tbuckley/cabot-search huggingface dataset:
Predictors of survival in advanced renal cell carcinoma (RCC): Long-term results from Southwest Oncology Group trial S8949
Authors: S. Conlon, C. M. Tangen, R. C. Flanigan, E. D. Crawford, P. N. Lara
Journal: Journal of Clinical Oncology (2008)

5042 Background: S8949 demonstrated improved overall survival (OS) for palliative debulking nephrectomy in interferon-treated RCC patients (Flanigan, NEJM 2004). We explored clinical predictors of OS in an updated analysis with a median follow-up time of 9 years. Methods: Univariate and multivariate Cox regression analyses were performed to evaluate the impact of clinical variables potentially influencing OS (including performance status [PS] & early progressive disease [PD], among others). Results: 246 patients with advanced or metastatic RCC were randomized to interferon with or without nephrectomy. Of the 241 evaluable patients, median age was 59 years, 167 (69%) were male and 125 (52%) had PS 1. Patients randomized to nephrectomy had improved OS (Hazard Ratio [HR] 0.74, 95% CI 0.57–0.96 p=0.022), confirming the original report. Univariate analysis showed PS=1 (p<0.0001), hemoglobin below the median (p=0.015), and early PD within 90 days (p<0.0001) as poor prognostic factors. Multivariate analysis showed PS 1 vs. 0 (HR 1.95, p<0.0001), high alkaline phosphatase (HR 1.5, p=0.002) and lung metastases only (HR 0.73, p=0.028) as OS predictors, but not nephrectomy (HR 0.78, p=0.07). There was no evidence of an interaction of PS, hemoglobin or lung metastases with nephrectomy (all P>0.20). In a patient subset surviving at least 90 days, early PD was also significant in a multivariate model (HR 2.1, p<0.0001) as was PS (HR 1.7, p=0.0006). Conclusions: Nephrectomy prolongs long-term OS in this mature analysis, supporting its role as standard therapy for advanced RCC patients. Early PD (within 90 days) and PS were strong predictors of OS. The benefit from nephrectomy was seen across all patient subsets. These results support current efforts to identify biomarkers of RCC treatment resistance and early PD to facilitate rational patient selection for systemic therapy. No significant financial relationships to disclose.
Long-term survival and long-lived immune memory in patients with metastatic melanoma vaccinated with melanoma-antigen loaded dendritic cells.
Authors: A. K. Palucka, H. Ueno, G. Goldberg, A. Israyelyan, F. Marches, L. Bourdery, J. W. Fay, J. Banchereau
Journal: Journal of Clinical Oncology (2010)

e19018 Background: Clinical trials have demonstrated the safety of cancer antigen-loaded dendritic cells (DCs) as well as clinical and immune responses. We showed that antigen-pulsed DCs administered to patients with metastatic melanoma are immunogenic and can induce durable objective clinical responses even in patients who failed previous therapy. Here we analyzed long term immunological outcomes in our cohort of vaccinated patients. Methods: Between March 1999 and February 2005 sixty four patients with metastatic melanoma were treated with DCs vaccines in the course of four phase I/IIa clinical trials. DCs were generated either from CD34+ hematopoietic progenitors or from blood monocytes. Forty nine (49) HLA-A*0201+ patients received vaccines pulsed with melanoma antigen derived peptides (MART-1, MAGE-3, TYR and gp100). Twenty one patients received DCs loaded with killed allogeneic tumors regardless of their HLA type. KLH was used as a helper antigen and, in HLA- A*0201+ patients, Flu-M1 peptide was used as the control antigen. Patients received up to eight vaccinations with antigen-loaded DCs over a maximum of 7 months vaccination schedule. Results: DC vaccinations were safe and tolerable. Nine (14%) of 64 patients are alive as of January 2010. Median survival was 17 (95% CI 12-26) months. Preliminary analysis of long-term immunological outcomes demonstrated the induction of long-lived melanoma-antigen specific CD8+T cells in a patient who obtained durable complete regression of in-transit melanoma. There, DC vaccination expanded circulating MART-1-specific CD8+ T cells. These could be detected after the fourth and eighth DC vaccination as well as 6 years after the last vaccination with DCs. The T cells had a predominantly effector memory phenotype. A broad repertoire of CD4+ T cells recognizing multiple tumor antigens was also induced in the same patient. These induced tumor-specific CD4+ T cells primarily secreted IL-2. Conclusions: DC vaccines can bring clinical benefit and elicit durable responses in a fraction of patients with metastatic cancer. DC vaccines have the potential to expand melanoma- antigen specific memory T cells. No significant financial relationships to disclose.
Failure of synoviocytes and cartilage body derived cells to form ectopic cartilage in vivo suggests critical involvement of the joint microenvironment in synovial chondromatosis
Authors: Rik Lories, Inge Derese, Patrick Verschueren, G Vanderlinden, Rene Westhovens, Frank Luyten
Journal: Annals of the Rheumatic Diseases (2004)
Safety analysis, correlation with response and previous treatments of the association of everolimus (EVE) and exemestane (EXE) in 181 metastatic breast cancer patients (MBC)
Authors: L. Moscetti, P. Vici, I. Sperduti, M. Palleschi, V. Magri, L. Iezzi, M.A. Fabbri, L. D'Onofrio, L. Mentuccia, A. Vaccaro, P. Trenta, S. Ramponi, C. Roma, E.M. Ruggeri
Journal: Annals of Oncology (2015)
Effect of clofarabine on lymphocyte populations in patients treated for solid tumors
Authors: C. Cunningham, J. Nemunaitis, N. Senzer, D. Richards, S. Vukelja, R. Abichandani, M. Vasconcelles
Journal: Journal of Clinical Oncology (2007)

21134 Background: Clofarabine (CLOLAR®) is a next-generation nucleoside analog designed as a hybrid molecule to improve the efficacy and minimize the extramedullary toxicity of other nucleoside analogs. Such analogs are known to have a variety of effects on both humoral and T-cell immune function. Fludarabine, the drug most closely related to clofarabine, causes major alterations in the CD4:CD8 lymphocyte ratios, associated with marked increases in the rate of opportunistic infections. In contrast, gemcitabine has a selective detrimental effect on the B-lymphocyte subset. Therefore, while conducting a phase I dose-finding trial of clofarabine in patients with solid tumors, we investigated its effects on lymphocyte sub-populations. Methods: A phase I dose-finding study is ongoing in patients with solid tumors who receive clofarabine once a week for 3 weeks every 28 days. Blood samples were collected from patients in the highest dose levels before, during, and after clofarabine administration for lymphocyte quantitation and phenotyping using flow cytometry. Results: Of the 11 patients who had samples collected, 5 currently have both baseline and postbaseline values available (1 at the 129 mg/m 2 dose level and 4 at the 103 mg/m 2 dose level). Overall, the percentage of T cells and CD8 suppressor cells did not decrease significantly with clofarabine administration. In 1 patient where data from 2 cycles were available, CD4 cells decreased slightly after the first cycle, suggesting a possible cumulative effect. However, in all 5 patients CD19 cells decreased significantly after the first infusion of clofarabine and remained suppressed for the duration of the study period. Conclusions: Although clofarabine is a purine analog (as is fludarabine), its effects on lymphocyte subsets more closely resemble gemcitabine, a pyrimidine analog. If substantiated, these findings should have bearing on future decisions about appropriate drug combinations involving clofarabine. No significant financial relationships to disclose.
Better utilization of neutropenic precautions and adherence to guidelines to improve cost effectiveness and patient convenience.
Authors: Ali Mehmood Raufi, Shada Attraplsi, Yehuda Z. Lebowicz
Journal: Journal of Clinical Oncology (2016)

227 Background: Cancer patient are generally immunocompromised and are at increased risk of infections once absolute neutrophils count is less than 500. The aim of the study to evaluate the inpatient utilization of a standardized neutropenic precautions in cancer patients admitted with febrile neutropenia. Methods: From Jan 2010 to May 2015, established cancer patients were included in this retrospective study who were admitted in Cabel Huntington hospital, Huntington, WV with a diagnosis of febrile neutropenia and were placed on Neutropenic precautions (NP). We analyzed if NP were discontinued once patient is stable and no longer neutropenic during hospital stay. Results: A total of 159 cancer patients with admitting diagnosis of febrile neutropenia were identified. 107 out of 159 (67%) patients had solid malignancies while 33% had hematologic malignancies. Median age was 61 (Range of 20-88 years). 69 patients were male while 90 patients were female. Median duration of Neutropenic precautions (NP) was 4 (Mean 5.69 and range: 1-35). NP were appropriately discontinued in 30% of patients during hospital stay however approximately 70% of patients continued to be on NP even after neutropenia resolved (48 vs 111 patients). Median duration of unnecessary NP was 3 with a mean of 3.87 and range of 1-18 days. Conclusions: Better utilization of Neutropenic precautions and adherence to guidelines will improve overall cost effectiveness as well as patient convenience by avoiding unnecessary restriction.
Junior doctors lose legal challenge over contract imposition
Authors: Clare Dyer
Journal: BMJ (2016)

The health secretary for England, Jeremy Hunt, has fought off a legal challenge by junior doctors who argued that he was acting unlawfully by forcing them to work under an unsafe new contract.

Justice for Health, a group of five junior doctors, argued at the High Court in London that Hunt was acting outside his legal powers when he made a statement to parliament in July 2016 announcing that he was imposing the contract after junior doctors in England voted against it.1

The group also contended that Hunt’s statements on the contract imposition were unclear, breaching his duty of transparency, and that he was acting irrationally in citing the proposed seven day NHS to justify the new contract.

But Mr Justice Green ruled in favour of the health secretary on all …
Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury
Authors: Yoon Kyung Choi, Takakuni Maki, Emiri T Mandeville, Seong-Ho Koh, Kazuhide Hayakawa, Ken Arai, Young-Myeong Kim, Michael J Whalen, Changhong Xing, Xiaoying Wang, Kyu-Won Kim, Eng H Lo
Journal: Nature Medicine (2016)
qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination
Authors: W. Jiang, C. Johnson, N. Simecek, M. R. López-Álvarez, D. Di, J. Trowsdale, J. A. Traherne
Journal: Genome Medicine (2016)

Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus. We used reference DNA samples to validate the accuracy and a cohort of 1698 individuals to evaluate capability for precise copy number discrimination. The method provides improved information and identifies KIR haplotype alterations that were not previously visible using other approaches.
Observational study on the long term cognitive and cardiac outcome after prenatal exposure to chemotherâpy in children 18 months or older
Authors: Frédéric Amant, Kristel Van Calsteren, MJ Halaska, GM Mhallem, Lieven Lagae, MA Willemsen, L Kapusta, Ben Van Calster, H Wouters, Lieve Heyns, S Han, Tomek, L Mertens, P Ottevanger
Journal: The Lancet Oncology (2012)
Elevated stem cell marker CD133 mRNA in peripheral blood predicts colon cancer recurrence
Authors: E. H. Lin, M. Hassan, Y. Li, H. Zhao, A. Nooka, K. Xie, R. Champlin, X. Wu, D. Li
Journal: Journal of Clinical Oncology (2007)

10504 Background: CD133 is a specific stem cell marker that enriches cancer stem cells of many tumor types including colon cancer as well as circulating endothelial progenitors (CEP). CEP is vital in postnatal angiogenesis and elevated CEP is a proven favoable prognositic marker for heart disease but a potentially poor prognostic marker for cancer. We examined whether elevated CD133 mRNA expression levels in peripheral blood mononuclear cells (PBMC) predict recurrence in colon cancer patients. Methods: We developed and validated a semi-quantitative real-time RT-PCR to quantify CD133 mRNA levels relative to GADPH mRNA. Sixty-six colon cancer patients were enrolled between February 2002 and December 2003. The protocol excluded patients with history of cardiac disease or surgery &lt; 4 weeks from the enrollment and were followed for recurrence for a median 30 months. A central statistician performed multivariate unconditional logistics regression analysis. Results: Among the patients without recurrence, 93% had a CD133 mRNA level &lt; 4.79, whereas 7% had a CD133 mRNA value ≥ 4.79 (p = 0.029). Among patients with a CD133 mRNA value ≥ 4.79, 85% had experienced recurrence compared to 15% of the patient who had no recurrence (p = 0.03). Elevated CD133 mRNA levels at a cut-off point ≥ 4.79 versus &lt; 4.79 were associated with an odd ratio of 22.6 for recurrence (95% CI, 1.7–291.2; p = 0.02); in comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8–164; p = 0.01) for stage IV patients versus stage I-III patients. No other predictive variables for recurrence were identified including age, race, sex, tumor differentiation, smoking, and diabetes etc. We also observed an trend of association with elevated carcinoma embryonic antigen (CEA) levels (p = 0.03, one sided) and a decreased survival (p = 0.035, one sided) with elevated CD133 mRNA level at a cutoff point ≥ 4.79. Conclusions: Elevated CD133 mRNA levels at a cutoff ≥ 4.79 in PBMC predict colon cancer recurrence independent of stage IV disease. The current assay has certain advantages over flow cytometry for wider clinical application. CD133+ cells measured by CD133 mRNA may contain both CEP and cancer stem cells, leading to increased risks of recurrence. No significant financial relationships to disclose.
IL-3 Specifies Early Hematopoietic Development from Human iPSCs and Synergizes with M-CSF and G-CSF on Myeloid Differentiation
Authors: Nico Lachmann, Mania Ackermann, Eileen Frenzel, Christine Happle, Olga Klimenkova, Sebastian Brennig, Doreen Lüttge, Theresa Buchegger, Sabina Janciauskiene, Julia Skokowa, Dagmar Dilloo, Thomas Moritz
Journal: Blood (2014)
Effects of Chronic Transfusion Therapy on MRI and MRA in Children with Sickle Cell Anemia at Risk for Primary Stroke: Baseline Imaging from the Twitch Trial
Authors: Kathleen J. Helton, Donna Roberts, William Herbert Schultz, Barry R. Davis, Theodosia A. Kalfa, Sara L. Pressel, Robert J. Adams, Russell E. Ware
Journal: Blood (2014)
P1.33: Afatinib Versus Chemotherapy for EGFR Mutation-Positive NSCLC Patients Aged ≥65 Years: Subgroup Analysis of LUX-Lung 3/6
Authors: Luis Fein, Yi-Long Wu, Lecia V. Sequist, Sarayut L. Geater, Sergey Orlov, Ki Hyeong Lee, Chun-Ming Tsai, Terufumi Kato, Katsuyuki Kiura, Carlos H. Barrios, Martin Schuler, Vera Hirsh, Nobuyuki Yamamoto, Kenneth O’Byrne, Tony Mok, Dan Massey, Angela Märten, James Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2016)
Correction: Functional screen identifies regulators of murine hematopoietic stem cell repopulation
Authors: Per Holmfeldt, Miguel Ganuza, Himangi Marathe, Bing He, Trent Hall, Guolian Kang, Joseph Moen, Jennifer Pardieck, Angelica C. Saulsberry, Alba Cico, Ludovic Gaut, Daniel McGoldrick, David Finkelstein, Kai Tan, Shannon McKinney-Freeman
Journal: The Journal of Experimental Medicine (2016)

Vol. 213, No. 3, March 7, 2016. Pages [433–449][1].

The authors regret that in their original paper, the gene Zfp521 appeared as Zfp251 . The online HTML and PDF versions of this article have been corrected. Figs. 1, 3, and 5 have also been edited to correct this mistake. The error only remains
Antibiotic Prophylaxis for Cesarean Delivery — When Broader Is Better
Authors: Robert A. Weinstein, Kenneth M. Boyer
Journal: New England Journal of Medicine (2016)

Approximately 4 million babies are born each year in the United States. Of these infants, about a third are delivered by cesarean section. One of the many concerns about cesarean deliveries is the high risk of maternal infectious complications, which are 5 to 10 times more frequent than with vaginal deliveries.1 During cesarean delivery, the endometrial cavity and operative field may be seeded with pathogens, carried from the birth canal or the skin, that put mothers at risk for endometritis (incidence without prophylaxis, 4 to 18%) and of surgical-site infections (incidence without prophylaxis, 7 to 10%).2 To reduce these risks, . . .
Disruption of the Hexb/Enc-1 Antisense Gene and Identification of Elevated Enc-1 Expression in Patients with Hairy Cell Leukemia.
Authors: Mikael Lerner, Marianne Hammarsund, Olle Sangfelt, Chaoyong Zhu, Mats Merup, Monika Jansson, Goesta Gahrton, Hanneke Kluin-Nelemans, Stefan Einhorn, Dan Grander, Martin Corcoran
Journal: Blood (2004)
Use of Third Party Ancillary Cells for Enhancement of Full Donor Chimerism and Immunomodulation in Cord Blood Transplants.
Authors: Manuel N. Fernandez, Jose R. Cabrera, Carmen Regidor, Guiomar Bautista, Emilio Ojeda, Rafael Fores, Isabel Sanjuan, Elena Ruiz, Santiago Gil, Rosa Gonzalo, Isabel Millan, Isabel Krsnik, Belen Navarro, Jose A. Garcia-Marco
Journal: Blood (2007)
P0898 : TD-6450, A next generation once-daily NS5A inhibitor, has potent antiviral activity following a 3-day monotherapy study in genotype 1 HCV infection
Authors: E. Lawitz, M. Rodriguez-Torres, R. Kohler, A. Amrite, C. Barnes, M.L.C. Pecoraro, J. Budman, M. McKinnell, C.B. Washington
Journal: Journal of Hepatology (2015)
XPO1 is selinexor prime target: validation by mutating cysteine 528 on both XPO1 alleles using CRISPR/Cas9 genome editing
Authors: Jasper Neggers, Thomas Vercruysse, Maarten Jacquemyn, Els Vanstreels, Erkan Baloglu, Sharon Shacham, Marsha Crochiere, William Senapedis, Yosef Landesman, Dirk Daelemans
Journal: Cancer Research (2015)
Characteristics and outcomes of patients receiving chemotherapy in a cancer center ICU: A 5 year retrospective
Authors: N. D. Raoof, M. Knott, S. M. Pastores, L. P. Voigt, N. A. Halpern
Journal: Journal of Clinical Oncology (2006)

6134 Background: Administration of chemotherapy is traditionally guided by functional status, and chemotherapy is commonly withheld from very sick people. In our ICU, we observed that we customarily administered chemotherapy to patients in multisystem organ failure. Very little has been published in the literature on this topic, therefore we sought to characterize patients who received chemotherapy during their intensive care unit (ICU) admission in a cancer hospital over a 5-year period. Methods: We evaluated all ICU admissions receiving chemotherapy between October 1998 and September 2003. If patients had multiple admissions, only the first was included. We analyzed age, gender, MPM-II scores, and ICU and hospital length of stay (LOS). Additionally, we identified patients who were on mechanical ventilation, vasopressors or were treated with renal replacement therapy at the initiation of chemotherapy. Mortality at ICU discharge, hospital discharge, and at 6 months and one year post hospital discharge were also determined. Results: During the study period, 4.2% (111/2,645) of all ICU admissions received chemotherapy, averaging 22.2 administrations per year. Only first admissions (a total of 103 patients; 60 men and 43 women) were analyzed. Average age was 51.4 years, with an MPM-II score of 53%, an ICU LOS of 9.1 days and a hospital LOS of 30.6 days. Although over a third of patients were on mechanical ventilation when chemotherapy was initiated, ICU mortality was only 23%. In contrast, all in hospital mortality was 46%. ( Table ) Conclusions: Most patients were critically ill when chemotherapy was administered but survived to ICU discharge. However, only 24% of patients were alive at one year. Whether chemotherapy should be considered a useful component of ICU care for cancer patients requires further study. [Table: see text] No significant financial relationships to disclose.
P0687 : Regulation of hepcidin (HAMP) as driving force for macrophage-mediated hepatitis C (HCV) persistency
Authors: P. Foka, A. Dimitriadis, E. Karamichali, E. Kyratzopoulou, D. Giannimaras, J. Koskinas, A. Mamalaki, U. Georgopoulou
Journal: Journal of Hepatology (2015)
Gemcitabine, Dexamethasone, Cisplatin (GDP) Compared to Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Prior to Autologous Stem Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: Final Results of the Randomized Phase III NCIC CTG Study LY12
Authors: Michael Crump, John Kuruvilla, Stephen Couban, David Macdonald, Vishal Kukreti, C. Tom Kouroukis, Ralph M. Meyer, Morel Rubinger, Rena Buckstein, Kevin R Imrie, Massimo Federico, Nicola Di Renzo, Kang Howson-Jan, Tara Baetz, Leonard Kaizer, Michael Voralia, Harold J. Olney, A. Robert Turner, Jonathan Sussman, Annette E Hay, Marina Djurfeldt, Bingshu E Chen, Lois Shepherd
Journal: Blood (2012)
Unsupervised cluster analysis of sputum cytokine profiles in a large asthma patient cohort
Authors: Sven Seys, Hans Scheers, Gudrun Marijsse, Ellen Dilissen, Gon Van den Bergh, Pieter Goeminne, Paul Van den Brande, Jan Ceuppens, Lieven Dupont, Dominique Bullens
Journal: Allergy (2014)