tbuckley/cabot-search huggingface dataset:
R-DHAOX as salvage treatment in CD20+ relapsed/refractory (R/R) non-Hodgkin lymphomas (NHL). An institutional experience
Authors: M. Rupolo, M. Spina, M. Michieli, C. Simonelli, V. Gattei, P. Bulian, M. Mazzucato, L. Abbruzzese, U. Tirelli
Journal: Journal of Clinical Oncology (2006)

17508 Background: Second line chemotherapeutic regimens in NHL are mainly based on cisplatin (DDP) and are frequently employed as cytoreductive regimens for preparation to high dose chemotherapy (HDC). The substitution of DDP with oxaliplatin in DHAP-like regimens can result in a lower toxicity and higher activity. In R/R CD20+ NHL the synergistic activity of Rituximab with chemotherapy has been shown to improve the outcome. We assessed the tolerability and efficacy of R-DHAOX (Rituximab 375 mg/m 2 , i.v. day 1, Dexametasone 40 mg i.v. days 1–4, Oxaliplatin 130 mg/m 2 i.v. day 2 and Cytarabine 2000 mg/m 2 i.v. twice a day, day 3) regimen in a fase II study including 35 pts (M/F = 22/13; median age 55 yrs, range 38–74) affected by R/R CD20+ NHL and enrolled from November 2002 until September 2005. 34 (97%) pts were staged III-IV. 31 pts (89%) were relapsed and 4 (11%) refractory. International Prognostics Index at relapse (s-IPI) was &gt;2 for 10 (71%) DLBCL, 2 (14%) FL and 2 (29%) MCL. A total of 147 cycles were administered (range 1–7). Dose reduction due to Oxaliplatin neuropathy or Cytarabine haematological toxicity occurred in 13% and in 58% of pts, respectively. NCI G3-G4 toxicities were thrombocytopenia (58%), neutropenia (55%), anaemia (13%), infection (10%) and neurotoxicity (3%). No renal failure was observed. Results spitted according to histology were summarised in the table . R-DHAOX had significant clinical activity both in FL and MCL patients (overall response rates (OR) of 93% and 86%, respectively), as well as in DLBCL (OR of 79%) despite the very high S-IPI score observed. R-DHAOX allowed adequate stem cell harvest with G-CSF mobilisation in 25/35 (71%) pts. Three-yrs projected overall survival, according to the histology, were 71% for FL, 67% for MCL and 28% for DLBCL. These data suggested that the R-DHAOX is a novel combination highly effective for R/R CD20+ NHL. [Table: see text] No significant financial relationships to disclose.
IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells
Authors: Zhiyong Yang, Chung-An M. Wu, Sasha Targ, Christopher D.C. Allen
Journal: The Journal of Experimental Medicine (2020)

IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 cytokines, with the latter promoting IgE. Here, we reevaluated this paradigm by a direct cellular analysis, demonstrating that IgE production was not limited to type 2 immune responses yet was generally constrained in vivo. IL-21 was a critical negative regulator of IgE responses, whereas IFN-γ, IL-6, and IL-10 were dispensable. Follicular helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent signaling. We reconciled previous discordant results between mouse and human B cells and revealed that the inhibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 class switch recombination was potentiated by IL-21 in the context of limited IL-4. These findings establish key features of the extrinsic regulation of IgE production by cytokines.
Coagulation abnormalities in patients with metastatic colon cancer on bevacizumab therapy
Authors: P. Fradkina, G. Locker, H. Du
Journal: Journal of Clinical Oncology (2007)

14578 Background: Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) that functions as an anti-angiogenic agent. VEGF is a glycoprotein, important for regulation of angiogenesis in normal and pathologic cells and is required for the maintenance of immature blood vessels, found in tumors. In addition to direct antiangiogenic effects, bevacizumab improves chemotherapy delivery by altering tumor vasculature as well as decreasing the size and number of liver tumors in mouse xenograft model of human colon cancer metastases. This study aimed to look for predictors of the development of major toxicities such as bleeding and clotting that would increase the incidence of such events in patients with metastatic colorectal carcinoma on Bevacizumab therapy. Methods: The study was a retrospective analysis over the past 2 years, reviewing the charts of 59 successive patients receiving bevacizumab in our institution. Particular emphasis was placed on age, gender, tumor type and location, location of metastases, chemotherapy regiment/number of cycles, past medical history, hemoglobin/hematocrit values, PT/INR values, liver function tests and albumin values at the time of the diagnosis and event. Utilizing univariant and multivariant analysis the goal was to determine contributing risk factors for increased incidence of bleeding and clotting. Results: 20.3% of the patients were found to have a major complication, such as clotting or bleeding. Once analyzed, there were four statistically significant indicators (p &lt; 0.05) that predicted for the incidence of either one of the events. They included older patient age, low albumin values at the time of the event (as defined by the institution value of less than 3.6), location of the tumor (cecum, ascending colon and sigmoid colon were predominant), and the site of the metastasis (liver and lung). Conclusions: Clotting and bleeding complications in patients on Bevacizumab are not uncommon. It is clear that age, low albumin values, metastatic site and tumor location contribute to an increased incidence of such events in patients with metastatic colon cancer on Bevacizumab therapy. [Table: see text]
Abstract P174: Adiposity Mediates the Association Between Gut Microbial Diversity and Hypertension: Cardia Study
Authors: Yuichiro Yano, Anju Lulla, Annie Green Howard, Samuel Gidding, Paul Muntner, Cora Lewis, Audrey L Blewer, Yu Hatano, Donald M Lloyd-jones, Lenore J Launer, Adam Bress, Katie A Meyer
Journal: Circulation (2020)

Introduction: We have shown that gut microbial diversity is associated with hypertension in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Animal models have documented gut microbial effects on adiposity, a known risk factor for hypertension. The extent to which adiposity may mediate the association between the gut microbiome and hypertension has not been studied. Hypothesis: We hypothesize that adiposity is a mediator of the association between gut microbial diversity and hypertension. Methods: We analyzed data from the CARDIA Study (480 participants). Shotgun metagenomic sequencing was performed on DNA extracted from stool samples collected at the Year 30 exam (2015-2016). Taxonomic classification of sequenced reads was performed using Kraken2. Within-person gut microbial diversity was assessed at the genus level using the Shannon Diversity Index and richness (number of distinct genera); lower values indicate less diversity. Hypertension was defined as systolic BP ≥140, diastolic BP ≥90 mm Hg, or taking antihypertensive medication. We performed mediation analyses to quantify the percentage of the total estimated effect of gut microbial diversity on hypertension that is mediated by adiposity as assessed using body mass index (BMI). Results: Mean age of the participants was 55.1 (3.4) years, 47% were African American, and 53% were female. In multivariable-adjusted mediation analysis, BMI explained on average 26-34% of the association between gut microbiota diversity and hypertension (Table). Results were robust to adjustment for sociodemographic variables (Model 2) and health behaviors (Model 3). Conclusions: Approximately one-third of the total effect of gut microbial diversity on hypertension is mediated through adiposity.
Differential Gene Expression of Lymphocytes Stimulated with Rhinovirus A and C in Children with Asthma
Authors: Denise Anderson, Anya C. Jones, Cibele M. Gaido, Kim W. Carter, Ingrid A. Laing, Anthony Bosco, Wayne R. Thomas, Belinda J. Hales
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Individuals with asthma have heightened antibody responses to rhinoviruses (RVs), although those specific for RV-C are lower than responses specific for RV-A, suggesting poor immunity to this species.Objectives: To ascertain and compare T-cell memory responses induced by RV-A and RV-C in children with and without asthma.Methods: Peripheral blood mononuclear cells from 17 children with asthma and 19 control subjects without asthma were stimulated in vitro with peptide formulations to induce representative species-specific responses to RV-A and RV-C. Molecular profiling (RNA sequencing) was used to identify enriched pathways and upstream regulators.Measurements and Main Results: Responses to RV-A showed higher expression of IFNG and STAT1 compared with RV-C, and significant expression of CXCL9, 10, and 11 was not found for RV-C. There was no reciprocal increase of T-helper cell type 2 (Th2) cytokine genes or the Th2 chemokine genes CCL11, CCL17, and CCL22. RV-C induced higher expression of CCL24 (eotaxin-2) than RV-A in the responses of children with and without asthma. Upstream regulator analysis showed both RV-A and, although to a lesser extent, RV-C induced predominant Th1 and inflammatory cytokine expression. The responses of children with asthma compared with those without asthma were lower for both RV-A and RV-C while retaining the pattern of gene expression and upstream regulators characteristic of each species. All groups showed activation of the IL-17A pathway.Conclusions: RV-C induced memory cells with a lower IFN-γ–type response than RV-A without T-helper cell type 2 (Th2) upregulation. Children with asthma had lower recall responses than those without asthma while largely retaining the same gene activation profile for each species. RV-A and RV-C, therefore, induce qualitatively different T-cell responses.
European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
Authors: A. Hochhaus, M. Baccarani, R. T. Silver, C. Schiffer, J. F. Apperley, F. Cervantes, R. E. Clark, J. E. Cortes, M. W. Deininger, F. Guilhot, H. Hjorth-Hansen, T. P. Hughes, J. J. W. M. Janssen, H. M. Kantarjian, D. W. Kim, R. A. Larson, J. H. Lipton, F. X. Mahon, J. Mayer, F. Nicolini, D. Niederwieser, F. Pane, J. P. Radich, D. Rea, J. Richter, G. Rosti, P. Rousselot, G. Saglio, S. Saußele, S. Soverini, J. L. Steegmann, A. Turkina, A. Zaritskey, R. Hehlmann
Journal: Leukemia (2020)

Abstract The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
Potential scenarios for the progression of a COVID-19 epidemic in the European Union and the European Economic Area, March 2020
Authors: Helen C Johnson, Céline M Gossner, Edoardo Colzani, John Kinsman, Leonidas Alexakis, Julien Beauté, Andrea Würz, Svetla Tsolova, Nick Bundle, Karl Ekdahl
Journal: Eurosurveillance (2020)

Two months after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the possibility of established and widespread community transmission in the European Union and European Economic Area (EU/EEA) is becoming more likely. We provide scenarios for use in preparedness for a possible widespread epidemic. The EU/EEA is moving towards the ‘limited sustained transmission’ phase. We propose actions to prepare for potential mitigation phases and coordinate efforts to protect the health of citizens.
下肢動脈閉塞症,上腸間膜静脈閉塞症,慢性肺血栓塞栓症を合併したプロテインC欠乏症(Val297Met)の一例
Authors: 小畠久和, 正木充, 平源善宗, 杉山祥子, 黒田忠, 寺井和生, 廣田久雄, 堀正二, 高野弘志, 澤芳樹
Journal: Circulation (2006)
AAV-mediated delivery of interferon-β for the treatment of retinoblastoma in preclinical models
Authors: C. Shih, N. Laurie, J. Holzmacher, A. Davidoff, M. Dyer
Journal: Journal of Clinical Oncology (2007)

3565 Background: Interferon-β has anti-tumor properties against a variety of malignancies through direct cytotoxicity as well as immunological effects. In order to circumvent limitations of IFN-β therapy, we have developed an adeno-associated viral gene therapy approach to deliver IFN-β directly to tumors. In this study, we tested the efficacy of AAV mediated delivery of IFN-β in preclinical retinoblastoma models. Retinoblastoma is an ideal candidate for gene-therapy based anti-cancer treatments because viral infection and IFN-β delivery can be contained within the ocular environment thereby minimizing systemic toxicity. Methods: Retinoblastoma cell lines Weri and Y79 were treated in vitro with recombinant human Interferon-β and then subjected to Viacount assays, Nexin apoptosis assays, FACS cell cycle analysis, and immunolabeling for proliferation (BrdU) and apoptosis (caspase and TUNEL). An orthotopic Xenograft retinoblastoma rat model with luciferase reporter were established and treated with single subconjunctival injection of AAV-IFN-β gene therapy. Xenogen in vivo imaging was used to follow tumor volume. Blood and tissue samples (ELISA) were obtained to determine IFN-β levels. Results: Weri and Y79 cells showed maximum reduction in viability at 500 IU/ml and 2500 IU/ml respectively. Weri response was found to be cell death by Caspase and TUNEL assay. Y79 response was found to be due to suppression of proliferation as measured by BrdU incorporation and cell cycle analysis. In the retinoblastoma xenograft model there was no increase in tumor volume by serial in vivo imaging compared to control animals. Stable levels of IFN-β were maintained at 20 ng/ml &gt;6weeks following injection. Plasma levels were undetectable 42 days following treatment. Conclusions: Retinoblastoma cell lines exhibit pleiotropic responses to IFN-β consistent with previous studies. Intravitreal injection of AAV-IFN-β resulted in efficient retinal infection and sustained IFN-β production. Viral spread outside of the eye was not detected. Using our retinoblastoma xenograft model we found that intravitreal injection of AAV-IFN-β had a potent anti-tumor effect in vivo. These data suggest that AAV mediated delivery of IFN-β may provide a complementary approach to systemic chemotherapy. No significant financial relationships to disclose.
Consistent cardiovascular (CV) benefit of empagliflozin over the spectrum of CV risk factor control in EMPA-REG OUTCOME
Authors: S.E. Inzucchi, K. Khunti, D.H. Fitchett, C. Wanner, M. Mattheus, J.T. George, A.P. Ofstad, B. Zinman
Journal: Metabolism (2020)
Abstract P220: Obesity in the Italian Adult Population: Preliminary Results of the 2018-2019 Cuore Project-health Examination Survey
Authors: Chiara Donfrancesco, Cinzia Lo Noce, Elisabetta Profumo, Brigitta Buttari, Daniela Minutoli, Anna Di Lonardo, Serena Vannucchi, Paolo Bellisario, Simona Giampaoli, Pasquale Strazzullo, Luigi Palmieri
Journal: Circulation (2020)

Introduction: Obesity is associated to an increased risk of hypertension, non-communicable diseases (NCDs), such as diabetes, coronary heart disease, stroke, and cancers, and conditions including obstructive sleep apnoea and osteoarthritis. Obesity is largely preventable and one of the WHO Global Action Plan for the Prevention of NCDs targets is to halt its rise. Hypothesis: Between 2000 and 2016, obesity trends showed a steady increase in all WHO regions and income groups. This preliminary analysis aims to assess mean level of BMI and prevalence of obesity in the Italian general adult population using the data collected within the CUORE Project-health examination survey. Methods: Within the ongoing survey started in 2018, mean of BMI and prevalence of obesity (BMI&gt;=30 kg/m 2 ) and overweight (25&lt;=BMI&lt;30 kg/m 2 ) were assessed in random samples of resident population, aged 35-74 years, stratified by age and sex (men 822 and women 869), from 8 Italian Regions in Northern, Central and Southern Italy. Weight and height were measured using standardized methodologies. A standardized questionnaire was used to collect data on education and physical inactivity. The survey is funded by the Italian Ministry of Health-CCM. Results: Mean values of BMI resulted 26.8 kg/m 2 (95% C.I. 26.5-27.1) in men and 25.9 kg/m 2 (25.6-26.3) in women. Prevalence of obesity was 19.0% (16.3-21.7) in men and 21.7% (19.0-24.5) in women; prevalence of overweight was 44.5% (41.1-47.9) in men and 28.4% (25.4-31.4) in women. Obesity levels resulted significantly higher in persons with lower education (primary or high school) vs those with higher level of education: 25.6% (20.0-31.1) vs 16.0% (13.0-19.0) in men and 32.5% (27.0-37.9) vs 16.7% (13.6-19.7) in women. Prevalence of physical inactivity during leisure time was 31.9 % (28.7-35.1) in men and 41.4% (38.2-44.7) in women. Both in men and women the prevalence of obesity was significantly higher in the Southern regions, likewise physical inactivity. Conclusions: Preliminary data of the first 8 Regions (out of 10 to be examined in the on-going survey) underline that more than half of Italian adults are in excess of weight. In comparison to data measured within the CUORE Project 10 years earlier, a slight increasing of normal weight men seems to occur moving in the direction of the WHO-NCDs obesity target.
Abstract 13224: ST Elevation Myocardial Infarction in Hospitalized Patients With Atrial Fibrillation
Authors: Fangcheng Wu, Pengyang Li, Richard A Dixon, Su Pan, Qi Liu
Journal: Circulation (2019)

Background: Atrial fibrillation (AF) is a common comorbidity and complication in patients with ST elevation myocardial infarction (STEMI), but how AF affects intervention strategy and in-hospital o...
Abstract 16: Association of Baseline &amp; Longitudinal Changes in Fitness &amp; Body Mass Index With Risk of Heart Failure in Individuals With Type 2 Diabetes Mellitus: An Analysis From the Look Ahead Trial
Authors: Ambarish Pandey, Kershaw Patel, Judy Bahnson, Darren K McGuire, Jarett D Berry, Sarah Gaussoin, Corby Martin, Ashok Balasubramanyam, Karen Johnson, Alain G Bertoni, Dalane W KITZMAN
Journal: Circulation (2020)

Introduction: Type 2 Diabetes (T2DM) is associated with higher risk for HF. The contributions of baseline measures of and changes in fitness (CRF) toward HF risk in T2DM is not well-established. Methods: Participants of the Look AHEAD trial without prevalent HF randomized to the intensive lifestyle intervention (ILI) vs. usual care arms were included. Incident HF hospitalization and its subtypes [HF with preserved ejection fraction (EF&gt;= 50%, HFpEF) &amp; HF with preserved ejection fraction (EF &lt; 50%, HFrEF)] were adjudicated through the end of 2014 using a validated approach. The associations of baseline CRF estimated from a maximal treadmill test and changes in CRF (from baseline to year 4) with risk of HF and its subtypes were evaluated using adjusted Cox models. Results: Among the 5,109 study participants, there was no significant difference in the risk of HF (n = 257 events) between the ILI vs. usual care groups [HR (95% CI) = 0.96 (0.75 - 1.23)] over 12.4 years follow up. In adjusted analysis, the risk of HF was 39% and 62% lower among moderate fit [Tertile 2] and high fit [Tertile 3] groups, respectively [vs. low fit (Tertile 1), Table]. Among HF subtypes, the risk of HFpEF was 40% lower in moderate fit and 77% lower in the high fit groups (vs. low fit). In contrast, baseline CRF was not associated with risk of HFrEF after adjustment for potential confounders (Table). BMI was also not associated with risk of HF after adjustment for CV risk factors. Among participants with repeat CRF testing (n = 3,902), improvements in CRF and weight loss over 4-year follow-up was significantly associated with lower risk of HF [HR (95% CI) per 10% increase in CRF = 0.90 (0.82 to 0.99), per 10% decrease in BMI = 0.80 (0.69 to 0.94)]. Conclusion: Higher baseline CRF is independently associated with lower risk of HF, particularly HFpEF, among individuals with T2DM. Improvements in CRF and weight loss can significantly lower risk of HF in this high-risk population. However, the ILI implemented in the LookAHEAD trial did not modify the risk of HF among the study participants.
Results of a phase III randomized controlled trial of the safety and efficacy of atrasentan in men with nonmetastatic hormone-refractory prostate cancer (HRPC)
Authors: J. B. Nelson, J. L. Chin, W. Love, C. Schulman, D. Sleep, J. Qian, J. Steinberg, P. Hintzman, M. Dawson, M. Carducci
Journal: Journal of Clinical Oncology (2007)

5018 Introduction: Atrasentan is a potent oral, selective endothelin A receptor antagonist with biological activity in patients with HRPC. This randomized phase III trial of atrasentan vs placebo was conducted in 941 men with nonmetastatic HRPC whose prostate-specific antigen (PSA) was rising despite adequate androgen suppression. Methods: 467 patients were randomized to receive atrasentan 10 mg and 474 patients were randomized to receive placebo daily. Primary efficacy endpoints were time to disease progression (TTP) and progression-free survival, with progression defined as the onset of metastases. Secondary endpoints were overall survival, time to PSA progression, change from baseline in bone alkaline phosphatase (BAP), and PSA doubling time (PSADT). Results: In the intent-to-treat population, median TTP was 764 days with atrasentan and 671 days with placebo (hazard ratio [HR], 0.915; G 1,1 P=0.288). More placebo- treated patients (267, 56.3%) than atrasentan-treated patients (227, 48.6%) experienced disease progression. Overall, 278 patients (29.5%) discontinued before reaching a protocol-defined endpoint (155, 40.8% US vs 123, 21.6% non-US). More placebo-treated patients (210, 44.3%) than atrasentan-treated patients (169, 36.2%) experienced new skeletal lesions. Median survival was 1,477 days for the atrasentan group and 1,403 days for the placebo group (HR, 0.909; G 1,1 P=0.176). Mean change from baseline to final BAP was -1.51 IU/L with atrasentan compared with +2.20 IU/L with placebo (P&lt;0.001). PSADT was lengthened with atrasentan relative to placebo (P&lt;0.031). The incidence of peripheral edema, nasal congestion, headache, dyspnea, anemia, and heart failure was significantly greater in the atrasentan group (P&lt;0.05). Most of these events were mild and nonserious and did not result in study discontinuation. Conclusions: Data from this study did not show a statistically significant difference in time to progression between atrasentan and placebo. However, the high discontinuation rate, especially among US patients, may have compromised the ability of the study to accurately determine the treatment effect of atrasentan in this population. No significant financial relationships to disclose.