643 European pts with high-risk ET. Patients and Methods: Data on pts receiving cytoreductive treatments in combination for ≥30 days (COMB) were collected from a planned data cut in September 2011. This timepoint was 2.5 years after enrollment completed. Results: COMB was recorded in 347 pts (9.5%), the vast majority (87.6%) of whom received anagrelide + hydroxycarbamide (ANA+HC). Other combinations were anagrelide + interferon-α (ANA+IFN), anagrelide + pipobroman (ANA+PIPO; Table). Six patients also received anagrelide + other drugs (ANA+OTH). In 333 pts, the initial drug was HC (n=167; 50.2%), ANA (n=138; 41.4%), IFN (n=14; 4.2%), PIPO (n=9; 2.7%), or OTH (n=5; 1.5%), while the added drug was ANA (n=195; 58.6%), HC (n=123; 36.9%), IFN (n=12; 3.6%), PIPO (n=2; 0.6%), or OTH (n=1; 0.3%). Fourteen pts started ANA+HC concomitantly. The median duration of monotherapy treatment before COMB start was 139 months for HC, 53 months for ANA, 71 months for IFN, and 237 months for PIPO. In pts receiving ANA+HC, the median weekly dose of the initial drug, both before and during COMB, was 10.5 mg for ANA and 7.0 g for HC, while the median weekly dose of the added drug during COMB was 7.0 mg for ANA and 3.5 g for HC. In these pts, the median platelet count ≤6 months before COMB start, during COMB (first test), and during COMB (last test) was 581, 411, and 434 ×109/L, respectively (with counts ≤600 ×109/L in 52.9%, 79.2%, and 77% of cases, respectively); the median white blood cell count was 6.9, 6.8, and 6.8 ×109/L, respectively; the median hematocrit was 38.0%, 36.3%, and 39.0%, respectively; and median hemoglobin was 11.9, 11.6, and 12.0 g/dL respectively. Similar laboratory results were obtained in pts receiving ANA+IFN or ANA+PIPO. Before, during and after COMB, anti-aggregatory treatment, usually low-dose aspirin, was given in 66.3%, 71.8%, and 33.1% of pts, respectively. In the same time periods, thrombotic (3, 11, and 11 cases, respectively) and hemorrhagic events (1, 2, and 5 cases, respectively) occurred. The COMB discontinuation rate was 54.5% globally (186/341 pts). COMB was discontinued by stopping ANA in 67 cases (36.0%), HC in 76 (40.9%), IFN in 8 (4.3%), PIPO in 4 (2.2%), both ANA and HC in 19 (10.2%), both ANA and IFN in 3 (1.6%), both ANA and PIPO in 3 (1.6%), or by adding a third drug in 6 cases (3.2%). In the 158 pts who discontinued ANA+HC, reasons were: intolerance/side effects (n=79, 50.0%), lack of efficacy (n=35, 22.2%), investigator decision (n=34, 21.5%, mainly with switch to ANA monotherapy), patient preference (n=10, 6.3%), missing, other (including economic) or unknown (n=17, 10.2%). Similarly, intolerance/side effects was the most frequent reason for discontinuing ANA+IFN (12/20; 60.0%). Overall, there were 63 patients with suspected severe adverse reactions (SSARs) and 45 with predefined events (PDEs) during COMB. The most frequent SSARs were myelofibrosis, palpitations, myocardial infarction and tachycardia. The most frequent PDEs included cardiovascular symptoms, myocardial infarction, stroke and transformation. Pts on COMB, the majority of whom received ANA+HC, accounted for 3.8% of all pts at registration and 5.0–5.8% of all pts in the following 5 years. Conclusion: COMB was performed in almost 10% of the 3643 pts with ET in the EXELS study, mainly with use of ANA+HC (87.6%). COMB appears to be a useful approach to treating patients for whom monotherapy was not well tolerated or ineffective since platelet levels were reduced to <600 ×109/L in almost 80% of pts, and a switch to monotherapy with the added drug, usually ANA, frequently followed. Disclosures: Gugliotta: Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Besses:Shire: Honoraria; Novartis: Honoraria. Griesshammer:Shire: Honoraria. Harrison:Novartis: Consultancy, Honoraria, Research Funding; YM Biosciences: Consultancy; S*Bio: Consultancy; Shire: Honoraria, Research Funding; Sanofi Avensis: Honoraria. Kiladjian:Shire: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Coll:Shire Pharmaceuticals: Employment. Smith:Shire Pharmaceuticals: Employment. Abhyankar:Shire Pharmaceuticals: Employment. Birgegård:Shire Pharmaceuticals: Honoraria; Pharmacosmos: Research Funding; Shire Pharmaceuticals Sweden: Consultancy.
49
Yoh, Kyung Ah, Ho Sup Lee, Lee Chun Park, Eun Mi Lee, Dae Jin Park, and Yang Soo Kim. "Prognostic Significance of Elevated Serum Ferritin Before Chemotherapy in Patients with Non-Hodgkin's Lymphoma." Blood 120, no. 21 (November 16, 2012): 5099. http://dx.doi.org/10.1182/blood.v120.21.5099.5099.
Повний текст джерелаАнотація:
Abstract Abstract 5099 Background: Elevated ferritin level before stem cell transplantation was documented an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation for hematologic malignancies. Until now, there have been reported few studies which suggested high serum ferritin level were associated with worse outcomes for lymphoma. The purpose of this study was to find the significance of high levels of serum ferritin for predicting survival outcome in patients with non-Hodgkin's lymphoma (NHL). Methods: A total of 267 patients who newly diagnosed and received an chemotherapy at the Kosin University Gospel Hospital, Busan, South Korea between September 1999 and April 2012 were enrolled retrospectively in the current study. Pretreatment serum ferritin was measured within 2 weeks before the beginning of first line chemotherapy. The enrolled diseases included diffuse large B cell lymphoma (DLBL, n=163, 61. 0%), T cell lymphoma (TCL, n=48, 18. 0%) and other lymphoma (n=56, 21. 0%) including mantle cell lymphoma, marzinal zone B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma and burkitt's lymphoma. In this study, patients with Hodgkin's disease and with undergoing chemotherapy 3 cycles or less than 3 cycles were excluded. Results: The median age of patients was 56 years (range, 14–84 years) and the mean level of serum ferritin at pre-treatment was 257. 79 ng/ml (range: 1. 70–6562. 00). In univariate anaylsis, factors associated with prolonged progression free survival (PFS) were LDH (p < 0. 001, 65. 8% in less than normal limit vs 39. 3% in more than normal limit), stage (p=0. 003, 64. 3% in less than stage III vs 46. 1% in stage III or more than), CRP (p = 0. 001, 58. 8% in less than 5mg/dL vs 27. 0% in 5mg/dL or more than), beta2-microglobulin (p < 0. 001, 59. 2% in less than 3. 5mg/L vs 29. 4% in 3. 5 mg/L or more than), and serum ferritin (p < 0. 001, 59. 2% in less than 500 ng/ml vs 22. 1% in 500 ng/ml or more than). Factors associated with prolonged overall survival (OS) were age (p < 0. 001, 61. 5% in less than 60 years vs 38. 4% in 60 years or more than), LDH (p < 0. 001, 70. 9% in less than normal limit vs 30. 0% in more than normal limit), ECOG performance status (p < 0. 001, 72. 8% in less than 2 scores vs 41. 9% in 2 scores or more than), stage(p=0. 005, 63. 4% in less than stage III vs 42. 1% in stage III or more than), Bulky mass (p = 0. 001, 57. 4% in tumor diameter less than 10cm vs 33. 5% in 10cm or more than), CRP (p = 0. 001, 60. 4% in less than 5mg/dL vs 27. 0% in 5mg/dL or more than), beta2-microglobulin (p < 0. 001, 59. 3% in less than 3. 5 mg/L vs 16. 3% in 3. 5 mg/L or more than), absolute lymphocyte count (p < 0. 001, 32. 2% in less than 1. 0 × 103/uL vs 59. 2% in 1. 0 × 103/uL or more than) and serum ferritin (p < 0. 001, 56. 9% in less than 500 ng/ml vs 23. 6% in 500 ng/ml or more than). In multivariate analysis, high level of LDH (RR (relative risk) = 0. 561, 95%CI: 0. 035–0. 890, P=0. 014), high level of beta2-microglobulin (RR= 0. 491, 95%CI: 0. 274–0. 880, P=0. 017) and high levels of serum ferritin (RR= 0. 557, 95%CI: 0. 311–0. 997, P=0. 049) were significant independent prognostic factors for PFS and high level of LDH (RR= 0. 418, 95%CI: 0. 269–0. 650, P < 0. 001), poor performance status (RR= 0. 467, 95%CI: 0. 295–0. 741, P=0. 001), high level of beta2-microglobulin (RR= 0. 461, 95%CI: 0. 278–0. 764, P=0. 003), and high levels of serum ferritin (RR= 0. 562, 95%CI: 0. 329–0. 958, P=0. 034) were significant independent prognostic factors for OS. Conclusions: High serum ferritin level of 500 ng/ml or more than 500 ng/ml may prognostic factor for survival outcomes including high LDH level, poor performance status, and high level of beta2-microglobulin in NHL. However, further studies are needed to confirm prognostic value of serum ferritn. Disclosures: No relevant conflicts of interest to declare.
50
Kim, Hawk, Elias Jabbour, Tapan Kadia, Gautam Borthakur, Sherry Pierce, Jianqin Shan, Jorge Cortes, et al. "A Prognostic Model of Therapy-Related Myelodysplastic syndrome ." Blood 114, no. 22 (November 20, 2009): 3796. http://dx.doi.org/10.1182/blood.v114.22.3796.3796.
Повний текст джерелаАнотація:
Abstract Abstract 3796 Poster Board III-732 Therapy-related myelodysplastic syndrome (Tx-MDS) is a poorly defined disease entity with in general a poor prognosis. The natural history of Tx-MDS is not well understood. In this analysis, we evaluated patient characteristics in an attempt to define the natural history and create a prognostic model of Tx-MDS. This analysis focuses on patients with Tx-MDS that have been previously treated for other malignancies. We identified a total of 438 patients who had a history of one or more malignancies prior to diagnosis of Tx-MDS evaluated at MD Anderson Cancer Center between 1997 to 2007. Finally, 281 Tx-MDS patients were selected by identifying those that had received prior chemotherapy (CTx) and/or radiation therapy (RTx) with a prior history of other malignancy, and by eliminating non-MDS entities from WHO classification such as RAEB-T. Patient characteristics are as follows: male sex was 165 (58.7%), median age at diagnosis of MDS was 66.2 years (range 13.4-89.4). IPSS was low in n=30 (11%), INT-1 in n=87 (31.0%), INT-2 in n=120 (42.7%) and high in n=35 (12.5%). The most common cytogenetic abnormality was -5 and/or -7 (n=149, 53.1%). Seventy five patients (26.7%) were diploid. Prior cancers included: head and neck (n=7, 2.5%), thyroid (n=3, 1.1%), lung (n=7, 2.5%), breast (n=32, 11.4%), gastrointestinal (n=13, 4.6%), prostate (n=34, 12.1%), other genitourinary or gynecological (n=16, 5.7%), melanoma/skin cancers (n=5, 1.8%), sarcomas (n=8, 2.8%), other solid cancers (n=2, 0.7%), lymphoma (n=102, 36.3%), CML/CLL (n=6, 2.1%), AML/ALL (n=5, 1.8%), multiple myeloma (n=11, 3.9%) and multiple cancers (n=30, 10.7%). Prior Tx was CTx only (n=107, 38.1%), RTx only (n=73, 26.0%) or both CTx and RTx (n=101, 35.9%). A total of 54 patients had received hematopoietic stem cell transplantation (HSCT) (autologous n=52 (18.5%); allogeneic n=2 (0.7%)). Potential prognostic factors were selected by univariate analyses and validated by multivariate analysis. The final prognostic factors were incorported into a prognostic model of Tx-MDS. We also evaluated the impact of specific forms of therapy in outcome in Tx-MDS. Univariate analyses for better survival revealed that presence of hepatomeglay (no hepatomegaly vs. hepatomegaly; Median 10.7 vs. 1.7 months (M); 95% confidence interval [CI] 0-5.8 vs. 8.7-12.7M; p=0.023), chromosome alterations (8+, 20q-, Y-, normal vs. others; median 22.1M vs. 8.2M ; 95% CI 17.0-27.2 vs. 6.9-9.5M; p<0.001), types of MDS by WHO classification (RA, RCMD, MDSu vs. others; median 22.4 vs. 8.8M; 95% CI 10.4-34.4 vs. 7.5-10.1M; p<0.001), time from Tx to MDS (≤6 vs. >6Y; median 13.3 vs. 10.6; 95% CI 5.4-21.2 vs. 6.8-14.4; p=0.027), treatment line(s) of therapy (1 vs. ≥2; median 14.4 vs. 8.6M; 95% CI 10.1-18.8 vs. 5.5-11.7M; p=0.011), serum albumin (≥4 vs. <4g/dL; median 14.4 vs. 9.1M; 95% CI 9.7-19.1 vs. 7.5-10.8m; p=0.005), serum beta2 microglobulin (≤3 vs. >3mg/L; median 12.2 vs. 9.1M; 95% CI 8.2-16.2 vs. 6.3-11.8M; p=0.015), serum creatitine (≤1 vs. >1mg/dL; median 11.9 vs. 10.2M; 95% CI 7.1-16.7 vs. 8.1-12.3M; p=0.061), ECOG performance status (0-1 vs. ≥2; median 11.8 vs. 5.5M; 95% CI 9.7-14.0 vs. 2.4-8.6M; p<0.001). Age (p=0.109), sex (p=0.862), prior Tx (CTx vs. RTx only; p=0.471), prior malignancies (hematological vs. solid cancer; p=0.650), prior lymphoma (p=0.958), prior HSCT (p=0.691) and serum ferritin level (p=0.420) were not significant. When incorporated into the multivariate model, only chromosomal alterations (HR=0.366) and WHO classification (HR=0.339) were significant prognostic factors. Based on this, we divided patients into three prognostic groups: good (n=38; no risk factor; median survival 33.8 months), intermediate (n=108; 1 risk factor; median survival 15.3 months) and poor (n=135; 2 risk factors; median survival 6.8 months). This model could predict time to acute leukemia transformation (events 2 vs. 12 vs. 18; p-value=0.017. In conclusion, we have developed a model that predicts for overall survival and time to acute leukemia transformation in Tx-MDS. This model will serve to develop risk-adapted therapeutic strategies. Disclosures: No relevant conflicts of interest to declare.