tbuckley/cabot-search huggingface dataset:
Proteomic prediction in hormone receptor-positive breast cancer
Authors: B. T. Hennessy, A. M. Gonzalez-Angulo, Y. Lu, R. Tibes, D. Siwak, A. Sahin, S. Kau, G. N. Hortobagyi, V. Valero, G. B. Mills
Journal: Journal of Clinical Oncology (2006)

541 Background: Hormone receptor-positive breast cancer (HR+BC) is heterogeneous. Attempts to use transcriptional analysis such as Oncotype Dx facilitate therapy planning but fail to identify patients who will relapse or potential therapy targets. Methods: We used reverse phase protein lysate arrays and Microvigene software to quantify expression of estrogen receptor (ERα) and 36 total/activated components of the HER2, phosphatidylinositol-3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and STAT pathways in 64 HR+BCs and 40 breast cancer cell lines. Clustering was performed with Xcluster and Treeview. Results: 47/64 HR+BC patients were treated with adjuvant hormone therapy and 43/64 with chemotherapy. There were 12 recurrences including 5 patients diagnosed with metastases within 0–3 months of diagnosis. Unsupervised analysis using the expression of all 37 proteins revealed two large subclusters of HR+BCs. One large cluster was composed of tumors with lower ERα expression levels and was driven by an antibody group composed mostly of phosphoproteins indicative of activated growth factor signaling pathways. Thus, there were significant inverse correlations between ERα expression and the expression and activation of components of the PI3K/MAPK pathways including EGFR, src, AKT, 4EBP1, and PKCα (p≤0.05 for each). Similar inverse correlations were seen in 40 assayed breast cancer cell lines. The clinicoproteomic predictors of relapse among HR+BCs were nuclear grade (p=0.001), low expression of ERα (p=0.04), low p38 phosphorylation (p=0.02), and high p53 (p=0.02). There also was a trend (p≤0.1) to the association of low MAPK and S6 phosphorylation, low p27, and high cyclin B1 with relapse. Using these antibodies to perform a supervised analysis, we found a small group of p53-high, cyclin B1-high, ERα-low HR+BCs with a 75% likelihood of relapse, significantly greater than in other tumors (p&lt;0.003). Since 10/12 relapses occurred in 26 grade 3 tumors, we searched for and found a ‘grade 3’ HR+BC 6 antibody signature associated with a recurrence-free survival at 20 months of 17% compared to 100% in other patients (p=0.002). Conclusion: Although patient numbers are small and the findings require validation, kinase signaling profiles have potential in breast cancer prediction. No significant financial relationships to disclose.
Acute Myeloid Leukemia (AML-M2) with a Novel Translocation t(5;11)(q35;q13) and Normal Expression of Cyclin D1.
Authors: Fabio M. de Oliveira, Guilherme A.S. dos Santos, Andre F. Marinato, Amelia G. Araujo, Ana S.G. Lima, Rafael H. Jacomo, Roberto P. Falcao, Luis G. Tone, Belinda P. Simoes, Eduardo M. Rego
Journal: Blood (2005)
Can Addition of GM-CSF in Adult Haplo-Identical Transplant Who Cannot Benefit from NK Alloreactivity Improve the Relapse Rate of Advanced Leukemia: A 3 Step Study.
Authors: Philippe Lewalle, Alain Delforge, Berengere Nowak, Virginie Misplon, Laurence Lagneaux, Koen Theunissen, Jalil Bennani, Dominique Bron, Philippe Martiat
Journal: Blood (2004)
Implementation of Lung Cancer Screening in the Veterans Health Administration
Authors: Linda S. Kinsinger, Charles Anderson, Jane Kim, Martha Larson, Stephanie H. Chan, Heather A. King, Kathryn L. Rice, Christopher G. Slatore, Nichole T. Tanner, Kathleen Pittman, Robert J. Monte, Rebecca B. McNeil, Janet M. Grubber, Michael J. Kelley, Dawn Provenzale, Santanu K. Datta, Nina S. Sperber, Lottie K. Barnes, David H. Abbott, Kellie J. Sims, Richard L. Whitley, R. Ryanne Wu, George L. Jackson
Journal: JAMA Internal Medicine (2017)

The US Preventive Services Task Force recommends annual lung cancer screening (LCS) with low-dose computed tomography for current and former heavy smokers aged 55 to 80 years. There is little published experience regarding implementing this recommendation in clinical practice.To describe organizational- and patient-level experiences with implementing an LCS program in selected Veterans Health Administration (VHA) hospitals and to estimate the number of VHA patients who may be candidates for LCS.This clinical demonstration project was conducted at 8 academic VHA hospitals among 93 033 primary care patients who were assessed on screening criteria; 2106 patients underwent LCS between July 1, 2013, and June 30, 2015.Implementation Guide and support, full-time LCS coordinators, electronic tools, tracking database, patient education materials, and radiologic and nodule follow-up guidelines.Description of implementation processes; percentages of patients who agreed to undergo LCS, had positive findings on results of low-dose computed tomographic scans (nodules to be tracked or suspicious findings), were found to have lung cancer, or had incidental findings; and estimated number of VHA patients who met the criteria for LCS.Of the 4246 patients who met the criteria for LCS, 2452 (57.7%) agreed to undergo screening and 2106 (2028 men and 78 women; mean [SD] age, 64.9 [5.1] years) underwent LCS. Wide variation in processes and patient experiences occurred among the 8 sites. Of the 2106 patients screened, 1257 (59.7%) had nodules; 1184 of these patients (56.2%) required tracking, 42 (2.0%) required further evaluation but the findings were not cancer, and 31 (1.5%) had lung cancer. A variety of incidental findings, such as emphysema, other pulmonary abnormalities, and coronary artery calcification, were noted on the scans of 857 patients (40.7%).It is estimated that nearly 900 000 of a population of 6.7 million VHA patients met the criteria for LCS. Implementation of LCS in the VHA will likely lead to large numbers of patients eligible for LCS and will require substantial clinical effort for both patients and staff.
Incidence des néoplasies avancées chez les patients à haut risque et à risque intermédiaire selon les définitions européennes des programmes de dépistage du cancer colo-rectal
Authors: N. Musquer
Journal: Endoscopy (2016)

Dans le cadre des politiques de dépistage et de surveillance du CCR, nos instances européennes stratifient les patients en 3 niveaux de risque dépendant des constatations faites lors des coloscopies: faible risque (1 à 2 adénomes tubuleux de moins de 10 mm), risque intermédiaire (3 à 4 adénomes dont au moins un avec soit une composante villeuse, soit une taille de 10 à 19 mm, soit une dysplasie de haut grade) et haut risque (5 à 9 adénomes ou un adénome de plus de 19 mm). Pour les groupes à risque intermédiaire et à haut risque, une coloscopie de contrôle à 3 ans et à 1 an respectivement est recommandée.
The Incidence of Bcr-Abl Mutations and Their Impact on Clinical Outcome in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Patients Treated with Bosutinib Versus Imatinib in the BELA Trial
Authors: Dong-Wook Kim, Jorge E Cortes, Zvenyslava Maslyak, Raymond Wong, Ladan Duvillie, Christine Powell, Athena Countouriotis, Tim H Brümmendorf
Journal: Blood (2011)
Overall Survival Patterns in Patients with Multiple Myeloma in the Era of Novel Agents and the Role of Initial Clinical Presentation and Comorbidities: A Population-Based Study
Authors: Berdien Oortgiesen, Eric N. van Roon, Peter Joosten, Robby Kibbelaar, Huib Storm, Sjoerd Hovenga, Bas P Van Rees, Gerhard Woolthuis, Nic J.G.M. Veeger, Mels Hoogendoorn
Journal: Blood (2014)
Phase II study of capecitabine and gemcitabine in patients with metastatic colorectal cancer (mCRC)
Authors: S. Iqbal, D. Yang, S. Cole, A. B. El-Khoueiry, W. Boswell, R. Agafitei, R. Lujan, H. J. Lenz
Journal: Journal of Clinical Oncology (2009)

e15077 Background: Failing standard chemotherapy, many mCRC patients (pts) maintain an adequate performance status necessitating therapeutic options. Preclinical data in CRC cell lines shows that 5-FU and gemcitabine have synergistic cytotoxicity by stabilization of thymidylate synthase resulting in stronger inhibition of DNA synthesis. Methods: The primary objective was to assess time to progression (TTP) in mCRC pts who had progressed on irinotecan and oxaliplatin therapy. Secondary objectives included response rate (RR), overall survival (OS), toxicity and correlates to assess genes in the 5-FU, gemcitabine pathways. This single center study was a two stage minimax design. A ≤ 30% chance of progressing within the first 6 weeks would be promising. 27 pts were enrolled in the first stage, if ≥ 13 progressed (or had unacceptable toxicity) prior to 6 weeks then the study would be terminated. The planned sample size was 53 pts. A cycle was defined as capecitabine 650 mg/m2 BID days 1–14 and gemcitabine 1,000 mg/m2 i.v. over 100 minutes days 1, 8. Results: The study met its first stage goal and continued to accrue 54 eligible pts (male 24/female 30), median age 58 years (range 31–78). Pts received a median of 2 cycles (range 1–19), with 22% of pts receiving 6 + cycles. Three pts that withdrew shortly after start were excluded from toxicity analysis. Of 51 pts, 23 had Grade 3/4 drug related toxicity, commonly 9 pts ANC/AGC; 4 pts pain. The probability of progressing at 6 weeks was .46 + .07, with 23 pts progressing or dying within that time. Median OS was 5.9 months (95% CI 4.3, 8.7), PFS was 8.1 weeks (95% CI 5.6, 11.6). Of 48 pts evaluable for response, 17 had stable disease, for these pts, the median PFS was 4.3 months (95%CI: 3.9–8.8) and OS 10 months (95%CI: 7.9–16.6); 31 had progressive disease or symptomatic deterioration. Conclusions: The combination of gemcitabine and capecitabine in refractory mCRC was well tolerated. Unfortunately, the study did not meet the primary endpoint, but there appears to be a subset of pts with stable disease who may benefit from therapy. Correlatives are pending. [Table: see text]
Validation of German High-Grade Non-Hodgkin's Lymphoma (DSHNHL) Prognostic Model and the Impact of Treatment on Secondary Central Nervous System (CNS) Relapse in Diffuse Large B-Cell Lymphoma (DLBCL) in a Developing Country: Report from the Nationwide Multi-Institutional Registry of Thai Lymphoma Study Group (TLSG)
Authors: Kitsada Wudhikarn, Udomsak Bunworasate, Arnuparp Lekhakula, Jakrawadee Julamanee, Chittima Sirijerachai, Kanchana Chansung, Lalita Norasetthada, Weerasak Nawarawong, Archrob Khuhapinant, Supachai Ekwattanakit, Tontanai Numbenjapon, Kannadit Prayongratana, Suporn Chuncharunee, Pimjai Niparuck, Tawatchai Suwanban, Nonglak Kanitsap, Somchai Wongkhantee, Rachanid Pornvipavee, Peerapon Wong, Nisa Makruasi, Pannee Praditsuktavorn, Tanin Intragumtornchai
Journal: Blood (2015)
NICE publishes guideline on diagnosing and managing cerebral palsy in young people
Authors: Ingrid Torjesen
Journal: BMJ (2017)

The National Institute for Health and Care Excellence (NICE) has published its first dedicated guideline on diagnosing and managing cerebral palsy in under 25s, in an attempt to improve recognition and treatment of the condition.1

Cerebral palsy is the most common cause of physical disability in children and young people in the developed world, affecting around one in 400 babies born in the UK.

Previously, NICE had published recommendations on managing the motor difficulties of cerebral palsy only as part of a 2012 guideline on managing spasticity in under 19s. The new guideline focuses on the risk factors …
Wearable Technology and Long-term Weight Loss
Authors: Timothy B. Plante, Seth S. Martin
Journal: JAMA (2017)

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Use of Cardiac Resynchronization Therapy Among Eligible Patients Receiving an Implantable Cardioverter Defibrillator
Authors: Lucas N. Marzec, Pamela N. Peterson, Haikun Bao, Jeptha P. Curtis, Frederick A. Masoudi, Paul D. Varosy, Steven M. Bradley
Journal: JAMA Cardiology (2017)

Cardiac resynchronization therapy (CRT) reduces the risk for mortality and heart failure-related events in select patients. Little is known about the use of CRT in combination with an implantable cardioverter defibrillator (ICD) in patients who are eligible for this therapy in clinical practice.To (1) identify patient, clinician, and hospital characteristics associated with CRT defibrillator (CRT-D) use and (2) determine the extent of hospital-level variation in the use of CRT-D among guideline-eligible patients undergoing ICD placement.Multicenter retrospective cohort from 1428 hospitals participating in the National Cardiovascular Data Registry ICD Registry between April 1, 2010, and June 30, 2014. Adult patients meeting class I or IIa guideline recommendations for CRT at the time of device implantation were included in this study.Implantation of an ICD with or without CRT.A total of 63 506 eligible patients (88.6%) received CRT-D at the time of device implantation. The mean (SD) ages of those in the ICD and CRT-D groups were 67.9 (12.2) years and 68.4 (11.5) years, respectively. In hierarchical multivariable models, black race was independently associated with lower use of CRT-D (odds ratio [OR], 0.77; 95% CI, 0.71-0.83) as was nonprivate insurance (OR, 0.90; 95% CI, 0.85-0.95 for Medicare and OR, 0.73; 95% CI, 0.65-0.82 for Medicaid). Clinician factors associated with greater CRT-D use included clinician implantation volume (OR, 1.01 per 10 additional devices implanted; 95% CI, 1.01-1.01) and electrophysiology training (OR, 3.13 as compared with surgery-boarded clinicians; 95% CI, 2.50-3.85). At the hospital level, the overall median risk-standardized rate of CRT-D use was 79.9% (range, 26.7%-100%; median OR, 2.08; 95% CI, 1.99-2.18).In a national cohort of patients eligible for CRT-D at the time of device implantation, nearly 90% received a CRT-D device. However, use of CRT-D differed by race and implanting operator characteristics. After accounting for these factors, the use of CRT-D continued to vary widely by hospital. Addressing disparities and variation in CRT-D use among guideline-eligible patients may improve patient outcomes.
Infectious Zika virus in vaginal secretions from an HIV-infected woman, France, August 2016
Authors: Pauline Penot, Ségolène Brichler, Jean Guilleminot, Caroline Lascoux-Combe, Olivier Taulera, Emmanuel Gordien, Isabelle Leparc-Goffart, Jean-Michel Molina
Journal: Eurosurveillance (2017)

A woman with controlled HIV infection developed in late August 2016 a pruritic rash with fever and conjunctival hyperaemia after a trip to the French Caribbean islands. On day 3 after symptom onset, Zika virus RNA was detected in plasma, urine and vaginal samples with respective viral loads of 3.8, 6.1 and 5.3 log copies/mL. Notably, we demonstrated the presence of infectious Zika virus particles in the vaginal samples by isolation in cell culture.
A phase II study of PROSTVAC-VF vaccine, and the role o f GM-CSF, in patients (pts) with metastatic androgen insensitive prostate cancer (AIPC)
Authors: J. L. Gulley, N. Todd, W. Dahut, J. Schlom, P. Arlen
Journal: Journal of Clinical Oncology (2005)

2504 Background: Vaccine strategies represent a novel therapeutic approach for the treatment of metastatic AIPC. Preclinical and clinical studies have demonstrated that the induction of T-cell responses directed against a PSA can lead to anti-tumor activity in the absence of toxicity. Two novel PSA-based vaccines have been developed: (a) a recombinant (r) vaccinia virus containing the entire PSA transgene with a modified agonist epitope and three costimulatory molecule transgenes, rV-PSA-TRICOM (rV) and (b) a similar recombinant fowlpox virus, rF-PSA-TRICOM (rF). We have completed a phase I study demonstrating the clinical safety of a prime/boost vaccine strategy: priming with rV with subsequent monthly boosts using rF. Methods: This phase II study randomizes 32 pts with metastatic AIPC without prior chemotherapy and progressive disease into one of the following 4 cohorts utilizing the same vaccine used in the phase I study. Pts randomized to cohort 1 receive vaccine alone, pts in cohort 2 receive vaccine with recombinant GM-CSF protein, and pts in cohorts 3 and 4 receive vaccine with 2 different doses of fowlpox-GM-CSF. Pts receive restaging scans every 3 months while on study and may continue to receive vaccine until disease progression. Results: To date, 25 pts have enrolled on study and 16 have undergone restaging evaluation at 3 months. Five of these pts have demonstrated PSA declines during this period, 4 pts with PSA declines of >30% and 1 pt with a decline of >50%. Eleven of 23 pts continue on treatment with 6 of 20 pts continuing on study beyond the initial 3-month period. One patient at 8 months has experienced a PR by RECIST criteria with >50% decrease in unidimensional measurement of his hilar adenopathy. Another pt who remains with stable disease after 10 months of treatment has had a 29% decrease in his soft tissue disease. A third pt on study for 11 months continues to have stable disease. Immunologic studies are planned to monitor pts immune responses measuring changes in PSA specific T cells. Conclusions: This vaccine can be given safely and has been associated with declines in PSA in several pts with one pt having an impressive decrease in his soft tissue lesion. No significant financial relationships to disclose.
Updated results of a prospective noninterventional study of everolimus after failure of the first VEGF-targeted therapy.
Authors: Michael D. Staehler, Peter J. Goebell, Ulrich Kube, Manfred Kindler, Thomas Koepke, Jan Janssen, Joerg Schmitz, Steffen Weikert, Susanne Kloss, Gabriel Steiner, Andreas Jakob, Thomas Steiner, Friedrich Overkamp, Lothar Bergmann, Gernot Guderian, Christian Doehn
Journal: Journal of Clinical Oncology (2012)

361 Background: Everolimus (EVE, Afinitor) is approved for the treatment of metastatic renal cell cancer (mRCC) after failure of VEGF-targeted therapy. The option to treat mRCC with six approved targeted agents has sparked debate on proper sequencing of these agents. However, data beyond clinical trials is limited. Here, we report prospective non-interventional data on EVE in routine use after failure of the first VEGF-targeted therapy. Methods: A prospective, single arm, open label, multi center non-interventional study for patients with mRCC was initiated in Germany in 08/2009 to determine effectiveness defined as time between first EVE intake until disease progression due to any cause (TTP) and treatment duration. Targeted enrollment is 400 patients. A first interim analysis was conducted 3 months after 100 patients had been enrolled and was presented previously (Bergmann et al., J Clin Oncol 29: 2011 [suppl; abstr 4552]). Here we present a second interim analysis to corroborate the results of the first interim analysis. Patients were analyzed 14 months after the first 100 patients had been enrolled. Results: 59 sites included 113 patients between August 2009 and July 2010. At the cut-off date of the first interim analysis (12 November 2011), these patients had been followed for a median of 116 days. The safety population consisted of 99 patients with documented EVE treatment. The median treatment duration had not yet been reached at the time of the first interim analysis. Median time to progression (TTP) was 9.7 months (95% CI: 6 months; n.d.). A total of 230 AEs were reported in 61% of patients including 18 SAEs in 12 patients (12%). These preliminary results are substantiated in this interim analysis with a total observation period of at least 14 months (cut-off date 30 September 2011). Updated data on effectiveness and safety of EVE will be presented. Conclusions: This non-interventional study on EVE in treatment of mRCC after prior failure of VEGF-targeted therapy provides first evidence on routine use of EVE. Further analysis of this ongoing study affords insight into effectiveness and safety of EVE in routine use after failure of the first VEGF-targeted therapy.
Long-Term Outcome of High-Dose Sequential Chemotherapy with Autografting (i-HDS) in Follicular Lymphoma at Diagnosis: An Update of the Prospective Multicenter Consecutive Trial of the "Gruppo Italiano Trapianto Di Midollo Osseo" (Gitmo).
Authors: Marco Ladetto, Sonia Vallet, Paolo Corradini, Fabio Benedetti, Umberto Vitolo, Maurizio Martelli, Vincenzo Callea, Paolo Coser, Alessio Perrotti, Caterina Patti, Giuseppe Fioritoni, Sergio Morandi, Maurizio Musso, Renato Zambello, Monica Astolfi, Alessandro Pileri, Mario Boccadoro, Corrado Tarella
Journal: Blood (2004)
LVAD-DT: Culture of Rescue and Liminal Experience in the Treatment of Heart Failure
Authors: Frances K. Barg, Katherine Kellom, Tali Ziv, Sarah C. Hull, Selena Suhail-Sindhu, James N. Kirkpatrick
Journal: The American Journal of Bioethics (2017)

The purpose of this article is to investigate how cultural meanings associated with the left ventricular assist device (LVAD) inform acceptance and experience of this innovative technology when it is used as a destination therapy. We conducted open-ended, semistructured interviews with family caregivers and patients who had undergone LVAD-DT procedures at six U.S. hospitals. A grounded theory approach was used for the analysis. Thirty-nine patients and 42 caregivers participated. Participants described a sense of obligation to undergo the procedure because of its promise for salvation. However, once the device was implanted, patients described being placed into a liminal state of being neither sick nor healthy, with no culturally scripted role. Consideration of end-of-life decisions was complicated by the uncertainties about how patients with LVADs die. Pre-implantation communications among patient, family, and clinicians should take into account the impact of the technology on meaning, identity, and patient experience.