tbuckley/cabot-search huggingface dataset:
Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma
Authors: Yucai Wang, Kerstin Wenzl, Michelle K. Manske, Yan W. Asmann, Vivekananda Sarangi, Patricia T. Greipp, Jordan E. Krull, Keenan Hartert, Rong He, Andrew L. Feldman, Matthew J. Maurer, Susan L. Slager, Grzegorz S. Nowakowski, Thomas M. Habermann, Thomas E. Witzig, Brian K. Link, Stephen M. Ansell, James R. Cerhan, Anne J. Novak
Journal: Blood Cancer Journal (2019)

Abstract Copy number alterations (CNAs) of 9p24.1 occur frequently in Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), primary central nervous system lymphoma, and primary testicular lymphoma, resulting in overexpression of PD-L1 and sensitivity to PD-1 blockade-based immunotherapy. While 9p24.1 CNA was also reported in diffuse large B-cell lymphoma (DLBCL), little is known about its molecular or clinical significance. In this study, we analyzed the prevalence of 9p24.1 CNA in newly diagnosed DLBCL and examined its association with PD-L1, PD-L2, and JAK2 expression, clinical characteristics, and outcome. We found that 10% of DLBCL cases had CNA of 9p24.1, with 6.5% gains, and 3.5% amplifications. Only the cases with a 9p24.1 amplification had high levels of PD-L1, PD-L2, and JAK2 expression. Gains or amplifications of 9p24.1 were associated with a younger age and the ABC/non-GCB subtype. Compared with DLBCL cases without 9p24.1 CNA, the cases with a 9p24.1 amplification had a trend of better event-free survival. Furthermore, the amplification cases had a gene expression and mutation profile similar to those of PMBCL. Our data suggest that amplification of 9p24.1 identifies a unique subset of DLBCL with clinical and molecular features resembling PMBCL that may be amenable to PD-1 blockade-based immunotherapy.
Lower costs of care, improved discharge disposition, and improved survival of advanced cancer patients (ACP) receiving early inpatient palliative care (PC) compared to standard oncologic care (SOC).
Authors: Christopher Daugherty, Julie Johnson, Stacie K. Levine, Kristen Wroblewski, Bradford Lane, William Dale, Monica Malec, Fay J. Hlubocky
Journal: Journal of Clinical Oncology (2019)

11609 Background: Outpatient PC improves ACP symptom burdens, end-of-life care transitions, and mortality thereby enhancing quality of life. Yet, the financial implications, discharge disposition, and survival benefits of early, inpatient PC compared to SOC remains less understood. Methods: Retrospective cohort analysis of ACP receiving either PC or SOC between Jan 2015-Dec 2015 (N = 810). ACP cohorts were compared for demographics, costs, disposition, and survival. Financial costs collected included: fixed (overhead expenditures, facility maintenance, hospital property); variable (patient care supplies, diagnostic/therapeutic supplies, medications); operating (fixed, variable, breaking-even costs); direct (labor, materials, commissions, piece-rate wages, manufacturing supplies); indirect (production-supervision salaries, quality control, insurance, depreciation). Univariate and multivariate analyses were completed. Results: 468 were admitted to PC and 342 to SOC. Compared with SOC, PC were more likely to be: younger (61.1±13.2 v. 62.5±13.0, p = 0.02); African American (48% v. 36%, p = 0.0045); female (50% v. 40%, p = 0.005); and have shorter length of stay (5.7±4.9 v. 6.2±6.5, p = 0.01). PC had significantly less 30-day readmissions (16% v 23%, p = 0.03) and lower costs: direct ($9,478 v. $10,416, p = 0.01); indirect ($9,538 v. $10,999, p = 0.002); fixed ($10,308 v. $12,076, p = 0.001); variable ($8,709 v. $ 9,339, p = 0.02); operating ($19,017 v. $21,416, p = 0.003).Compared with SOC, ACP receiving PC were more likely to be discharged to: home (55% v.45%, p = 0.01); healthcare facilities (e.g. skilled nursing, inpatient rehabilitation) (36.1% v. 20%, p = 0.04); and hospice (home and inpatient) (7.7% v 5.8%, p = 0.02). PC had overall greater median survival from the time of discharge (106.8±99.95 v. 73.8±61.93, p = 0.03) compared to SOC. Conclusions: Early PC results in less financial strain, greater cost savings, and improved outcomes for younger and underserved inpatient ACP. Our results provide additional evidence for policies supporting that ACP access to routine PC must become a healthcare priority.
Prim-O-glucosylcimifugin enhances the antitumour effect of PD-1 inhibition by targeting myeloid-derived suppressor cells
Authors: Wanfeng Gao, Xiaoyun Zhang, Wendong Yang, Daolei Dou, Heng Zhang, Yuanhao Tang, Weilong Zhong, Jing Meng, Yun Bai, Yanrong Liu, Lan Yang, Shuang Chen, Huijuan Liu, Cheng Yang, Tao Sun
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that play an important role in immune evasion, PD-1/PD-L1 inhibitor tolerance and tumour progression. Therefore, MDSCs are potential targets for cancer immunotherapy. In this study, we screened an effective polymorphonuclear MDSC (PMN-MDSC) inhibitor from the Traditional Chinese Medicine Library and evaluated its synergistic antitumour effects with PD-1 inhibitor. <h3>Methods</h3> In the present study, we found that PMN-MDSCs accumulate heavily in the spleen and bone marrow of melanoma (B16-F10) tumour-bearing mice. Then, we determined the top 10 key proteins in the upregulated KEGG pathways of PMN-MDSCs in tumour-bearing mice through proteomics and Cytoscape analysis. The key proteins were then used as targets for the screening of PMN-MDSC inhibitors from the traditional Chinese Medicine Library (20000 compounds) through molecular docking and weight calculation of the docking score. Finally, the inhibitory effect of the inhibitor was verified through proteomics and metabolomics analysis in vitro and melanoma (B16-F10) and triple-negative breast cancer (4 T1) mouse tumour models in vivo. <h3>Results</h3> Traditional Chinese medicine saposhnikovia root extract Prim-O-glucosylcimifugin (POG) could bind well to the target proteins and inhibit the proliferation, metabolism and immunosuppressive ability of PMN-MDSCs by inhibiting arginine metabolism and the tricarboxylic acid cycle (TCA cycle). POG could also increase CD8 T-lymphocyte infiltration in the tumours and enhance the antitumour effect of PD-1 inhibitor in B16-F10 and 4 T1 mouse tumour models. <h3>Conclusions</h3> POG was successfully screened from the traditional Chinese Medicine library as a PMN-MDSC inhibitor. POG exhibited a good synergistic antitumour effect with PD-1 inhibitor. This study provided a potential option for enhancing the efficacy of PD-1 inhibitors in clinical applications.
NICE lowers treatment threshold for high blood pressure
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Patients with hypertension aged under 80 with an estimated 10 year risk of cardiovascular disease of 10% or more should be offered blood pressure lowering drugs, new NICE guidelines state.1

The recommendation represents a large reduction in the treatment threshold for hypertension, which was previously set at 20% risk of cardiovascular disease.

NICE said that the change would have a “significant impact on practice” with many more people becoming eligible for treatment, meaning more time and resources needed to start and monitor patients on antihypertensive drugs.

Clinical management of hypertension currently accounts for 12% of visits to primary care …
Measurement of multidrug resistance in acute leukemia with three methods (Pgp expression, dnr accumulation &amp; rho accumulation)
Authors: K. Alimoghaddam, M. Alamsamimi, M. Tootoonchian, F. Nadeali, A. Ashori, A. Ghavamzadeh
Journal: Journal of Clinical Oncology (2006)

12001 Background: Multidrug resistance (MDR) is one of the most important causes of treatment failure in chemotherapy specially in acute leukemias. One of the MDR resistance mechanisms is mdr1 gene expression that causes P-glycoprotein (Pgp) expression on cell surface. Its expression and function is detected by flowcytometry. we decided to measure its expression by three method in our leukemias patients. Then we studied correlation of each of these tests with relapse, resistance, survival and some other parameters. Methods: before chemotherapy bone marrow. Pgp expression was detected with MRK16 Ab. For interpreting of Pgp we use D-value. D-value &gt;0.15 was considered positive for Pgp. For dnr accumulation &amp; rho accumulation D-value &gt;0.2 was considered positive. Informations was colleced from patient chart. Correlation of OS, DFS, resistance to therapy with Pgp expression by each method was studied. Results: there were 84 patients (52 male &amp; 32 female). 18 cases of ALL &amp; 66 cases of AML were included. Mean age was 30 ± 13 and mean of follow up was 168 ± 106 days. Mean of dPgp was 0.35 ± 0.05, mean of ddnr was 0. 5 ± 0.28 and mean of drho was 0. 5 ± 0.28 too. There was significant correlation between patients presented with first relapse and dPgp (p-value &lt; 0.009).But there was not true for ddnr or drho.Sensitivity and specifity of Pgp for resistance to therapy was 35% &amp; 75% respectively. Sensitivity and specifity of dnr accumulation for resistance to therapy was 11% &amp; 76% respectively. Sensitivity and specifity of Pgp for resistance to therapy was 11% &amp; 76% respectively. There is on significant correlation between Pgp and OS. It was true for dnr accumulation &amp; rho accumulation. RFS was longer for patients with negative Pgp, but there was not significant correlation. In patients with positive Pgp probability of relapse was 9 times more than negative Pgp. Conclusions: among these three tests Pgp expression is more useful for predicting resistance to therapy. There is no difference between dnr accumulation and rho accumulation in detecting resistance to therapy. But sensitivity of Pgp expression in detecting resistance to therapy is more than the two other tests. We can use Pgp expression as a helpful test for recognizing more resistant disease. No significant financial relationships to disclose.
A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial
Authors: Jon-David Schwalm, Tara McCready, Patricio Lopez-Jaramillo, Khalid Yusoff, Amir Attaran, Pablo Lamelas, Paul A Camacho, Fadhlina Majid, Shrikant I Bangdiwala, Lehana Thabane, Shofiqul Islam, Martin McKee, Salim Yusuf
Journal: The Lancet (2019)
Initiating epoetin-alpha (EPO) 120,000 units (U) every three weeks (Q3W) in patients with chemotherapy (CT)-induced anemia (CIA) and a hemoglobin (Hb) of &lt;11 g/dL
Authors: F. E. Wilhelm, V. Charu, J. Glaspy, V. Moyo, M. Kamin
Journal: Journal of Clinical Oncology (2007)

19589 Background: Reported here are the final Hb results for the group of patients enrolled under an amendment to a larger study that was the first to compare early vs standard intervention with EPO 120,000 U Q3W in patients with CIA and Hb of 11 to 12 g/dL. The amendment allowed for treatment of patients who had a Hb value &lt;11g/dL at screening. Methods: The larger study was a 16-week open-label randomized study that enrolled patients with non-myeloid malignancy, baseline (BL) Hb =11.0 and =12.0 g/dL, and CT planned for =9 weeks. Patients were randomized (1:1) to receive EPO 120,000 U subcutaneously Q3W immediately (early intervention group, EIG) or when their Hb fell to &lt;11.0 g/dL (standard intervention group, SIG). If, at any dosing visit after the first EPO dose, Hb decreased to &lt;10.0 g/dL, patients were switched to EPO 40,000 U weekly (QW). An amendment was added to the larger study to allow similar patients whose Hb was &lt;11 g/dL at screening to be treated with EPO 120,000 U Q3W. EPO was withheld for Hb &gt;13.0 g/dL at any dosing visit; dose was reduced for Hb &gt;12.0 g/dL or Hb increase &gt;1.5 g/dL in a 3-week period (current prescribing information recommends target Hb not to exceed 12 g/dL). Hb response was analyzed using an observed case approach and Hb data following switch to 40,000 U QW were censored. Results: Fifty patients were enrolled under the amendment. BL characteristics were: mean age, 62.0 years; 67% female; mean Hb 10.1 g/dL. Mean Hb changes over time from BL for patients receiving Q3W dosing are shown in the table . PRBC transfusion rate after 4 weeks on treatment was 24.5%. 18.0% of patients had at least one dose withheld and 22.0% had at least one dose reduction. Five deaths and 6 clinically relevant TVEs were reported. Conclusions: This study shows that EPO is effective in raising Hb when initiated in patients with CIA and a Hb of &lt;11 g/dL at 120,000 U every 3 weeks. Further studies are warranted. No significant financial relationships to disclose. [Table: see text]
Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial
Authors: Mansoor Raza Mirza, Elisabeth Åvall Lundqvist, Michael J Birrer, Rene dePont Christensen, Gitte-Bettina Nyvang, Susanne Malander, Maarit Anttila, Theresa L Werner, Bente Lund, Gabriel Lindahl, Sakari Hietanen, Ulla Peen, Maria Dimoula, Henrik Roed, Anja Ør Knudsen, Synnöve Staff, Anders Krog Vistisen, Line Bjørge, Johanna U Mäenpää
Journal: The Lancet Oncology (2019)
Abstract 13133: Cardiovascular Abnormalities and Their Adverse Influence on Mortality in Patients With Intracranial Hemorrhage: A Meta-Analysis
Authors: Saraschandra Vallabhajosyula, Toufik Mahfood Haddad, Amjad Kabach, Arun Kanmanthareddy, Lee E Morrow, Dennis J Esterbrooks
Journal: Circulation (2015)

Introduction: Intracranial hemorrhage (ICH) is associated with high mortality rate of 30-52% despite current advances in management. New cardiovascular abnormalities (CA), such as EKG or cardiac biomarker abnormalities ensue in ICH and are postulated to be due to hypothalamic injury and catecholamine surge. These CA are thought to portend a poor prognosis. Methods: We evaluated clinical studies reporting CA in ICH and assessing their effect on mortality. Studies without a control group, pediatric, and non-English literature were excluded. We extracted data on demographics, comorbidities and mortality [in-hospital (IHM), 30 day (30M) and 90 day (90M)]. CA data included EKG changes (bradycardia, atrial fibrillation, bundle branch blocks, QTc prolongation, ST-segment depression, and ST-segment elevation), biomarker elevation (troponin-T (TnT), CK-MB and BNP), and wall motion abnormalities (WMA). Unadjusted and adjusted rates for CA and pooled risk ratio (RR) with 95% CI were calculated using Mantel-Haenszel random effects model for mortality. Results: We reviewed 453 studies, of which 26 met our inclusion criteria. Heterogeneity varied from moderate to severe depending on the outcome chosen. Of a total 5580 patients, 2796 (50.1%) had sub-arachnoid hemorrhage (SAH), 1633 ICH (29.3%) and 1151 (20.6%) both. The incidence of CA is presented in Table 1. Of these 26 studies, 19 evaluated the influence of new CA on mortality. IHM was noted in 175/566 (30.9%) and 491/2496 (19.7%) patients with and without CA, respectively. In addition, 30M and 90M were noted in 18/38 (47.4%) vs. 14/136 (10.3%) and 90/175 (51.4%) vs. 247/1139 (21.7%) patients with and without CA, respectively. CA was associated with worse IHM (RR 2.03, 95% CI 1.58-2.62, p&lt;0.001), 30M (RR 3.18, 95% CI 1.86-5.42, p&lt;0.001) and 90M (RR 2.11, 95% CI 1.44-3.08, p&lt;0.001) in patients with ICH compared to those who did not have CA. Conclusion: CA are common in patients with ICH and are associated with worse IHM, 30M and 90M.
Multidisciplinary treatment of 99 adult osteosarcoma (OST) patients (pts) with synchronous and metachronous metastases (mets): A retrospective series of the French Sarcoma Group (FSG).
Authors: Elise Lavit, Mihaela Aldea, Nicolas Isambert, Jean-Emannuel Kurtz, Corinne Delcambre, Valerie Lebrun-Ly, Pauline Soibinet-Oudot, Christine Chevreau, Emmanuelle Bompas, Christine Le Maignan, Pascaline Boudou-Rouquette, Axel Le Cesne, Julien Mancini, Jean-Yves Blay, Florence Duffaud
Journal: Journal of Clinical Oncology (2019)

11030 Background: Treatment (trt) options for metastatic OST are scarce. Following failure of standard 1st line therapy pts who relapse present a challenging trt dilemma, and have poor prognosis. Surgical removal of all mets is essential. Currently, there are no standardized 2nd line trt options in relapsed OST. Methods: Pts were identified from 2 sarcoma databases; Netsarc and ConticaBase. Clinical data prospectively registered in the databases were supplemented with retrospective review of the medical records. Results: From January 2009 to December 2016, we identified 99 pts, in 12 FSG centers; 30 with synchronous (SC) and 69 with metachronous (MC) mets, with 62 males. Median age was 25 years (18-53). Total number of mets was 1 for 31 pts, 2-5 for 26 and &gt; 5 for 42. Mets sites were lung, bone and other in 77, 14 and 22 pts respectively. Median time to first MC mets was 22 months (mo) (4-97). All pts except 10 with MC mets received a 1st line systemic trt for relapse, 65 a 2d-line, 38 a 3d-line, and 20 a 4th line, with 27 pts included in a clinical trial. Sixty five pts had local trt of distant mets (surgery for 54, irradiation for 5 and radioablation for 6). Eighteen pts had repeated thoracotomies (2 for 13 pts, 3 for 5, 1 for 1 pt). Nine of 10 MC mets pts (with ≤ 5mets) who never received any systemic trt had complete mets resection, 1 had mets radioablation, all were alive at last follow-up (FU). Median FU was 16.5 mo (2-132). Median progression free survival (PFS) and overall survival (OS) were 5.5 (95%CI 4-7) and 16.5 mo (95%CI 10-25) respectively. In multivariate analysis; &gt; 5 mets, time to 1st mets &lt; 24 mo, were negative prognostic factors on OS and PFS (p= 0.03, 0.01 and p=0.013, 0.00 respectively). Bone mets and absence of mets surgery were negative prognostic factors on OS only (with p=0.012, 0.008). Conclusions: Adult OST pts with distant mets are heterogeneous with poor prognosis. Complete surgery of distant mets remains essential. In reference sarcoma center, OST pts at relapse with &gt; 1 mets commonly receive &gt;1st line of systemic trt, and are included in clinical trial. Multidisciplinary trt combining complete mets local trt and systemic therapy seems to be rational.
<i>Notes from the Field:</i> Mumps in Detention Facilities that House Detained Migrants — United States, September 2018–August 2019
Authors: Jessica Leung, Diana Elson, Kelsey Sanders, Mona Marin, Greg Leos, Brandy Cloud, Rebecca J. McNall, Carole J. Hickman, Mariel Marlow
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
Pathogenic Germline Variants in Acquired Aplastic Anemia (AA) and Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Wenyi Shen, Cassandra M. Hirsch, Bartlomiej P. Przychodzen, Hideki Makishima, Louis Williams, Sudipto Mukherjee, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2018)
Differential Activation of the Transcription Factor IRF1 Underlies the Distinct Immune Responses Elicited by Type I and Type III Interferons
Authors: Adriana Forero, Snehal Ozarkar, Hongchuan Li, Chia Heng Lee, Emily A. Hemann, Marija S. Nadjsombati, Matthew R. Hendricks, Lomon So, Richard Green, Chandra N. Roy, Saumendra N. Sarkar, Jakob von Moltke, Stephen K. Anderson, Michael Gale, Ram Savan
Journal: Immunity (2019)
Assessing the Justification, Funding, Success, and Survival Outcomes of Randomized Noninferiority Trials of Cancer Drugs
Authors: Bishal Gyawali, Frazer A. Tessema, Emily H. Jung, Aaron S. Kesselheim
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Noninferiority trials test whether a new intervention is not worse than the comparator by a given margin. <h3>Objectives</h3> To study the characteristics of published randomized noninferiority trials in oncology with overall survival as an end point, to assess the association of justification and success in achieving noninferiority with the funding of these trials, and to evaluate the association of such trials with patient survival. <h3>Data Sources</h3> A systematic search of PubMed and Google Scholar databases was conducted in March 2018, with no date restrictions. <h3>Study Selection</h3> Randomized noninferiority trials of cancer drug therapies with overall survival as an end point were included. Trials of decision support, supportive care, and nondrug treatment in both arms were excluded. <h3>Data Extraction and Synthesis</h3> This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for meta-epidemiological studies. Studies were screened for eligibility criteria, and data on criteria for noninferiority, funding, success (achieving noninferiority), and hazard ratios with confidence intervals for overall survival were extracted. Hazard ratios for overall survival were pooled across trials using a random-effects model. <h3>Main Outcomes and Measures</h3> Associations of the justification for using a noninferiority design and success in achieving noninferiority with the source of funding were assessed. Overall pooled hazard ratios and confidence intervals for overall survival were calculated. <h3>Results</h3> Among 74 noninferiority trials of cancer drug therapies, 23 (31%; enrolling 21 437 patients) used overall survival as the primary end point. The noninferiority margins for the hazard ratio of overall survival ranged from 1.08 to 1.33. Noninferiority design was justified in 14 trials (61%) but not in 9 (39%). Overall, 18 trials (78%) concluded with a finding of noninferiority. Industry funding was associated with lack of justification for noninferiority design (<i>P</i> = .02, assessed using the Fisher exact test) but not with success in proving noninferiority (<i>P</i> = .80, assessed using the Fisher exact test). When the hazard ratios across the trials were pooled, there was no beneficial or detrimental association with overall survival, with a pooled hazard ratio of 0.97 (95% CI, 0.92-1.02). <h3>Conclusions and Relevance</h3> The findings suggest that a substantial fraction of noninferiority trials in oncology, most of which are industry funded, lack justification for such a design. Greater attention to the use of noninferiority designs in randomized clinical trials of cancer drugs from local and national regulators is warranted.