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1
Weijers, René E., Alphons G. H. Kessels, Geert H. I. M. Walenkamp, Henk van Mameren, and Gerrit J. Kemerink. "Effect of Tube Angulation on the Measurement of Intermetatarsal Angles." Journal of the American Podiatric Medical Association 95, no. 4 (July 1, 2005): 370–75. http://dx.doi.org/10.7547/0950370.
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We systematically investigated the effect of tube angulation on angular distortion of the anteroposterior radiograph of the foot. Three-dimensional data from the metatarsals originating from computed tomographic scans of ten healthy volunteers were projected onto the supporting surface at various tube angulations to simulate radiography. The distortion of the intermetatarsal angles decreased from 1.2° to 3.5° at 20° tube angulation to 0.4° to 2.7° at 0° tube angulation. The relatively small improvement in angular measurement using 0° instead of 15° tube angulation would not outweigh the adverse effects of changing the standard radiographic technique. Physician awareness of this source of error when planning surgical therapy seems more important. (J Am Podiatr Med Assoc 95(4): 370–375, 2005)
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Jessen, Marie, and Julie Mackenhauer. "Prævalens af lungeemboli hos synkoperede patienter." Dansk Tidsskrift for Akutmedicin 1, no. 1 (January 18, 2018): 12–13. http://dx.doi.org/10.7146/akut.v1i1.97265.
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Resume af originalartiklel vedr. prævalens af lungeemboli hos synkoperede patienterPrandoni P, Lensing AW, Prins MH, Ciammaichella M, Perlati M, Mumoli N, Bucherini E, Visona A, Bova C, Imberti D et al: Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope. N Engl J Med 2016, 375(16):1524-1531.
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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.
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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.
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Sanders, Lee J. "Jean-Martin Charcot (1825–1893)." Journal of the American Podiatric Medical Association 92, no. 7 (July 1, 2002): 375–80. http://dx.doi.org/10.7547/87507315-92-7-375.
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Jean-Martin Charcot was one of the most celebrated French physicians of the 19th century. A masterful teacher and a captivating lecturer, Charcot created the foundations of neurology as an independent discipline, and transformed the Salpêtrière hospital, in Paris, into one of the world’s greatest teaching centers for clinical neurologic research. His name is attached to the distinct pathologic entity, Charcot’s joint disease, that he so meticulously described. This article reviews the highlights of Charcot’s career and his clinicoanatomic studies of patients with tabetic arthropathies. (J Am Podiatr Med Assoc 92(7): 375-380, 2002)
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Williams, Michael D., Mugdha V. Joglekar, Anandwardhan A. Hardikar, and Wilson K. M. Wong. "Directed differentiation into insulin-producing cells using microRNA manipulation." Open Medicine 15, no. 1 (June 19, 2020): 567–70. http://dx.doi.org/10.1515/med-2020-0170.
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AbstractOur commentary is focused on three studies that used microRNA overexpression methods for directed differentiation of stem cells into insulin-producing cells. Islet transplantation is the only cell-based therapy used to treat type 1 diabetes mellitus. However, due to the scarcity of cadaveric donors and limited availability of good quality and quantity of islets for transplant, alternate sources of insulin-producing cells are being studied and used by researchers. This commentary provides an overview of distinct studies focused on manipulating microRNA expression to optimize differentiation of embryonic stem cells or induced pluripotent stem cells into insulin-producing cells. These studies have used different approaches to overexpress microRNAs that are highly abundant in human islets (such as miR-375 and miR-7) in their differentiation protocol to achieve better differentiation into functional islet beta (β)-cells.
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Classen, Albrecht. "The Romance of Thebes (Roman de Thèbes), trans. by Joan M. Ferrante and Robert W. Hanning. The French of England Translation Series (FRETS), 11. Tempe, AZ: Arizona Center for Medieval and Renaissance Studies, 2018, ix, 365." Mediaevistik 32, no. 1 (January 1, 2020): 432–33. http://dx.doi.org/10.3726/med.2019.01.101.
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Much of high medieval culture was deeply influenced by the reception of classical literature, as best represented by the genre of the romans antiques, the Roman de Thèbes, the Roman d’Enéas, and the Roman de Troie. These were based, in turn, on the Thebaid of Statius (92 C.E.), Vergil’s Aeneid (after 19 B.C.E.), and the story of Troy as retold by Dares Phrygias and Dictys Cretensis (in Greek, first century C.E., lost today; in Latin, fourth century C.E. [Dictys] and sixth century C.E. respectively [Dares]). Two of the most respected medieval French scholars, Joan M. Ferrante and Robert W. Hanning, now provide new access to the Roman de Thèbe through their English translation, which they have based on the personal copy owned by Henry Despenser (1370–1406), Bishop of Norwich, well known especially for his ruthless suppression of the Peasant Revolt in 1381. This manuscript is today housed in the British Library, London, under Add. 34114, fol. 164a-226d, and it was critically edited by Francine Mora-Lebrun with a facing page modern French translation in 1995. Ms. A (Paris, BnF, fr. 375) was recently edited by Luca di Sabatino (2016), which could not be consulted here for obvious reasons. Ms. C (Paris, BnF, fr. 784) was edited by Guy Reynaud de Lage in 1966, 1968, then re-edited along with a facing-page modern French translation by Aimé Petit in 2008).
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Koçer, Abdulkadir. "Headache Attack Similar to Paroxismal Hemicrania Seen During Flight." Aerospace Medicine and Human Performance 91, no. 4 (April 1, 2020): 373–75. http://dx.doi.org/10.3357/amhp.5540.2020.
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INTRODUCTION: Airplane headache (AH) is unique to plane travel and looks like a short duration migraine attack or paroxysmal hemicrania (PH) attack without any autonomic symptoms. Until now, there has been no documented association between AH and PH.CASE REPORT: We report a 50-yr-old healthy woman with a very severe and sudden pulsating headache located in the left frontal region with radiation into the left eye during takeoff which diminished within 10-15 min during her airplane journeys.DISCUSSION: The patient was diagnosed with AH and she had good response to indomethacin. The pain was unique to plane travel but looked like PH. We discuss the association between AH and PH attack in the light of diagnostic criteria and therapeutic approach in the report.Koçer A. Headache attack similar to paroxysmal hemicrania seen during flight. Aerosp Med Hum Perform. 2020; 91(4):373–375.
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Morewitz, Stephen J., Graham P. Shaw, Joel R. Clark, and Samantha Mullins. "A Survey of Podiatric Medical Students’ Computer Literacy." Journal of the American Podiatric Medical Association 94, no. 4 (July 1, 2004): 375–81. http://dx.doi.org/10.7547/0940375.
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This article reviews the extent of health-care students’ computer literacy and presents the results of a survey of podiatric medical students’ computer literacy. The results of this survey indicate that podiatric medical students are more likely than other health-care students to rate their computer literacy as good or very good. There was no gender difference in this self-reported computer knowledge. The implications for designing and using Web-based instructional materials and technology for podiatric medical students are discussed. (J Am Podiatr Med Assoc 94(4): 375–381, 2004)
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Zhao, Xin, Yun-dou Wang, Xiao-feng Zhang, Shu-tian Gao, Li-jun Guo, and Li-na Sun. "Research on Modularized Design and Allocation of Infectious Disease Prevention and Control Equipment in China." Disaster Medicine and Public Health Preparedness 11, no. 3 (November 15, 2016): 375–82. http://dx.doi.org/10.1017/dmp.2016.140.
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AbstractFor the prevention and control of newly emergent or sudden infectious diseases, we built an on-site, modularized prevention and control system and tested the equipment by using the clustering analysis method. On the basis of this system, we propose a modular equipment allocation method and 4 applications of this method for different types of infectious disease prevention and control. This will help to improve the efficiency and productivity of anti-epidemic emergency forces and will provide strong technical support for implementing more universal and serialized equipment in China. (Disaster Med Public Health Preparedness. 2017;11:375–382)
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Faast, R., L. F. S. Beebe, S. J. Harrison, S. M. McIlfatrick, R. J. Ashman, and M. B. Nottle. "33 USE OF ADULT MESENCHYMAL STEM CELLS FOR CLONING PIGS." Reproduction, Fertility and Development 18, no. 2 (2006): 125. http://dx.doi.org/10.1071/rdv18n2ab33.
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Current cloning efficiencies are relatively low and there is evidence to suggest that a less differentiated cell type can increase these (Jaenisch et al. 2002 Cloning and Stem Cells 4, 389-396). As part of an ongoing study that aims to develop cloning as a breeding tool for the pig industry, we examined whether mesenchymal stem cells (MSCs) isolated from bone marrow (Experiment 1) and blood (Experiment 2) could increase cloning efficiencies compared with fibroblasts isolated from ear tissue of live animals. MSCs were isolated from the femurs and blood of two pigs over a Histopaque-1077 density gradient. Cells were seeded and cultured in DMEM supplemented with 10% fetal bovine serum (FBS) and antibiotics/antimycotics. Blood MSCs were plated onto fibronectin-coated dishes (Faast and Nottle, Proc. Australian Health Med. Res. Congress 2004, abst. 1272). Cells from passages 2-4 were used for nuclear transfer by means of a fusion before being subjected to the activation protocol described previously (Harrison et al. 2004 Cloning and Stem Cells 6, 327-331). Embryos were cultured in a modified NCSU23 for 7 days. In Experiment 1 there was no difference in the number of fused embryos that cleaved in the bone marrow MSC and fibroblast groups (374/447; 84% vs. 370/446; 83%, respectively; 9 replicates). The number of embryos that developed to the blastocyst stage by day 7 was significantly higher in the bone marrow MSC group compared with the fibroblast group (136/447; 30% vs. 79/446; 18%, respectively, Chi square test; P < 0.01). In Experiment 2 there was no difference in the percentage of embryos that cleaved in the blood MSC and fibroblast groups (287/375; 77% vs. 275/347; 79%, respectively; 8 replicates). The number of embryos that developed to the blastocyst stage by day 7 was also similar between the blood MSC and fibroblast groups (67/375; 18% vs. 63/347; 18%, respectively). In conclusion, our results suggest that bone marrow MSCs may be a more efficient cell type, compared with fibroblasts, for the cloning of live animals.
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Tengs, Tammy O., Eric P. Winer, Susan Paddock, Omar Aguilar-Chavez, and Donald A. Berry. "Testing for the BRCA1 and BRCA2 Breast-Ovarian Cancer Susceptibility Genes." Medical Decision Making 18, no. 4 (October 1998): 365–75. http://dx.doi.org/10.1177/0272989x9801800402.
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Objective. The authors developed a Markov decision model to evaluate the health implications of testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes. Prophylactic measures considered included various combinations of immediate and delayed bilateral mastectomy and oophorectomy or taking no action. Methods. The model incorporated the likelihood of developing breast and/or ovarian cancer, survival, and quality of life. Parameter values were taken from public data bases, the published literature, and a survey of cancer experts. Outcomes considered were additional life expectancy and quality-adjusted life years (QALYs). Results are reported for 30-year-old cancer-free women at various levels of hereditary risk. Results and conclusions. The vast majority of women will not benefit from testing because their pre-test risks are low and surgical prophylaxis is undesirable. However, women who have family histories of early breast and/or ovarian cancer may gain up to 2 QALYs by allowing genetic testing to inform their decisions. Key words: BRCA1; BRCA2; ge netic testing; breast cancer; ovarian cancer; decision analysis. (Med Decis Making 1998;18:365-375)
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Labadie, Christian, Jing-Huei Lee, William D. Rooney, Silvia Jarchow, Monique Aubert-Frécon, Charles S. Springer, and Harald E. Möller. "Erratum to Myelin water mapping by spatially regularized longitudinal relaxographic imaging at high magnetic fields (Magn Reson Med 2014;71:375-387)." Magnetic Resonance in Medicine 74, no. 5 (September 2, 2015): 1503. http://dx.doi.org/10.1002/mrm.25974.
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Kreinin, Anatoly, Alexey Lyansberg, Miriam Yusupov, and Daniel S. Moran. "Fire Disaster Readiness: Preparation for the Evacuation of Medical Facilities During Fires in Haifa, Israel, 2016." Disaster Medicine and Public Health Preparedness 13, no. 02 (June 27, 2018): 375–79. http://dx.doi.org/10.1017/dmp.2018.53.
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AbstractWhen a fire occurs, there is little time to escape. In less than 30 seconds, a fire can rage out of control, filling the area with heat and toxic thick smoke (Purdue University Fire Department, 2017; http://www.purdue.edu/ehps/fire/fire-101.html.) In 2010, following the successful evacuation of Maale Ha’Carmel Mental Health Center during a raging forest fire in the area, a comprehensive investigation was performed to evaluate the management of the evacuation process and to systematically elicit lessons learned from the incident. In 2016, a forest fire erupted in the same geographic area that required the evacuation of Fliman Geriatric Rehabilitation Hospital, and methodical debriefing identified the strengths and weaknesses of the evacuation process in that hospital. The lessons learned from the evacuation of these two health care facilities, which were at the focus of major fires in Israel in 2010 and in 2016, are presented. (Disaster Med Public Health Preparedness. 2019;13:375–379)
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Hoelzer, Dieter, Wolfgang Hiddemann, Anita Baumann, Hartmut Döhner, Ulrich Dührsen, Rainer Fietkau, Martin-Leo Hansmann, et al. "High Survival Rate in Adult Burkitt’s Lymphoma/Leukemia and Diffuse Large B-Cell Lymphoma with Mediastinal Involvement." Blood 110, no. 11 (November 16, 2007): 518. http://dx.doi.org/10.1182/blood.v110.11.518.518.
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Abstract With short intensive chemotherapy mainly based on HDMTX, fractionated alkylators and HDAC outcome of Burkitt’s NHL and mature B-ALL (B-ALL) in adults could be improved substantially to CR rates of 80% and overall survival (OS) of 50–70% (Hoelzer et al, Blood, 1996). Further intensification - namely increase of MTX dose - failed to improve these results. Therefore the German Multicenter Study Group for Adult ALL (GMALL) invented in 2002 a new protocol for mature B-ALL/Burkitt and other high-grade NHL, namely primary mediastinal (med) DLBCL, including 6x Rituximab® 375 mg/m2 before each chemo cycle and two R maintenance cycles. In addition 2 cycles based on HDAC 2 g /m2 were included. HDMTX was 1,5 g/m2 in the protocol for younger pts (<55 yrs). Older pts (>55 yrs) received a dose reduced regimen without HDAC and with MTX at 500 mg/m2. 227 pts with Burkitt (27=Burkitt-like), B-ALL or med DLBCL aged between 16 and 78 enrolled between 09/02 and 12/06 were evaluable for response after the first two cycles. The median age was 36 yrs for Burkitt, 46 for B-ALL and 35 for med DLBCL; 18%, 41% and 12% were older than 55 yrs respectively. The subgroups were characterised as follows: 115 Burkitt (stage III–IV 52%, extranodal inv. 78%, aaIPI >1 47%), 70 B-ALL, 42 med DLBCL (stage III–IV 55%, extranodal inv. 71%, aaIPI >1 61%). The CR rate was 90% in Burkitt, 83% in B-ALL and 69% in med DLBCL; death under therapy occurred in 3%, 11% and 0% respectively. The overall survival at 3 yrs was 91% for Burkitt, 79% for B-ALL and 90% for med DLBCL in pts at the age of 15–55 yrs and 84%, 39% and 67% (N=5) respectively in pts >55 yrs. CNS relapses were observed in 3 out of 22 older CR patients with B-ALL whereas in younger pts the CNS relapse rate was 0. CNS relapses are among the reasons for inferior outcome in elderly B-ALL in contrast to elderly pts with Burkitt or med DLBCL. CNS relapse rate may hopefully be reduced by inclusion of an intermediate dose ARAC cycle in the elderly B-ALL. There was no difference in OS between pts with Burkitt (92%) vs Burkitt-like NHL (86%). Since no prognostic factors could be identified in younger pts, there was no need for SCT in CR1. Major grade III/IV toxicity was hematological (28–37%) and mucositis (36%, 37%, 28% in cycles A1, B1, C1 respectively). Compared to the previous GMLL trial B-NHL90 (without Rituximab) with 270 pts the OS of 272 patients (including LBL, LCAL, DLBCL) at 3 yrs improved significantly from 54% to 80% (p<.0001) overall, 56% to 85% (p<.0001) in younger and 39% to 65% (p=.01) in older pts. In this largest prospective study of adult Burkitt’s lymphoma/leukemia and med DLBCL the combination of Rituximab and 6 short intensive chemo cycles was feasible and lead to an OS of 90% in NHL and 79% in mature B-ALL in the younger patient cohort. Even in older pts with Burkitt’s NHL survival was 84%. The further aim is now to reduce toxicity, namely mucositis.
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Lurain, Kathryn, Thomas S. Uldrick, Priscila H. Goncalves, Ramya Ramaswami, Mark N. Polizzotto, Anaida Widell, Seth M. Steinberg, et al. "Radiation-Sparing Treatment of HIV-Related Primary Central Nervous System Lymphoma with Antiretroviral Therapy, Rituximab and High-Dose Methotrexate." Blood 132, Supplement 1 (November 29, 2018): 2963. http://dx.doi.org/10.1182/blood-2018-99-112169.
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Abstract BACKGROUND: HIV-associated primary central nervous system lymphoma (HIV-PCNSL) is an AIDS-defining cancer. Tumors occur in patients with very low CD4+ counts, and tumors are almost always Epstein-Barr virus (EBV) infected. Overall survival (OS) has improved over time with antiretroviral therapy (ART)-associated immune reconstitution but is still generally less than 1 year. Treatment has traditionally included whole brain radiation, which can lead to devastating long-term neurotoxicity, including cognitive decline. ART has made it possible to treat patients with curative-intent, but radiation-sparing approaches have not been studied prospectively in HIV-PCNSL. METHODS: In a prospective phase II pilot study conducted in the HIV & AIDS Malignancy Branch at the National Cancer Institute, we evaluated curative-intent radiation-sparing immunochemotherapy in patients with untreated HIV-PCNSL (NCT00267865). Patients with HIV-PCNSL received ART, rituximab (375 mg/m2) and HD-MTX (6 g/m2) with leucovorin rescue (R-HD-MTX). Responses were evaluated by modified International Working Group Response Criteria for PCNSL after 6 cycles of induction R-HD-MTX and patients with a complete response (CR) received 2 consolidation cycles of R-HD-MTX. Patients with poor renal or cardiac function who were not eligible to receive HD-MTX at enrollment, received ART, rituximab and best-available radiation-sparing care. The primary objective of the study was to estimate the percentage of patients receiving ART and R-HD-MTX alive without recurrent lymphoma at two years. Response to treatment, immune reconstitution, and OS were evaluated using descriptive statistics and Kaplan-Meier methodology. RESULTS: Twelve patients were enrolled between September 2006 and June 2016. One enrolled patient was initially ineligible to receive HD-MTX due to renal dysfunction and received rituximab with temozolomide (TMZ) 150 mg/m2 for 5 days for one cycle followed by 6 cycles of R-HD-MTX + TMZ and 2 consolidation cycles of R-HD-MTX. Patient characteristics: 9 men, 3 women; median (med) age 33 years (range: 21-55); 8 African-American, 3 Hispanic, 1 white non-Hispanic; med Eastern Cooperative Oncology Group performance status 2 (1-3); med baseline Mini Mental State Examination (MMSE, maximum score = 30) was 22 (range: 5-29). Only 4 patients were on ART prior to diagnosis, and all but 1 had been on ART less than 4 months. Med time from HIV infection to PCNSL diagnosis was 30 weeks (range: 0-23 years). Med CD4+ T-cell count at PCNSL diagnosis was 16 cells/µL (0-409). Diagnosis of PCNSL was biopsy-confirmed (11) or made by 18fludeoxyglucose positron emission tomography/cerebral spinal fluid (CSF) EBV viral load criteria (1). 11/12 tumors were EBV positive. Flow cytometry showed leptomeningeal disease in 4 patients. Three had concurrent CNS infections, including Cryptococcus, histoplasmosis, and CMV retinitis. Ten were evaluable for response to R-HD-MTX induction. Two patients received only 1 cycle of therapy and were not evaluable due to treatment failure (TF). Responses after R-HD-MTX induction: CR (5), partial response (PR) (4) and progressive disease (PD) (1). Two patients with a PR received second-line TMZ at end of R-HD-MTX and obtained a subsequent CR. The patient with PD received second-line therapy with the Cancer and Leukemia Group B 50202 induction regimen and obtained a subsequent CR. There were 4 deaths on study: 1 pulmonary embolism, 1 CNS fungal infection in setting of PD, 2 TF. Eight patients (67%), including 3 patients who received second line therapy, obtained a durable CR. Med CD4+ T-cell increase following R-HD-MTX induction was +35 cells/uL (range: -54 - +369). In surviving patients, med MMSE after R-HD-MTX was 28 (27-30). For all patients, estimated 60-month OS was 66% (95% CI: 32-86%) with med potential follow-up of 82 months. Med OS was not reached. CONCLUSIONS:Treatment with ART and R-HD-MTX is associated with a high response rate, CD4+ immune reconstitution, preserved cognition, and improved OS, even in a high-risk patient population. Disclosures Uldrick: Celgene: Patents & Royalties: 10,001,483 B2; Celgene: Research Funding; Merck: Research Funding. Yarchoan:NIH: Patents & Royalties: Patents on IL-12 for KS and cereblon-binding drugs for KSHV diseases. Spouse has patent on KSHV IL-6. Patents assigned to DHHS/NIH.; Celgene Corp.: Research Funding.
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Gofur, Md Royhan. "Recent advances on identification of spermatogonial stem cells and their niche." Asian Journal of Medical and Biological Research 6, no. 3 (October 17, 2020): 375–82. http://dx.doi.org/10.3329/ajmbr.v6i3.49785.
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Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis. A balance between the self-renewal and differentiation of SSCs, strictly controlled in a special „niche‟ microenvironment in the seminiferous tubules (SSC niche), is essential to maintain normal spermatogenesis. Since the 1950s, many experimental methods, including histology, immunostaining, whole-mount analyses, and pulse-chase labeling, had been used in attempts to identify SSCs. Recent studies demonstrate that Aundiffseem to possess variable levels of stem cell potential to act as SSCs; GFRα1+ population in As has the greatest potential to act as SSCs (can consider as actual SSCs) whereas NGN3+ population in Aundiffhas comparatively much lower potential to act as SSCs (can consider as potential SSCs). The precise identity of SSCs is still being refined. Sertoli cells, directly interact with SSCs, and interstial cells including Leydig cells, testicular macrophages, peritubularmyoid cells and vascular smooth muscle cells, control the proliferation and differentiation of SSCs through the secretion of extrinsic factors, constitute the cellular components of SSC niche which preferentially locates in the region of seminiferous tubules adjacent to the interstitium that always coincide blood vessels.
Asian J. Med. Biol. Res. September 2020, 6(3): 375-382
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Herrero, Joaquin, Jose Gómez-Codina, Mariano Provencio, Antonio Rueda, Pilar Sabin, Marta Llanos, Francisco Lobo, David Vicente, and Francisco Ramon Garcia Arroyo. "Biweekly regimen of nonpegylated liposomal doxorubicin with cyclophosphamide, vincristine, and prednisone plus rituximab (R-COMP-14) as primary treatment for diffuse large B-cell lymphoma (DLBCL): Long-term follow-up of a phase II study." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 8062. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.8062.
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8062 Background: To evaluate the efficacy and toxicity of dose-dense biweekly schedule of (R-COMP-14) in patients newly diagnosed of agrressive diffuse B cell lymphomas (DLBCL). Methods: In this single-arm, open-label, multicenter trial, 60 pts were included between 2004 to 2008. Received rituximab (375 mg/m2) D1 + cyclophosphamide (750 mg/m2)D1 + vincristine (1.4 mg/m2; max. 2 mg)D1 + prednisone (100 mg/d D1 and D5) and non-pegylated liposomal doxorubicin (50 mg/m2) every two weeks. Response was assessed at cycle 3, and patients with complete or partial response received 5 additional courses. Granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim was administered on day 2. The primary efficacy endpoint was (CR) and objective response rate (ORR). Survival follow-up data were updated. Results: 59 evaluable patients with a median age of 50 years (21-65) were analyzed. Clinical Characteristics: 22 Pts stage I-II (aaIPI≥1 (37%), 17 (29%) stage III, and 19 (32%) in stage IV. aaIPI=1 41(67%), aaIPI2/3= 18(33%).LVEF basal: 65,5[50-93]. Extra-nodal disease: 42%. B symptoms: 44.1%. The mean calculated dose intensities of cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and rituximab were 98,7%, 98,7%, 76,1% and 98,3% respectively. Among 60 eligible patients (96,7% completed six cycles and 74,4% completed all eight cycles. ORR was 81%, and CR rate of 54,2%. IC 95% [40,7-67,8]. The main toxicity was neutropenia Gr=III-IV/ and febrile neutropenia in 20% of patients. Neurotoxicity Gr=III-IV in 3,4%. No cardiac toxicity Gr: III-IV was reported. No toxic deaths. After a median follow-up of 25-64m(44m) the 5-year overall survival (OS), event-free survival, (EFS) and disease free survival (DFS) were 80%, 67%, and 77% respectively. Forty two patients (71%) had (<60 y) and med. OS(p=0,017) and med EFS(p=0,014) was 72,3% and 68,1 in aaIPI=1 and 50,4% and 33,8 in aaIPI>1. Conclusions: Dose dense R-COMP-14 is an effective regimen in patients with (DLBCL) comparable o R- CHOP-14. Good tolerability profile with no Gr: III-IV cardiac toxicity or reduction of LVEF.
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Beyer, Andreas M., Marcelo G. Bonini, and Javid Moslehi. "Cancer therapy-induced cardiovascular toxicity: old/new problems and old drugs." American Journal of Physiology-Heart and Circulatory Physiology 317, no. 1 (July 1, 2019): H164—H167. http://dx.doi.org/10.1152/ajpheart.00277.2019.
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Cardio-oncology has emerged as an exciting new field at the intersection of cardiology and oncology. While improved oncology treatment efficacy has increased survival rates in cancer patients, the long-term cardiovascular consequences of this life-saving treatment have become more clinically relevant. Both traditional and newer (targeted) cancer therapies can have cardiovascular and metabolic sequelae, resulting in heart failure, coronary artery disease, myocarditis, pericardial disease, hypertension, and vascular and metabolic perturbations (Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med 375: 1457–1467, 2016). Both acute and chronic cardiovascular toxicities have proven challenging for clinicians and patients, significantly contributing to morbidity and mortality. Although chronic cardiovascular disease affects a growing number of cancer survivors (~17 million in the United States in 2019), cardiovascular toxicities associated with cancer and cancer therapies are poorly understood mechanistically. To balance potential damage to the cardiovascular system with effective and efficient cancer treatment, novel strategies are sorely needed. This perspective focuses on an assembly of articles that discuss novel means of counteracting adverse cardiovascular events in response to anticancer therapy. In light of new clinical syndromes in cardiology due to cancer therapies, we hope to highlight promising research opportunities offered by cardio-oncology (Bellinger AM, Arteaga CL, Force T, Humphreys BD, Demetri GD, Druker BJ, Moslehi JJ. Cardio-oncology: how new targeted cancer therapies and precision medicine can inform cardiovascular discovery. Circulation 132: 2248–2258, 2015.).
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Islamiyah, Roudlotul, and Suparno. "Teacher Knowledge in Early Childhood Gender Education." JPUD - Jurnal Pendidikan Usia Dini 13, no. 2 (December 6, 2019): 327–40. http://dx.doi.org/10.21009/jpud.132.09.
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The industrial development era 4.0, many threats lurk children in the form of bad influence through books, videos, or other media and become a challenge for parents and teachers. Gender education and the introduction of personal identity are important given early on. This study aims to determine the effect of teacher knowledge on the implementation of gender education in early childhood. This research uses quantitative survey research methods with a simple linear regression design for data analysis. The respondents were 34 early childhood education teachers. The results show the data with the conclusion that the calculated value> t table and p-value (sig) of 0.001 (<0.05) which means that there is a significant influence on teacher knowledge about early childhood gender education. Research suggests about how to improve gender education in early childhood education and create learning modules for early childhood teacher guidance.
Keywords: Early gender education, Teacher knowledge about gender education
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Weber, Donna M., Michael Wang, Kay B. Delasalle, Maria Gavino, and Raymond Alexanian. "2-Chlorodeoxyadenosine (2-CdA) and Cyclophosphamide (Cy) Alone or in Combination with Rituximab (Rit) for Previously Untreated Waldenstrom’s Macroglobulinemia (WM)." Blood 104, no. 11 (November 16, 2004): 1476. http://dx.doi.org/10.1182/blood.v104.11.1476.1476.
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Abstract Between 3/96-11/03 we treated 62 consecutive, newly diagnosed pts with symptomatic WM with either 2-CdA 1.5 mg/m2 sc tid x 7d + Cy 40 mg/m2 po bid x 7d (35 pts, 3/96-2/99) or with identical doses of 2-CdA and cyclophosphamide + Rit 375 mg/m2 IV q wk x 4 wk (27 pts, 11/98-11/03). For both regimens a second and final course was repeated after 6 weeks. Partial response (PR), defined by at least 50% reduction of monoclonal IgM, adenopathy, and organomegaly, was noted in 83% (29 pts) of pts treated with 2-CdA-Cy and 81% (22 pts) with 2-CdA-Cy-Rit; complete disappearance of clonal evidence of disease (CR) by negative serum and urine immunofixation, bone marrow, and CT scan was noted in 6% (2 pts) treated with 2-CdA-Cy and 11% (3 pts) with 2-CdA-Cy-Rit. Overall response rate was 89% and 93% for 2-CdA-Cy and 2-CdA-Cy-Rit, respectively. Responding patients were followed without further treatment until relapse, defined by a 25% increase in M-protein from nadir, or recurrence of adenopathy or organomegaly. Median time to remission was similar at 2.5 mos for 2-CdA-Cy and 2.4 months for 2-CdA-Cy-Rit (p.42), but time to treatment failure (TTF) appeared longer for 2-Cda-Cy-Rit (med. 64.2 mos) than for 2-CdA-Cy (med. 31.4 mos) (p.20). Since many pts have not required retreatment for symptomatic disease at the time of relapse, we also evaluated time to retreatment (TTRT) as a separate endpoint. The median time to retreatment (TTRT) has not been reached with 2-CdA-Cy-Rit, in comparison with a median TTRT of 51.2 mos with 2-CdA-Cy (p<.01), illustrating the prolonged period of stability after limited treatment with either 2-CdA combination and the superiority of added rituximab. Median overall survival has not been reached with either regimen since only 27% of all pts have died. Both treatment regimens were associated with minimal toxicity, high response rate, long duration of unmaintained remission, even longer time to the need for retreatment, and long survival. Thus treatment with a limited 2-CdA regimen represents the therapy of choice, in our opinion, for previously untreated, symptomatic WM.
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Risal, A., and P. P. Sharma. "Psychiatric Illness in the Paediatric Population Presenting to a Psychiatry Clinic in a Tertiary Care Centre." Kathmandu University Medical Journal 8, no. 4 (June 5, 2012): 375–81. http://dx.doi.org/10.3126/kumj.v8i4.6235.
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Background A variety of psychiatric manifestations can be seen in children below the age of 18 years. Such cases rarely present directly to psychiatric care. Methods Retrospective study in Tertiary care hospital . The study population included all the patients of paediatric age group presenting to Psychiatry Outpatient Department of Dhulikhel Hospital directly or referred by a paediatrician or other specialists from October 2008 to October 2010. Results Among the paediatric population evaluated in the psychiatry clinic for two years from October 2008 to October 2010 (N=168), 66.7% were in the age group 15-18 years {mean = 14.77 (±2.99)}, 71.4% were female and 42.3% belonged to Brahmin cast. The highest number of (15%) patients was seen during the month of August 2010. Six months analysis of the psychiatric illnesses of the patients from April 2010 up to October 2010 (n=80) showed dissociative disorder (15%), and seizure disorder (15%) to be the most common diagnoses, followed by depressive disorder and intentional self harm (ISH) (13.8% each). 15% of patients were found to be treated by magico-religious means, with the majority of patients (66.7%) diagnosed as having dissociative disorder. Conclusion The majority of the paediatric population presenting to a psychiatry clinic were in the age group 15-18 years and of female sex. Dissociative disorder was the most common diagnosis followed by depressive disorders. The majority of patients with dissociative disorder had previously been treated by magico-religious means.http://dx.doi.org/10.3126/kumj.v8i4.6235 Kathmandu Univ Med J 2010;8(4):375-81
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Lowe, Calvin G., Rashida T. Campwala, Nurit Ziv, and Vincent J. Wang. "The Broselow and Handtevy Resuscitation Tapes: A Comparison of the Performance of Pediatric Weight Prediction." Prehospital and Disaster Medicine 31, no. 4 (May 25, 2016): 364–75. http://dx.doi.org/10.1017/s1049023x16000455.
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AbstractObjectivesTo assess the performance of two pediatric length-based tapes (Broselow and Handtevy) in predicting actual weights of US children.MethodsIn this descriptive study, weights and lengths of children (newborn through 13 years of age) were extracted from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Using the measured length ranges for each tape and the NHANES-extracted length data, every case from the study sample was coded into Broselow and Handtevy zones. Mean weights were calculated for each zone and compared to the predicted Broselow and Handtevy weights using measures of bias, precision, and accuracy. A sub-sample was examined that excluded cases with body mass index (BMI)≥95th percentile. Weights of children longer than each tape also were examined.ResultsA total of 3,018 cases from the NHANES database met criteria. Although both tapes underestimated children’s weight, the Broselow tape outperformed the Handtevy tape across most length ranges in measures of bias, precision, and accuracy of predicted weights relative to actual weights. Accuracy was higher in the Broselow tape for shorter children and in the Handtevy tape for taller children. Among the sub-sample with cases of BMI≥95th percentile removed, performance of the Handtevy tape improved, yet the Broselow tape still performed better. When assessing the weights of children who were longer than either tape, the actual mean weights did not approximate adult weights; although, those exceeding the Handtevy tape were closer.ConclusionsFor pediatric weight estimation, the Broselow tape performed better overall than the Handtevy tape and more closely approximated actual weight.LoweCG, CampwalaRT, ZivN, WangVJ. The Broselow and Handtevy resuscitation tapes: a comparison of the performance of pediatric weight prediction. Prehosp Disaster Med. 2016;31(4):364–375.
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Jain, Trevor, Aaron Sibley, Henrik Stryhn, and Ives Hubloue. "Comparison of Unmanned Aerial Vehicle Technology-Assisted Triage versus Standard Practice in Triaging Casualties by Paramedic Students in a Mass-Casualty Incident Scenario." Prehospital and Disaster Medicine 33, no. 4 (July 13, 2018): 375–80. http://dx.doi.org/10.1017/s1049023x18000559.
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AbstractIntroductionThe proliferation of unmanned aerial vehicle (UAV) technology has the potential to change the way medical incident commanders (ICs) respond to mass-casualty incidents (MCIs) in triaging victims. The aim of this study was to compare UAV technology to standard practice (SP) in triaging casualties at an MCI.MethodsA randomized comparison study was conducted with 40 paramedic students from the Holland College Paramedicine Program (Charlottetown, Prince Edward Island, Canada). Using a simulated motor vehicle collision (MVC) with moulaged casualties, iterations of 20 students were used for both a day and a night trial. Students were randomized to a UAV or a SP group. After a brief narrative, participants either entered the study environment or used UAV technology where total time to triage completion, GREEN casualty evacuation, time on scene, triage order, and accuracy were recorded.ResultsA statistical difference in the time to completion of 3.63 minutes (95% CI, 2.45 min-4.85 min; P=.002) during the day iteration and a difference of 3.49 minutes (95% CI, 2.08 min-6.06 min; P=.002) for the night trial with UAV groups was noted. There was no difference found in time to GREEN casualty evacuation, time on scene, or triage order. One-hundred-percent accuracy was noted between both groups.Conclusion:This study demonstrated the feasibility of using a UAV at an MCI. A non-clinical significant difference was noted in total time to completion between both groups. There was no increase in time on scene by using the UAV while demonstrating the feasibility of remotely triaging GREEN casualties prior to first responder arrival.Jain T, Sibley A, Stryhn H, Hubloue I.Comparison of unmanned aerial vehicle technologyassisted triage versus standard practice in triaging casualties by paramedic students in a mass-casualty incident scenario. Prehosp Disaster Med. 2018;33(4):375–380
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Kaufman, Jonathan L., Saad Z. Usmani, Jesús San-Miguel, Nizar Bahlis, Darrell J. White, Lotfi Benboubker, Gordon Cook, et al. "Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM)." Blood 134, Supplement_1 (November 13, 2019): 1866. http://dx.doi.org/10.1182/blood-2019-123483.
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Introduction: Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, is approved in combination with standard-of-care regimens for the treatment of newly diagnosed multiple myeloma (NDMM) and RRMM. When combined with standard of care regimens across four phase 3 studies, daratumumab demonstrated ≥44% reductions in the risk of progression or death, nearly doubled complete response (CR) or better rates, and tripled minimal residual disease (MRD)-negative rates at the 10-5 sensitivity threshold in pts with RRMM or NDMM (Palumbo A, et al. N Engl J Med 2016. 375[8]:754-766; Dimopoulos MA, et al. N Engl J Med 2016. 375[14]:1319-1331; Mateos MV, et al. N Engl J Med 2018. 378[6]:518-528; Facon T, et al. N Engl J Med 2019. 380[22]2104-2015). In the phase 3 POLLUX study (median follow-up 44.3 months), D-Rd reduced the risk of disease progression or death by 56% and significantly increased the overall response rate (ORR) versus Rd alone (93% vs 76%; P <0.0001) in patients (pts) with RRMM. Here, we present updated efficacy and safety analyses of POLLUX after >4 years of median follow-up. Methods: Pts who received ≥1 prior line of therapy were randomized (1:1) to Rd (lenalidomide 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone 40 mg per week) ± daratumumab (16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, then Q4W until disease progression). Cytogenetic risk was determined by local fluorescence in situ hybridization or karyotyping; pts with high cytogenetic risk had t(4;14), t(14;16), and del17p abnormalities. PFS on subsequent line of therapy (PFS2), an exploratory endpoint, was defined as time from randomization to progression after next line of subsequent therapy or death. Results: A total of 569 pts were randomized (D-Rd, n = 286; Rd, n = 283). At a median follow-up of 51.3 months, D-Rd significantly prolonged progression-free survival (PFS) versus Rd (median 45.8 vs 17.5 months; hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.35-0.54; P <0.0001; Figure). D-Rd also prolonged PFS versus Rd among pts with 1 prior line of therapy, among pts with 1-3 prior lines of therapy, and regardless of cytogenetic risk status (Table). A PFS benefit with D-Rd was also observed among pts who received prior lenalidomide (median 38.8 vs 18.6 months; HR, 0.34; 95% CI, 0.19-0.59; P <0.0001) and among pts refractory to bortezomib (median 34.3 vs 11.3 months; HR, 0.41; 95% CI, 0.25-0.68; P = 0.0004). D-Rd was associated with a significantly higher ORR versus Rd (93% vs 76%), including higher rates of ≥very good partial response (81% vs 49%) and ≥CR (57% vs 24%; all P <0.0001). Median time to next therapy for D-Rd versus Rd was not reached in the D-Rd group versus 22.8 months in the Rd group (HR, 0.39; 95% CI, 0.30-0.49; P <0.0001). D-Rd significantly prolonged PFS2 versus Rd (median 53.3 vs 31.6 months; HR, 0.54; 95% CI, 0.43-0.68; P <0.0001). In the D-Rd group, 121 deaths were observed versus 133 deaths in the Rd group; follow-up for overall survival is ongoing. The median duration of treatment was 34.3 months in the D-Rd arm versus 16.0 months in the Rd arm. The most common (≥10%) grade 3/4 treatment-emergent adverse events (TEAEs) observed with D-Rd versus Rd included neutropenia (56% vs 42%), anemia (18% vs 22%), thrombocytopenia (15% vs 16%), pneumonia (16% vs 10%), and diarrhea (10% vs 4%). Similar rates of discontinuations due to TEAEs were observed for D-Rd versus Rd (16% vs 15%). The incidence of invasive second primary malignancies was 4.9% and 5.7% for the D-Rd and Rd groups, respectively. Additional efficacy data, including minimal residual disease, and safety analyses will be presented at the meeting. Conclusion: After >4 years of median follow-up, D-Rd continues to demonstrate a significant PFS benefit and higher rates of deeper responses versus Rd alone in pts with RRMM. Although significant PFS benefit was observed with D-Rd in RRMM pts regardless of prior lines of therapy or cytogenetic risk status, the greatest benefit was observed when used in patients treated earlier with D-Rd. The significant improvement in PFS2 suggests a potential survival benefit, but OS data is still immature. No new safety concerns were identified with this additional follow-up. Disclosures Kaufman: Celgene: Consultancy; Winship Cancer Institute of Emory University: Employment; Takeda: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; AbbVie: Consultancy; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy; Amgen: Consultancy. Usmani:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, SkylineDX, Takeda: Other: Consultant/Advisor; Amgen, Celgene, Janssen, Sanofi, Takeda: Speakers Bureau; Amgen Array Biopharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Pharmacyclics, Sanofi, Takeda: Other: Research Grant. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Bahlis:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. White:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Cook:Amgen, Bristol-Myers Squib, GlycoMimetics, Seattle Genetics, Sanofi: Honoraria; Janssen, Takeda, Sanofi, Karyopharm, Celgene: Consultancy, Honoraria, Speakers Bureau; Celgene, Janssen-Cilag, Takeda: Honoraria, Research Funding. Ho:Novartis: Other: Trial Investigator meeting travel costs; La Jolla: Other: Trial Investigator meeting travel costs; Janssen: Other: Trial Investigator meeting travel costs; Celgene: Other: Trial Investigator meeting travel costs. Moreau:Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Krevvata:Janssen: Employment. Pei:Janssen: Employment, Equity Ownership. Ukropec:Janssen: Employment, Equity Ownership. Renaud:Janssen: Employment, Equity Ownership. Trivedi:Janssen: Employment, Equity Ownership. Kobos:Janssen: Employment. Dimopoulos:Sanofi Oncology: Research Funding.
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Nguyen, My L., Catherine Burdalski, Syed Abbas Ali, Lindsay Kohler, and Steven Gilmore. "Prevention and Management of Daratumumab Mediated Infusion Related Hypersensitivity Reactions Pre-and Post-Implementation of Rapid Infusion Protocol." Blood 134, Supplement_1 (November 13, 2019): 5811. http://dx.doi.org/10.1182/blood-2019-125391.
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Background: Multiple Myeloma (MM) is defined as a clonal proliferation of malignant bone marrow plasma cells with high and uniform expression of CD 38 (Kumar et al, J Natl Compr Canc Netw. 2019; 3 and Lin et al, Am J Clin Pathol. 2004; 121:482-488). Daratumumab, a human IgGk monoclonal antibody, targets and binds to CD38, induces antibody dependent cell mediated cytotoxicity, complement activation, and antibody mediated phagocytosis (Prescribing information. Daratumumab; Janssen Biotech, Inc 2016). Daratumumab is associated with infusion related reactions (IRRs), which present with symptoms of rhinitis, cough, dyspnea, bronchospasm, chills and nausea. In two phase 3 trials, CASTOR (Palumbo et al, N Engl J Med. 2016; 375:754-66) and POLLUX (Dimopolous et al, N Engl J Med. 2016; 375(14):1319-31), IRRs occurred in 45% and 48% of patients, respectively. Of these, 98% and 96%, respectively, occurred during the first infusion. Grade 3 IRRs occurred in 5.3% and 8.6% of patients in CASTOR and POLLUX, respectively. No grade 4 IRRs were observed in either trial. Standard of care includes extended infusion times for the first, second, and subsequent infusions with a three-drug pre-infusion prophylaxis strategy including diphenhydramine, dexamethasone or methylprednisolone, and acetaminophen with slow prolonged infusion times is recommended(Bhatnagar et al, Oncologist. 2017; 22:1347-53). A single-arm safety study of accelerated infusion rate indicate that administering daratumumab using a time-saving 90-minute infusion protocol can be safe. Of 28 patients treated with accelerated daratumumab infusion during their third and subsequent infusions, no IRRs were observed, and there was only one mild reaction with no further reactions during subsequent infusions at the 90-minute rate (Barr et al, Leukemia. Mar. 2018). Subsequently, a similar protocol for all daratumumab infusions was implemented at The Johns Hopkins Health System including five premedications and three medications (5+3) during the first two infusions. Premedication can be eliminated for lack of tolerance. The purpose of this study is to evaluate the safety and success of rapid daratumumab administration in clinical practice based on infusion times, IRRs prophylaxis medication administration, IRRs frequency, and management of IRRs in the ambulatory setting of the Johns Hopkins Health System, pre- and post-implementation of the 90-minute infusion protocol using a more robust premedication regimen (5+3) than previously published. Study Design and Methods: This study is approved by the institutional review board at The Johns Hopkins Hospital (IRB 00195519). This is a retrospective, chart review of daratumumab infusions prior to implementing the accelerated infusion rate. The inclusion criterion was adult patients who received daratumumab infusion in the ambulatory infusion clinic July 1, 2016 to May 25, 2018 for pre-implementation and July 1 2018 to June 30 2019 for the post-implementation period. Patients who only received inpatient administration of daratumumab were excluded due to limited infusion related documentation. The primary endpoint is the proportion of patients who experienced IRRs after daratumumab infusion. Secondary endpoints include proportion of patients with grade 1/2 or grade 3/4 IRRs, infusion duration (hours), and the number of pre and post infusion prophylaxis medications given. Other data collected will include but not limited to demographics, prior history of anaphylaxis, eczema, asthma, or other drug allergies to identify risk factors not previously defined. Results: Data collection and analysis are ongoing. The sample size for pre-implementation of rapid infusion is ninety-three patients. Documented IRRs occurred in 18 (19%) patients. The mean infusion time was 7.4 hours for first infusions (n=70), 8 hours for patients with IRRs in the first infusion (n=18) and 7.1 hours for patients without IRRs in the first infusion (n=52). The mean number of IRR prophylaxis medications given was 7.8 (range 2-9) for first or second infusions. All IRRs documented were grade 1 or 2. Additional data analysis will include descriptive statistics as well as comparison of infusion duration, and will use paired t-test within samples and student t-test across different samples. Final results will report safety of daratumumab rapid infusion in largest single center patient population to date. Disclosures Ali: Celgene: Research Funding; Poseida: Research Funding.
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Czuczman, Myron S., Marion Skipper, Alice Mohr, Zale P. Bernstein, Philip McCarthy, Francisco Hernandez-Ilizaliturri, and Asher Alban Chanan-Khan. "Phase I/II Study of Rituxan (R) in Combination with Doxil (D) in Patients (pts) with Relapsing or Refractory B-Cell Lymphoma: Promising Early Results." Blood 104, no. 11 (November 16, 2004): 1396. http://dx.doi.org/10.1182/blood.v104.11.1396.1396.
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Abstract In the past, the most common initial combination chemotherapy regimen used by most oncologists to treat B-cell lymphoma was the CHOP regimen. Although doxorubicin (DOX) is a major component of CHOP, it is associated with myelosuppression, alopecia, and potential cardiotoxicity. In vitro data has demonstrated synergistic activity between rituximab and certain drugs, including DOX. Because of D’s unique liposomal encapsulation, delivery, and toxicity profile, it may prove to be a more effective, less toxic anthracycline to combine with R. A formal Phase I/II trial to evaluate the safety and efficacy of R+D in pts with relapsing B-cell lymphoma was undertaken. R (375 mg/m2/dose) was given on day 1 and D (30 mg/m2/dose) on day 3 on q 21 day cycles for 6 cycles. Thirteen pts have completed therapy to date: 9F, 4M; Follicular lymphoma, grade 1 (n=6), grade 2 (n=1), grade 3 (n=3), DLBCL (n=3); med age = 63 (38–78); median number of prior Rx’s = 3 (range 1–8); prior anthracycline exposure (n=8). Overall, the combination of R + D was well-tolerated. Transient grade 3 cytopenias were noted in 3 pts with limited bone marrow reserve and grade 3 palmar/plantar erythrodysesthesia seen in 2 pts. All 13 pts completed the planned 6 courses of Rx. Objective responses were seen in 85% (11 of 13 pts), including 54% CR, 31% PR. Median time-to-progression has not been reached at 7+ months (range 4.5+ to 19+ months). No cardiac toxicity was seen and comparison of pre-Rx to post-Rx LVEF remained unchanged in 9, increased in 2, and decreased in 2 (yet still remaining > 50%). D + R immunochemotherapy is a well-tolerated, unique, non-cardiotoxic, and apparently effective salvage therapy for relapsed B-cell lymphoma. The study will continue until accrual of 42 pts has been reached.
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Bhattacharjee, Rimi, and Md Amit Hasan. "The activities of Bangladesh water development board on the social environment of Bhadrabila union, Narail sadar upazila, Bangladesh." Asian Journal of Medical and Biological Research 2, no. 2 (August 9, 2016): 297–303. http://dx.doi.org/10.3329/ajmbr.v2i2.29074.
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The study was conducted at Bhadrabila union, Narail sadar upazila, Narail in Bangladesh. The study period was carried out during September to December, 2013. In the selected areas, the study was conducted on 375 persons. The collected information was totally interview and observation based study. In the study area the highest age distribution was 50% in 21-40 years. The second highest was 39% for 41-60 years. The third highest was 7% for the year of 1-20. The lowest age distribution was for the year of 60 and above. This study found that the highest respondents of 39% are the member of 3-4 family member range. 32% respondents are in the member of 5-6 family member range. 12% respondents are in the member of 7-8 family member range. This study represent that 18% houses were kacha, 27% houses were tin shade 29% half building and 26% house were building. Almost 3% respondents were in class 1-3, 31% were in class 4-6, 46% were in between class 7-9, 10% in S.S.C level and left 9% were in above S.S.C level. Almost 79% had sanitary latrine. . It was found that 28% peoples were and poor their monthly income was 3,000-6,000 taka, 40% peoples were middle class their monthly income was 6,000-9,000 taka, about 24% peoples were rich their monthly income was 9,000-12,000 and lest 8% peoples income were 12,000+. 90% tube wells were arsenic free and only 10% tube wells are arsenic contaminated. About 77% were related with the BWDB and rests 13% were not the beneficiary of the BWDB. About 86% respondants were benifited by the activities of the BWDB. About 100% of respondents are fully satisfied by the activities of BWDB in arsenic test. It was shown that the social life of the respondents of Bhadrabila Union Parisad was getting better. The most important thing is almost 100% of the respondents were satisfied by the activities of BWDB.Asian J. Med. Biol. Res. June 2016, 2(2): 297-303
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Rahman, Md Mamunur, Debashis Kumar Mondal, Md Rurul Amin, and Mohammad Golam Muktadir. "Impact of stocking density on growth and production performance of monosex tilapia (Oreochromis niloticus) in ponds." Asian Journal of Medical and Biological Research 2, no. 3 (November 4, 2016): 471–76. http://dx.doi.org/10.3329/ajmbr.v2i3.30120.
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Stocking density is considered one of the important factors affecting fish growth. The study was aimed to compare the growth parameters of monosex tilapia at various stocking densities. The experiment was carried out during the period from 06 August to 22 December 2014. Three stocking densities were used as 125, 250 and 375 fish/dec and designated as treatment T1, T2 and T3 respectively each having two replicates. All the fishes were of same age group having average initial body weight of 1.34g. A commercial feed was supplied at the rate of 40% of the body weight and then gradually it was readjusted to 20%, 10%, 5% and 3% respectively and continued up to the end of the experiment. The water quality parameters were monitored at 14 days interval and the ranges were: temperature 19.34 to 31.40°C, pH 6.83 to 8.03, dissolved oxygen 4.78 to 6.82 mg/l and transparency 29.02 to 49.45cm.The result of the present study showed that the mean weight gain was significantly (P<0.01) highest in T1(120.58g) followed by T2(89.74g) and T3(74.58g).The average specific growth rates (SGR) was 2.590, 2.560 and 2.598 (%/day) in treatment T1, T2 and T3 respectively. There was significant (P<0.01) differences among the survival rate. The survival rate 87% was significantly highest in T1followed by 76% in T2 and 69% in T3.The fish productions were 13.25, 17.30 and 19.64 kg/decimal in T1, T2 and T3 respectively. Although the highest production was obtained in T3 but individually growth performance of monosex tilapia was highest in T1. The highest net profit was found (BDT 3,373.30) inT1compared toT2 (BDT 3,017) and T3 (BDT 2,918). The highest benefit cost ratio (BCR) was 1.79 in T1followed by 1.44 in T2and 1.28 in T3. Based on the result of present experiment, fish farmers might be suggested to rear tilapia at lower stocking density to get higher growth, survival and benefit in a short period of time.Asian J. Med. Biol. Res. September 2016, 2(3): 471-476
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Badacz, Rafał, Paweł Kleczyński, Jacek Legutko, Krzysztof Żmudka, Jacek Gacoń, Tadeusz Przewłocki, and Anna Kabłak-Ziembicka. "Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events." Biomedicines 9, no. 8 (August 20, 2021): 1055. http://dx.doi.org/10.3390/biomedicines9081055.
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Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001–1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26–3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22–6.12) and PAD (HR = 3.47, 95%CI = 1.88–6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000–1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01–1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001–1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).
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Uldrick, Thomas S., Mark N. Polizzotto, Armando Filie, Karen Aleman, Kathleen M. Wyvill, Richard F. Little, Seth M. Steinberg, et al. "Clinical, Immunologic, and Virologic Findings in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Lymphomas Suggest KSHV-Associated Inflammatory Syndromes Contribute to Symptoms and Disease Pathogenesis." Blood 120, no. 21 (November 16, 2012): 2708. http://dx.doi.org/10.1182/blood.v120.21.2708.2708.
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Abstract Abstract 2708 Background: KSHV, also known as human herpesvirus-8, is the etiologic agent of a lymphoproliferative disorder, KSHV-associated multicentric Castleman disease (KSHV-MCD), two lymphomas: primary effusion lymphoma (PEL) and large cell lymphoma arising in KSHV-MCD (together, KSHV-NHL) and Kaposi sarcoma (KS). KSHV-associated diseases mainly occur in patients with HIV. KSHV is notable for its modulation of host immune response, including induction of IL6 and IL10; and an IL6-related KSHV-associated inflammatory cytokine syndrome (KICS) has been described in HIV/KSHV infected patients without KSHV-MCD. The clinical features and natural history of KSHV-NHL are not well understood. We hypothesize KSHV-NHL is associated with pathophysiologic features similar to those of KSHV-MCD, and is unique among HIV-associated lymphomas. Methods: Clinical records of patients with KSHV-NHL diagnosed 2000-12, treated in the HIV and AIDS Malignancy Branch Clinic were reviewed, and evaluated for clinical, and laboratory abnormalities using our criteria for KICS (NCT01419561): at least 2 select clinical and laboratory manifestations, not otherwise explained; elevated c-reactive protein [CRP]; and KSHV viral load greater than 100 copies/106 PBMC; Additionally, serum inflammatory cytokines, (IFN-gamma, TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, IL12p70; Mesoscale Discovery, Gathersburg, MD) as well as PBMC-associated KSHV viral load, platelets, hemoglobin, and albumin were evaluated in KSHV-NHL patients, and compared to patients with A) Symptomatic KSHV-MCD and no KSHV-NHL, and B) Other HIV-associated lymphomas. Comparisons used exact two-tailed Wilcoxon rank sum tests, p<0.005 was considered statistically significant, p<0.05 strong trends. Results: Study cohort: 14 patients with HIV and KSHV-NHL; men (13), woman (1); median (med) age 42 yrs (26, 60); African American (4), African (2), Hispanic (4), white (4). Diagnoses included PEL (12, 5 with extracavitary manifestations) and large cell lymphoma in KSHV-MCD (2). Of the 14, 5 had pathologically confirmed KSHV-MCD, and 10 had cutaneous KS. Laboratory data: med CD4 126 cells/uL (15,1072), HIV viral load <100 copies/ml (7). All 10 KSHV-NHL with complete CRP and KSHV data either met criteria for KICS or had a history of KSHV-MCD; med CRP 48.8 g/dL (4.6, 114). Controls: A) KSHV-MCD (n=19): med age 43 (29, 54), med CD4 266 (67,1319). B) Other HIV-associated lymphoma (n=28): med age 37 (21, 60); med CD4 29 cells/uL (0, 730). Laboratory, immunologic, and virologic parameters were comparable between KSHV-NHL and KSHV-MCD, with no significant differences or trends towards differences in CRP, hemoglobin, platelets, CD4 count, albumin, sodium, KSHV viral load, or any measured cytokine. Compared to patients with other HIV-associated lymphomas, those with KSHV-NHL had statistically significant elevated serum IL10 (med 513 vs 12.2 pg/ml, p<0.0001), IL6 (29 vs 4.1 pg/dl, p=0.0011), KSHV viral load (med 3913 vs. 0 copies/106 PBMC, p<0.0001), and hypoalbuminemia (med 1.8 vs 3.5 mg/dL, p=0.001) (Figure). Strong trends towards statistically significant thrombocytopenia (med 87 vs 246 K/uL, p = 0.0064), anemia (med 8.9 vs 11.1 gm/dl, p=0.019), hyponatremia (med 134 vs 137 mEq/L, p=0.03), and elevated IL1beta (1.6 vs. 0.5 pg/dL, p=0.024), and IFNgamma (med 6 vs 2.9 pg/dl, p=0.038) were also observed. Conclusions: In the era of antiretroviral therapy, KSHV-NHL in HIV occurs at a broader range of CD4 counts than previously appreciated, often in the setting of suppressed HIV. Significant overlap exists between KSHV-associated lymphoproliferative disease and KSHV-NHL. Essentially all KSHV-NHL patients presented with inflammatory symptoms, elevated CRP, hypoalbuminemia, and cytopenias, and either had KSHV-MCD or met our working criteria for KICS. Elevated KSHV-infected PBMCs and associated KSHV modulation of host immune response leading to marked elevations in IL10 and IL6 likely contribute to symptoms and KSHV-NHL pathogenesis. KSHV-MCD and KICS Natural History studies are ongoing, and evaluation of curative-intent regimens for KSHV-NHL incorporating strategies to target these unique immunologic and virologic abnormalities is warranted. Disclosures: No relevant conflicts of interest to declare.
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Faruque, Shakila, AKFH Bhuiyan, Md Yousuf Ali, MSK Sarker, and Ziaul Faruque Joy. "Breeding for the improvement of indigenous chickens in Bangladesh: performance of second generation." Asian Journal of Medical and Biological Research 3, no. 1 (April 14, 2017): 66–71. http://dx.doi.org/10.3329/ajmbr.v3i1.32038.
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The improvement of productivity of indigenous chicken is a long desire in the country. Present research is a part of the long-term selection program being undertaken to evaluate the carcass characteristics and expected response to selection of second generation (G2) of indigenous chicken under intensive management in Bangladesh. A total of 1643-day-old chicks comprising of 3 types of chicken namely Naked Neck (NN), Hilly (H) and Non-descript Desi (ND) were hatched in a two batches for this study. In second generation (G2), selection was practiced at 3 (three) stages of birds life, firstly and secondly at 8 and at 16 weeks of age, selection was performed on the basis of breeding value for 8 and 16 week body weight. Thirdly, at 40-week of age, on the basis of an index comprising the parameters of age at sexual maturity (ASM), body weight (BW), egg production (EP) and egg weight (EW). Improvement target of egg weight was to increase by 1g and improvement target of egg production rate was to increase by 2 % per generation. The main target was the mean body weight in H, ND and NN chicken has to be gone up from the initial eight-week body weight of 375, 342 and 331g to 500 g at eight weeks of age. At 8, 10 and 12 weeks of age, six birds from each genotype were slaughtered to analyze the meat yield traits. Slaughter data were analyzed in a 3(genotype)×3(slaughter age) factorial arrangement in CRD by General Linear Model (GLM) Univariate Procedure in SPSS Computer Program. Genotype and slaughter age had significant effect (p<0.001) on dressing percentage. Body weight at 8 weeks of age was expected to improve by 51.21 vs. 24.03; 37.74 vs. 15.47 and 26.26 vs. 9.65g; respectively for ND, H and NN males and females. In terms of body weight H genotype was superior and NN genotype was for dressing percentage. As a result of selection; EP, BW increased and ASM reduced in second generation than that of the foundation stock.Asian J. Med. Biol. Res. March 2017, 3(1): 66-71
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Dodokhova, Margarita Avdeevna, Inga Movlievna Kotieva, Dmitriy Borisovich Shpakovsky, Andrej Vladimirovich Safronenko, Ekaterina Fedorovna Komarova, Margarita Stefanovna Alkhuseyn-Kulyaginova, Elena Rudolfovna Milaeva, and Alexander Albertovich Shtil. "Antimetastatic effect of organotin compounds on the model of melanoma B16 in the experiment." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e21564-e21564. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e21564.
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e21564 Background: Melanoma is an extremely malignant tumor. The unfavorable prognosis in the treatment of patients is mainly due to aggressive metastasis of the tumor in various ways: hematogenic, lymphogenic and lymphohematogenic. Metastatic melanoma cells are relatively drug - resistant. Despite some successes in the treatment of melanoma, the search for new antimetastatic substances remains an urgent task of experimental pharmacology and oncology. Organotin compounds were studied by us as promising candidates for antimetastatic agents. Methods: The study was conducted on experimental C57BL/6 mice (n =72, each cohort contained 12 mice) with B16 melanoma (subcutaneous transplantation) to determine the intensity of metastasis in the presence of the cytotoxic organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) [1-3] (Me3). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Female mice (8 weeks of age, weighing 21-22 g) were administered intraperitoneal 1% aqueous gelatin solution of organotin Me3 daily for 5 days. The total doses in the first series of the experiment were 150, 250, 375 mg/kg (I, II, III cohorts and IV control group), which allowed us to choose the most effective dose of Me3. After that, in the second series of experiments, the metastasis inhibition index was evaluated in group V (total dose 375 mg/kg) and control group VI. The animals were euthanized on the 18th day after the tumor was inoculated. Results: It was shown that when administered intraperitoneal to mice, Me3 did not inhibit the growth of B16 melanoma in any of the groups. The results showed that the average life expectancy of animals in the experimental group III with the introduction of Me3 at a dose of 375 mg/kg significantly increased and amounted to 30.1±2.5 days, in control mice of group IV-21.8±2.6 days. In the second series of the experiment, after 18 days, the index of metastasis inhibition was almost twice lower (54%) in group V than in the control group (VI). Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) (Me3) is an effective antimetastatic agent in transplanted experimental mouse melanoma B16 at a total dose of 375 mg/kg.
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Ramaswami, Ramya, Kathryn Lurain, Vickie Marshall, Nazzarena Labo, Anaida Widell, Matthew Lindsley, Mark N. Polizzotto, Denise Whitby, Thomas S. Uldrick, and Robert Yarchoan. "IL-13 Expression Characterizes Effusions Associated with Primary Effusion Lymphoma but Not Other Disorders Caused By Kaposi Sarcoma Herpesvirus (KSHV)." Blood 132, Supplement 1 (November 29, 2018): 4137. http://dx.doi.org/10.1182/blood-2018-99-117668.
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Abstract BACKGROUND: Kaposi sarcoma herpesvirus (KSHV, also called human herpesvirus-8) is the causative agent of 3 disorders: primary effusion lymphoma (PEL), Kaposi sarcoma (KS), and a plasmablastic form of multicentric Castleman disease (KSHV-MCD). It also causes KSHV inflammatory cytokine syndrome (KICS), which is characterized by inflammatory symptoms and an elevated KSHV viral load. Multiple KSHV-associated diseases, which usually develop in HIV-infected patients, can present together in the same patient. Effusions can occur in each of these diseases, thereby presenting a diagnostic challenge. Identifying PEL is especially crucial as prompt treatment with multi-agent chemotherapy can be curative. We analyzed effusions from patients with KICS, PEL, and KSHV-MCD to identify distinct immunologic characteristics and virologic profiles that may aid diagnosis, inform treatment and elucidate pathogenesis. PATIENTS AND METHODS: We identified 22 HIV-infected patients with effusions [pleural effusions (20), ascites (1) and pericardial effusion (1)] with diagnoses of PEL (9 patients), KICS (8 patients), or KSHV-MCD (5 patients). All patients had a concurrent diagnosis of KS. We obtained clinical and immunologic characteristics from effusions and paired serum samples at the same timepoint for each patient. Serum and effusion cytokine levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, and IL-12p70; interferon gamma (IFN-g); tumor necrosis factor alpha (TNF-a); vascular endothelial growth factor (VEGF); and inducible protein 10 (IP-10) were evaluated using a commercial multiplex assay. Peripheral blood mononuclear cell (PBMC) and effusion- associated KSHV and Epstein Barr virus (EBV) viral DNA (KSHV-VL, EBV-VL) in PBMC and cells were quantified using PCR with primers to KSHV K6 and EBV pol. Effusion and serum immunologic and virologic characteristics were compared within each disease and separately between diseases using the Wilcoxon sign rank test and Wilcoxon rank sum test, respectively. In these exploratory analyses with few patients, no correction was made for multiple comparisons. RESULTS: In patients with PEL, the median (med) age was 42 years with med CD4+ count of 54 T-cells/μL and HIV viral load (VL) of 325 copies/mL. In those with KICS, the med age was 32 years, with a med CD4+ count of 119 T-cells/μL and HIV VL of 48 copies/mL. In patients with KSHV-MCD, the med age was 31 years, med CD4+ count of 118 T-cells/μL and HIV VL was 75 copies/mL. IL-13 was substantially higher in PEL effusions as compared to serum levels (med 16.9 vs. <0.12 ng/ml; p=0.007). In addition, patients with PEL had significantly higher levels of 6 other cytokines (IL-12p70, IL-1ß, IL-2, IL-4, IL-6 and IP-10) in effusions as compared with serum (Table 1, p<0.05). In both KSHV-MCD and KICS, IL-12p70, IL-2 and IL-4 levels were higher in the effusion as compared with serum (p<0.05). In analyses comparing serum and cytokine differences among diseases, effusions from patients with PEL had detectable levels of IL-13 (med 16.9 ng/ml; interquartile range 9.7-26.9 ng/ml) compared to patients with KSHV-MCD (med <0.114 ng/ml; p=0.0037) or KICS (med <0.114 ng/ml; p=0.0003). PEL effusions had higher IL-1ß levels as compared with KICS effusions (p=0.0028). Serum IL-10 levels were also higher in PEL as compared with KICS (med 51.6 vs. 2.5ng/mL; p=0.0015). KSHV VL levels were significantly higher in PEL effusions as compared to KICS effusions (med 31,428,571 vs. 569 copies/mL; p=0.0005) and KSHV-MCD (med 231,884 copies/mL; p=0.02). CONCLUSIONS: In HIV-infected patients, effusions can indicate a diagnosis of PEL, KSHV-MCD and/or KICS. Quantifying KSHV VL in the effusion may be useful in the diagnosis of PEL. Effusions in PEL had a distinct profile compared to the circulation or other KSHV-associated diseases, particularly with regard to elevated IL-13, which may aid in diagnosis. In contrast, the inflammatory and virologic findings in KSHV-MCD and KICS effusions roughly paralleled the levels seen in the circulation. This study suggests that KSHV upregulation of IL-13 is a unique feature of PEL, which may contribute to PEL pathogenesis through STAT6 activation and be a potential future therapeutic target. Disclosures Uldrick: Celgene: Patents & Royalties: 10,001,483 B2; Celgene: Research Funding; Merck: Research Funding. Yarchoan:Celgene Corp.: Research Funding; NIH: Patents & Royalties: Patents on IL-12 for KS and cereblon-binding drugs for KSHV diseases. Spouse has patent on KSHV IL-6. Patents assigned to DHHS/NIH..
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Arai, Sally, B. Sahaf, C. Jones, James Zehnder, Robert Lowsky, S. Strober, Judith Shizuru, et al. "Rituximab Infusion Two Months after Nonmyeloablative Transplantation Maintains B-Cell Disease Control with Minimal GVHD." Blood 108, no. 11 (November 16, 2006): 2907. http://dx.doi.org/10.1182/blood.v108.11.2907.2907.
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Abstract B cells are implicated in the pathophysiology of chronic GVHD, as evidenced by the association of Ab production against minor histocompatibility Ags with chronic GVHD, and rituximab efficacy in chronic GVHD. We hypothesize that anti-B cell therapy beginning 56 days after nonmyeloablative total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) transplantation reduces chronic GVHD. Cognizant of possible GVL loss with B cell depletion, we treated patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) because any loss of GVL may be offset by rituximab’s direct anti-B cell tumor efficacy. Patients were conditioned with TLI (80 cGy in 10 fractions, d-11 to d-1) and ATG (1.5mg/kg/day, d-11 to d-7, total 7.5mg/kg). PBSC were infused on day 0. Primary GVHD prophylaxis was MMF from day 0 until d28 for MRD, d100 for URD and cyclosporine (CSA) tapered off by 6 months. To diminish donor B cell alloimmunity, rituximab (375 mg/m2) was infused on days 56, 63, 70, and 77 post-transplant. Fourteen patients have received HCT, and 11 (median age 57, range 46–65 yrs) have received four rituximab infusions (5 fludarabine-refractory, unmutated immunoglobulin heavy-chain variable region gene (IgVH) CLL; 6 MCL). Median follow-up is 290 days (108–381 days). No infusion related toxicities occurred. Transient leukopenia in all patients and frank neutropenia in one patient was noted as early as 30 days post-rituximab. There was one graft loss at day 50 in a patient with MCL progression. Only 3/11 patients had peripheral blood CD3 donor chimerism >95% before rituximab infusion day 56, but 6/7 patients achieved full donor chimerism post-rituximab day 180, showing rituximab has no detrimental effect on engraftment. Peripheral blood CD19+ B cells were undetectable in all patients days 90–270, and 2/2 evaluable patients at one year now have CD27+ CD19+ donor B cell reconstitution. Infections post-transplant include early CMV reactivation (5), influenza B (1), aspergillus sinusitis (1), ecthyma gangrenosum (1), VZV (1). All infections resolved. Non-relapse mortality at 100 days and currently is 0%. Four of the 5 unmutated IgVH CLL patients with diffuse lymphadenopathy and marrow involvement by 4-color flow and IgVH quantitation prior to HCT have achieved molecular CR by IgVH PCR. One CLL patient progressed 9 months after HCT and has received DLI. Four MCL patients were transplanted in PR; one achieved CR, 3 progressed before rituximab infusion and 2 subsequently died. The third progressed MCL patient responded to salvage chemotherapy with development of chronic GVHD and achieved CR. No patients developed acute GVHD. One patient developed chronic GI GVHD that resolved with six weeks of steroids. Rituximab infused 56–77 days after TLI-ATG is well tolerated and able to modulate donor B cell reconstitution without detrimental effect on engraftment or infection incidence. No acute GVHD occurred. This novel approach of rituximab infusion two months after TLI-ATG HCT provides safe in vivo peripheral donor B cell depletion with low chronic GVHD incidence thus far. Importantly, GVL is maintained with four CLL and two MCL patients achieving molecular CR after HCT. CLL/MCL Med Age Med f/u MRD/URD GVHD CD3>95% Donor Chimerism Disease status pre-HCT»last f/u 5/6 57 yrs 290 days 9/2 aGVHD- none cGVHD- one,d257 D56 pre-rituximab: 3/11 pts>95%; D180: 6/7 pts>95% CLL: 4 PR»CR; 1PR»PD--DLI; MCL: 1PR»CR; 3PR»PD-2 deaths; 2CR»CR
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Bahlis, Nizar, Meletios A. Dimopoulos, Darrell J. White, Lotfi Benboubker, Gordon Cook, Merav Leiba, P. Joy Ho, et al. "Three-Year Follow up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM)." Blood 132, Supplement 1 (November 29, 2018): 1996. http://dx.doi.org/10.1182/blood-2018-99-112697.
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Abstract Introduction: Daratumumab is a human, CD38-targeted, IgGκ monoclonal antibody with both direct on-tumor and immunomodulatory mechanisms of action. In the phase 3 POLLUX study, D-Rd reduced the risk of disease progression or death by 63% and significantly increased the overall response rate (ORR) versus Rd alone (93% vs 76%; P <0.001) in RRMM patients (pts). When combined with standard of care regimens across three phase 3 studies including POLLUX, daratumumab demonstrated ≥50% reductions in the risk of progression or death, doubled complete response (CR) rates, and tripled minimal residual disease (MRD)-negative rates at the 10-5 sensitivity threshold in pts with RRMM or newly diagnosed MM (Palumbo A, et al. N Engl J Med 2016. 375[8]:754-766; Dimopoulos MA, et al. N Engl J Med 2016. 375[14]:1319-1331; Mateos MV, et al. N Engl J Med 2018. 378[6]:518-528). Improvements in deeper responses gained from novel MM treatments have led to interest in sustained MRD negativity as a potential surrogate endpoint (Kumar S, et al. Lancet Oncol 2016. 17[8]:e328-e346; Anderson KC. Blood Adv 2017. 1[8]:517-521). Here, we present updated efficacy and safety analyses of POLLUX, including sustained MRD negativity, after >3 years of median follow-up. Methods: Pts with ≥1 prior line of therapy were randomized (1:1) to receive Rd (lenalidomide 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone 40 mg per week) ± daratumumab (16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, then Q4W until disease progression). High risk cytogenetic abnormalities included t(4;14), t(14;16), and del17p. At the time of suspected CR and at 3 and 6 months after confirmed CR (and every 12 months thereafter if CR was maintained), bone marrow aspirates were assessed for MRD using clonoSEQ® V2.0 (Adaptive Biotechnologies, Seattle, WA). Sustained MRD negativity was defined as maintenance of MRD negativity at the 10-5 threshold for ≥6 or ≥12 months. PFS on subsequent line of therapy (PFS2), an exploratory endpoint, was defined as time from randomization to progression after next line of subsequent therapy or death. Results: A total of 569 pts were randomized (D-Rd, n = 286; Rd, n = 283). At a median follow-up of 39.5 months, D-Rd significantly prolonged progression-free survival (PFS) versus Rd (median, not reached [NR] vs 17.5 months; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.35-0.55; P <0.0001); 36-month PFS rate was 55% versus 28%. D-Rd also prolonged PFS versus Rd among pts with 1 prior line of therapy and pts with 1-3 prior lines of therapy (Table 1). A PFS benefit for D-Rd versus Rd was also observed regardless of cytogenetic risk status (Table 1). D-Rd was associated with a significantly higher ORR versus Rd (93% vs 76%), including higher rates of ≥very good partial response (80% vs 49%) and ≥CR (56% vs 23%; all P <0.0001). At the 10-5 sensitivity threshold, MRD-negativity was achieved by 87 (30%) D-Rd pts versus 15 (5%) Rd pts (P <0.000001). Among the ITT population, sustained MRD negativity was achieved by 47 (16%) D-Rd pts versus 2 (0.7%) Rd pts for ≥6 months and 37 (13%) D-Rd pts versus 1 (0.4%) Rd pt for ≥12 months (both P <0.0001). Median time to next therapy for D-Rd versus Rd was NR in the D-Rd group versus 22.8 months in the Rd group (HR, 0.38; 95% CI, 0.29-0.49; P <0.0001). In the D-Rd group, 98 (34%) overall survival (OS) events were observed versus 118 (42%) OS events in the Rd group; OS follow-up is ongoing. The median duration of treatment was 34.3 months in the D-Rd arm versus 16.0 months in the Rd arm. The most common (≥10%) grade 3/4 treatment-emergent adverse events (TEAEs) observed with D-Rd versus Rd are described in Table 2. No differences were observed for D-Rd versus Rd in discontinuations due to TEAEs (14% of pts in each treatment group) or incidences of second primary malignancies (7% of pts in each treatment group). Updated data including PFS2 will be presented at the meeting. Conclusion: After >3 years of median follow-up, D-Rd continued to demonstrate a significant PFS benefit and higher rates of deeper responses versus Rd alone in RRMM pts. The higher rate of sustained MRD negativity with D-Rd compared with Rd suggests that continued D-Rd treatment drives these deep responses and delays progression. No new safety signals were observed following a median of 34 months of D-Rd exposure. Disclosures Bahlis: Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Dimopoulos:Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. White:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cook:Amgen, Bristol-Myers Squibb, GlycoMimetics, Celgene, Janssen and Takeda and Sanofi: Honoraria; Celgene, Janssen and Takeda: Research Funding. Ho:Takeda: Honoraria, Other: Travel to meeting; Novartis: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Other: Travel to meeting. Moreau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Krevvata:Janssen Research & Development, LLC: Employment. Chiu:Janssen Research & Development, LLC: Employment. Qin:Janssen Research & Development, LLC: Employment. Okonkwo:Janssen Research & Development, LLC: Employment. Trivedi:Janssen Research & Development, LLC: Employment. Qi:Janssen Research & Development, LLC: Employment. San-Miguel:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Roche: Honoraria.
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Avet-Loiseau, Hervé, Jianming He, Katharine S. Gries, Huiling Pei, Sourish Saha, Christopher Chiu, Sarah Cote, and Annette Lam. "The Relationship between Minimal Residual Disease and Patient Reported Outcomes in Relapsed/Refractory Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 3273. http://dx.doi.org/10.1182/blood-2018-99-113571.
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Abstract Objective With the introduction of novel treatments for multiple myeloma, patients are now achieving deeper and sustainable clinical responses. Recent studies have demonstrated that achieving Minimal Residual Disease (MRD) negativity leads to better progression-free survival and overall survival outcomes (Lahuerta JJ, et al. J Clin Oncol 2017. 35[25]:2900-10; Munshi NC, et al. JAMA Oncol 2016. 3[1]:28-35; Landgren O, et al. Bone Marrow Transplant 2016. 51[12]:1565-1568). However, the relationship between MRD status and patient reported outcomes (PRO) has not been reported. The objective of this analysis is to evaluate whether PRO endpoints change by MRD status using data from two randomized clinical trials of daratumumab containing treatment regimens, POLLUX (Dimopoulos MA, et al. N Engl J Med 2016. 375[14]:1319-1331) and CASTOR (Palumbo A, et al. N Engl J Med 2016. 375[8]:754-766), for patients with relapsed or refractory multiple myeloma. Methods MRD status was assessed in POLLUX at the time of suspected CR, and at 3 and 6 months post-suspected CR for responders. Similarly, in CASTOR, MRD status was assessed for patients at the time of suspected CR and at 6 months and 12 months after first dose. MRD was assessed via next generation sequencing using the clonoSEQ® assay V2.0 (Adaptive Biotechnologies, Seattle, WA) at sensitivities of 0.001%. The PRO instruments (EORTC-QLQ-C30 and EQ-5D-5L) were collected in both POLLUX and CASTOR study prior to treatment, during the treatment phase, and post-progression. EQ-5D-5L assessed general health status and included an index value and visual analog scale (VAS) score. EORTC QLQ C30 assessed health related quality of life and included five functional scales (physical, role, emotional, social and cognitive), three symptom scales (fatigue, nausea & vomiting and pain) and a global health status (GHS) scale as well as six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Summary statistics (mean, standard deviation, median, min and max) by MRD status (baseline, prior to MRD negativity, MRD negativity prior to progression) were reported and for subjects who did not achieve MRD negativity (baseline, post baseline prior to progression) on a pooled sample of subjects from the two clinical trials. To interpret a meaningful change, a 5-point threshold was defined based on the EORTC guidelines for assessing quality of life in clinical trials. Results Overall 137 subjects in both CASTOR and POLLUX achieved MRD negativity and had PRO data available for analysis. At baseline, GHS, EQ-5D-5L VAS and index value were 62.1, 66.7, and 0.72 respectively (GHS and VAS scores closer to 100, and index value closer to 1.0 represent better health state). Mean values increased to 67.2, 70.9, and 0.75 after achieving MRD negativity. Pain scale (symptom scores closer to 0 represent less symptoms) reduced from 30.4 to 23.5 and fatigue was similar (33.8 at baseline to 31.2) when patients achieved MRD negativity. However, when we compared the five functional scales prior to and post MRD negativity, no evident differences were identified. The mean change from baseline to post-MRD-negativity in the EORTC QLQ-C30 GHS and Pain scores exceeded a 5-point threshold, reflecting a meaningful change in subject's health-related quality of life. A total of 893 subjects in the pooled data set did not achieve MRD negativity and had PRO data available for analysis (EQ-5D-5L data were not available for 3 subjects). Baseline values for these MRD positive subjects were 60.0, 65.3, and 0.71 and the mean post-baseline (pre-progression) values remained similar at 61.1, 66.0, and 0.71 for GHS, VAS, and the index value, respectively. Pain reduced from mean 33.3 to 29.4 and fatigue was similar, changing from 36.2 to 37.6. Conclusion To our knowledge, this is the first analysis exploring the relationship between MRD status and PRO endpoints. Results from this analysis demonstrate that patients who achieve MRD negativity status show a trend in better health-related quality of life, with meaningful improvement in EORTC QLQ-C30 GHS and pain scores. These preliminary findings indicate that overall health-related quality of life and symptom domains of EORTC-QLQ-C30 and EQ-5D-5L might be sensitive to changes in MRD status, with changes in GHS and Pain exceeding meaningful threshold for subjects. Disclosures Avet-Loiseau: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. He:Janssen global services: Employment. Gries:Janssen Research & Development, LLC: Employment. Pei:Janssen Research & Development, LLC: Employment. Saha:Janssen Research & Development, LLC: Employment. Chiu:Janssen Research & Development, LLC: Employment. Cote:Janssen Research & Development, LLC: Employment. Lam:Janssen Global Services, LLC: Employment.
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Zamora-Ros, Raul, Viktoria Knaze, Leila Luján-Barroso, Isabelle Romieu, Augustin Scalbert, Nadia Slimani, Anette Hjartåker, et al. "Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study." British Journal of Nutrition 109, no. 8 (September 14, 2012): 1498–507. http://dx.doi.org/10.1017/s0007114512003273.
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A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35 628 subjects, aged 35–74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2 %) and flavan-3-ol monomers (24·9 %) and the principal food sources were tea (25·7 %) and fruits (32·8 %). In the MED region, proanthocyanidins (59·0 %) were by far the most abundant contributor and fruits (55·1 %), wines (16·7 %) and tea (6·8 %) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.
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Frazer, J. Kimble, Stanton Goldman, Lynette Smith, Lauren Harrison, Sherrie L. Perkins, and Mitchell S. Cairo. "Efficacy of rituximab plus FAB group C chemotherapy without CNS radiation in CNS-positive pediatric Burkitt lymphoma/leukemia: A report from the Children’s Oncology Group." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 9501. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.9501.
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9501 Background: Historically, CNS-positive (CNS+) mature B-NHL in children and adolescents has been associated with a dismal outcome (Miles/Cairo, Br J Haematol, 2012). Adding CNS radiation and high-dose MTX and cytarabine to group C therapy for children with CNS+ B-NHL yielded a 77% 5-yr EFS in LMB89 (Patte et al., Blood, 2001). An ensuing FAB/LMB96 trial replaced cranial radiation with further HD-MTX and intrathecal therapy with similar results (75% 4-yr EFS) (Cairo et al., Blood, 2007). Here, patients with marrow and CNS+ disease fared worse than isolated CNS+ (61% vs. 83% 4-yr EFS, p<0.001), with >50% of CNS+ patients who progressed or recurred having systemic, but not CNS, relapse. Rituximab, a chimeric anti-CD20 antibody, improved EFS, PFS, and OS when added to chemotherapy for adults with DLBCL (Coiffier et al., N Engl J Med, 2002; Pfreundschuh et al., Lancet Oncol, 2006). We tested whether adding rituximab to FAB group C chemotherapy in pediatric patients with CNS+ B-NHL was safe and efficacious. Methods: Children and adolescents (<21 yrs.) with CNS+ B-NHL received FAB group C1 therapy (Cairo et al., Blood, 2007). Rituximab (375 mg/m2/dose) was given twice in COPADM courses 1 & 2 and once in CYVE courses (Cairo et al., ASCO, 2010). CSF blasts (>1), cranial nerve palsy (CNP), intra-cerebral mass (ICM), and/or parameningeal extension (PME) defined cases as CNS+. Results: Of 40 eligible Group C patients,15 (38%) were CNS+; all 15 had Burkitt morphology. Eight CNS+ patients were CSF+ [WBC median 35 (range 1-1104)] with 6 cases CNP+, 4 PME+, and 1 ICM+. No adverse events were attributed to rituximab. Fourteen of 15 CNS+ patients (93%) are alive and disease-free. Of 7 BM-/CNS+ patients, 100% are NED. In BM+/CNS+ cases, 7/8 (88%) are NED, with one patient progressing with systemic and CNS disease. Conclusions: Addition of rituximab to group C FAB therapy was well tolerated. Outcomes in this small cohort of 15 children and adolescents with CNS+ BL (93%) suggest that adding rituximab to FAB group C therapy without CNS radiation may reduce systemic relapse. Large randomized studies are warranted to test this hypothesis in this previously high-risk clinical subgroup.
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Lobo Prat, D., I. Castellví, D. Castillo, S. Orozco, A. Mariscal, L. Martínez-Martínez, A. M. Millán Arciniegas, et al. "AB0666 PROGNOSTIC VALUE OF SERUM KREBS VON DEN LUNGEN-6 GLYCOPROTEIN CIRCULATING LEVELS IN COVID-19 PNEUMONIA: A PROSPECTIVE COHORT STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1365.1–1365. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1359.
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Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; p<0.02).Conclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.
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Author, No. "March Of Medicine." Journal of Nepal Medical Association 2, no. 1 (January 1, 2003): 51–55. http://dx.doi.org/10.31729/jnma.900.
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Pseudotumor cerebri and corticosteroid therapy. A.E. Walker, M.D., and J.J. Adamkiewicz, M.D. Baltimore. J.A.M.A. 188: 9 (June 1, 1964) 779.Tetracycline in the Treatment of Cholera.W.B. Greenough, M D , R S Gordon. Jr.,M.D., T.S. Rosenberg. M.D..B.T. Davies, M.D. THE LANCET 1 : 7329 (Feb. 15, 1964)355.Medical Radiations and Leukaemia : a Retrospective Survey. F.W. Gunz and H.R. Atkinson.Brit.Med.Jou. (Feb. 15,1964) 389.Radiology in Diagnosis of Coeliac Disease. W. Morrice McCrae and Elizadeth M.Sweet. Brit.Med.Jou. (July 18,1964) 163.Long-term Administration of Corn Oil in Management of Patients after Myocardial Infarction : A Four-year Study. W.C. Watson, M B., M.R.C.P., M.R.C.P. Glasg. Brit. Med. Jou. (Nov. 30,1963) 1366.Evidence for "Rebound" Hypercoagulability After Stopping Anticoagulants. L.Poller,M.D.,J.Thomson, A.I.M.L.T. THE LANCET 2:7350 (July 11, 1964) 62.Ampicillin in Treatment of Salmonella typhi Carriers. J.M.F. Whitby, L.M.S.S.A. THE LANCET 2 : 7350 (July 11, 1964) 71.Comparison of Ampicillin and Chloramphenicol in Treatment of Paratyphoid Fever. R.A. Sieet, G.Sangster, and J. McC. Murdooh. Brit.Med.Jou.(Jan.18,1961) 148.Effect of Nicotinic Acid on Abnormal Serum Lipids. O.Fitzgerald, A. Heffernan, P. Brennan, R. Mulcahy, J.J. Fennelly, and R. Mulcahy, J.J. Fennelly, and R. McFarlane-Brit.Med.Jou. (Jan. 18, 1964) 157.
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Ibidhi, Ridha, and Sergio Calsamiglia. "Carbon Footprint Assessment of Spanish Dairy Cattle Farms: Effectiveness of Dietary and Farm Management Practices as a Mitigation Strategy." Animals 10, no. 11 (November 10, 2020): 2083. http://dx.doi.org/10.3390/ani10112083.
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Greenhouse gas emissions and the carbon footprint (CF) were estimated in twelve Spanish dairy farms selected from three regions (Mediterranean, MED; Cantabric, CAN; and Central, CEN) using a partial life cycle assessment through the Integrated Farm System Model (IFSM). The functional unit was 1 kg of energy corrected milk (ECM). Methane emissions accounted for the largest contribution to the total greenhouse gas (GHG) emissions. The average CF (kg CO2-eq/kg of ECM) was 0.84, being the highest in MED (0.98), intermediate in CEN (0.84), and the lowest in CAN (0.67). Two extreme farms were selected for further simulations: one with the highest non-enteric methane (MED1), and another with the highest enteric methane (CAN2). Changes in management scenarios (increase milk production, change manure collection systems, change manure-type storage method, change bedding type and installation of an anaerobic digester) in MED1 were evaluated with the IFSM model. Changes in feeding strategies (reduce the forage: concentrate ratio, improve forage quality, use of ionophores) in CAN2 were evaluated with the Cornell Net Carbohydrate and Protein System model. Results indicate that changes in management (up to 27.5% reduction) were more efficient than changes in dietary practices (up to 3.5% reduction) in reducing the carbon footprint.
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Xiang, Rui, Min Feng, Xin Zhou, Lihong Ma, and Ningfei Dong. "circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p." Open Medicine 16, no. 1 (January 1, 2021): 338–50. http://dx.doi.org/10.1515/med-2021-0229.
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Abstract Background Colorectal cancer (CRC) is one of the deadliest cancers in the world. Increasing evidence suggests that circular RNAs (circRNAs) are implicated in CRC pathogenesis. This study aimed to determine the role of circAPLP2 and explore a potential mechanism of circAPLP2 action in CRC. Methods The expression of circAPLP2, miR-335-5p and helicase lymphoid-specific (HELLS) mRNA in CRC tissues and cells was measured by quantitative real-time polymerase chain reaction (qPCR). The functional effects of circAPLP2 on cell cycle progression/cell apoptosis, colony formation, cell migration, invasion and glycolysis metabolism were investigated by flow cytometry assay, colony formation assay, wound healing assay, transwell assay and glycolysis stress test. Glycolysis metabolism was also assessed by the levels of glucose uptake and lactate production. The protein levels of HELLS and HK2 were detected by western blot. The interaction between circAPLP2 and miR-335-5p, or miR-335-5p and HELLS was verified by dual-luciferase reporter assay. The role of circAPLP2 on solid tumor growth in nude mice was investigated. Results circAPLP2 and HELLS were overexpressed, but miR-335-5p was downregulated in CRC tissues and cells. Functional analyses showed that circAPLP2 knockdown suppressed CRC cell cycle progression, colony formation, migration, invasion and glycolysis metabolism, induced cell apoptosis and blocked solid tumor growth in nude mice. Moreover, miR-335-5p was a target of circAPLP2, and miR-335-5p could also bind to HELLS. Rescue experiments presented that miR-335-5p inhibition reversed the effects of circAPLP2 knockdown, and HELLS overexpression abolished the role of miR-335-5p restoration. Importantly, circAPLP2 could positively regulate HELLS expression by mediating miR-335-5p. Conclusion circAPLP2 triggered CRC malignant development by increasing HELLS expression via targeting miR-335-5p, which might be a novel strategy to understand and treat CRC.
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Jeep, John M. "Althochdeutsches Wörterbuch. Auf Grund der von Elias von Steinmeyer hinterlassenen Sammlungen im Auftrag der Sächsischen Akademie der Wissenschaften zu Leipzig. Begründet von Elisabeth Karg-Gasterstädt und Theodor Frings. Herausgegeben von Hans Ulrich Schmid unter der Leitung von Brigitte Bulitta. Bearbeitet von Brigitte Bulitta, Frank Heidermanns, Aletta Leipold, Almut Mikeleitis-Winter, Susanne Näßl, Katja Schmidt, Ulrike Seeger, Torsten Woitkowitz unter Mitarbeit von Christina Waldvogel. Band VII: O–R. Dreizehntente Lieferung. Berlin und Boston: Walter de Gruyter Akademie Forschung, 2018, Sp. 958–1036." Mediaevistik 32, no. 1 (January 1, 2020): 353. http://dx.doi.org/10.3726/med.2019.01.60.
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In gewohnt zügiger Folge (zu den letzten sechs Lieferungen siehe die Rezension Mediaevistik 31: 345–346) erscheint nun die 13. Lieferungen des 7. Bandes des Althochdeutschen Wörterbuchs, ,,rîhhen1“–,,ringan“.
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Siddiqui, Aisha. "Acute Coronary Syndrome in Diabetics Admitted in King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia." Journal of King Abdulaziz University-Medical Sciences 15, no. 3 (2008): 61–70. http://dx.doi.org/10.4197/med.15-3.5.
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Al-Ansari, Soliman. "Virulence Factors of Pseudomonas aeruginosa after Postantibiotic Effects Induced by Different Antimicrobial Agents." Journal of King Abdulaziz University-Medical Sciences 16, no. 3 (2009): 59–74. http://dx.doi.org/10.4197/med.16-3.5.
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Karima, Mamdouh. "Effect of Scaling and Root Planning with Topical Doxycycline versus Scaling and Root Planning only on the Subgingival Microbiota of Chronic Periodontitis Patients." Journal of King Abdulaziz University-Medical Sciences 17, no. 3 (2010): 55–66. http://dx.doi.org/10.4197/med.17-3.5.
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Mira, Abdulghani. "Effect of Delayed Bonding and Antioxidizing Agent on Shear Bond Strength of Resin Composite to Enamel and Dentin after Tooth Bleaching." Journal of King Abdulaziz University-Medical Sciences 18, no. 3 (2011): 65–80. http://dx.doi.org/10.4197/med.18-3.5.
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Lingawi, Sattam. "Impact of Clinical Information on Lumbar Spine MRI Evaluation of Patients Suspected of Lumbar Disk Herniation." مجلة جامعة الملك عبدالعزيز-العلوم الطبية 19, no. 3 (2012): 63–71. http://dx.doi.org/10.4197/med.19-3.5.
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Bagher, Sara, Heba Sabagh, Ahmed Mohammed, and Khloud Baghlaf. "The Relationship between Breastfeeding and Dental Caries in Preschool Children in Saudi Arabia:A Systematic Review." مجلة جامعة الملك عبدالعزيز-العلوم الطبية 20, no. 3 (2013): 53–66. http://dx.doi.org/10.4197/med.20-3.5.
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Alboog, Abdulrahman S., Taher M. Tayeb, Mohammed O. Alsager, Salwa A. AlNajjar, Ghazi A. Damanhouri, Jummanah S. Jarullah, and Salwa I. Hindawi. "Red Blood Cell Alloimmunization in Sickle Cell Disease Patients in Jeddah, Saudi Arabia: A Pilot Study." Journal of King Abdulaziz University - Medical Sciences 22, no. 3 (July 1, 2015): 34–40. http://dx.doi.org/10.4197/med.22-3.5.
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The treatment of patients with sickle cell disease frequently requires transfusion of red blood cells. Complications due to alloimmunization of red blood cells antigen remain a major risk as a post transfusion effect. The objective of this study is to determine the frequency of red cell alloimmunization in Jeddah, Saudi Arabia. A retrospective cross-section study of sickle cell disease patients at King Abdulaziz University Hospital between 2012 and 2013 was performed. Demographic characteristics and transfusion history was recorded. Blood samples were analyzed for alloimmunization using immunohematological technique. A total of 234 sickle cell patients were analyzed, of which 30 (12.8%) showed alloantibodies. A total of 43 alloantibodies were found out of which 28 belonged to Rh group, eight belonged to Kell while three belonged to MNS group. Demographic and transfusion characteristics were analyzed between alloimmunized and nonalloimmunized sickle cell disease patients. The rate of alloimmunization in Jeddah, Saudi Arabia was 12.8%. There was significant difference observed between alloantibodies detection between transfused patients compared to non-transfused patients. The consequences of red blood cell alloimmunization are highly significant and therefore immune hematological testing is highly recommended.