tbuckley/cabot-search huggingface dataset:
Utilization of positron emission tomography scans (PET) in the management of NSCLC at a center with limited access to this imaging modality
Authors: B. P. Nair, A. M. Safar
Journal: Journal of Clinical Oncology (2006)

6140 Background: PET is recommended as an important diagnostic aid in the initial evaluation of patients with lung cancer, according to the NCCN guidelines. The aim of this study is to estimate the proportion of NSCLC patients receiving PET, its impact on staging, and its utilization by different treating specialties, in a facility with limited access to PET. This is a situation comparable to several community medical centers. This study was done at the Veterans Hospital, Little Rock (VALR), where the requested PET scans were done at an outside facility, due to its unavailability within this center. Methods: All patients with NSCLC who were diagnosed or treated at VALR between 01/01/03 and 06/30/05 were retrospectively identified from the tumor registry, and details of PET were obtained. Subsequently electronic patient records at VALR were reviewed and the best estimate of pre-PET and post-PET stage was made. The details of the requesting specialty were also obtained. Then frequency distributions relevant to the aims of the study were calculated. Results: 444 patients with diagnosis of NSCLC were identified in this time period, of which 48 (10.8%) had PET scans. Overall 10 (21%) patients were down staged and 4 (8.3%) patients were upstaged. PET helped establish stage among 13 of 15 patients with unknown stage. Details are provided in the table . The number of PET scans requested by treating specialties are as follows: medical oncology 44% (21), pulmonary 40% (19), cardiothoracic surgery 13% (6), and others 3% (2). Conclusions: In this study 10.8% of patients with NSCLC had PET. There was establishment of, or change in stage among 27 (56%) patients. These numbers are comparable to studies from larger centers with ready availability to PET, reflecting its adequate utilization in this setting with limited access. Medical oncology and pulmonary services initiated majority of the PET requests, possibly because of their involvement in the early diagnostic work-up in this patient population. [Table: see text] No significant financial relationships to disclose.
Incidence and Implications of Aborted Myocardial Infarction in STREAM
Authors: Neda Dianati-Maleki, Frans Van de Werf, Patrick Goldstein, Jennifer Adgey, Yves Lambert, Vitaly Sulimov, Fernando Rosell-Ortiz, Anthony H Gershlick, Yinggan Zheng, Paul W Armstrong
Journal: Circulation (2013)
Characteristics of Extensive Stage Small Cell Lung Cancer: A National Cancer Database Review.
Authors: Jessica Gries, Brody Slostad, Apar Kishor Ganti, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2015)

e17590 Background: Race and insurance status are socio-demographic characteristics that influence extensive stage (Stage IV) lung cancer incidence (Halpern MT, et al. (2008) Association of insurance status and ethnicity with cancer stage at diagnosis for 12 cancer sites: a retrospective analysis. Lancet Oncol 9:222-232.). This is the largest study looking at small cell lung cancer (SCLC) to determine epidemiological patient features associated with extensive stage disease. Methods: A population-based study using the National Cancer Database (2000-2012), which contains 70% of all cancer diagnoses in the U.S. from 1658 American College of Surgeons Accredited-Hospitals. SCLC presenting with extensive stage was compared to the entire cohort of SCLC patients using the Chi square test. Results: Of all SCLC patients (N=532,542), 55% were extensive stage at diagnosis. Extensive stage at presentation was higher in uninsured (62%) vs. private insurance (54%) patients. More men (58%) had extensive stage at diagnosis than women (52%). Minimal changes were seen across incomes, comorbidities and distances traveled (Table). Conclusions: This is the first and largest study to determine how several demographic variables affect extensive stage SCLC presentation. Uninsured and male patients present more frequently than privately insured and female patients with extensive stage disease, respectively. Additionally, similar to a previous NCDB study, this study, which includes 5 times as many lung cancer patients as the previous study, shows uninsured and Medicaid patients present with more extensive stage disease (Halpern MT, et al. (2008) Association of insurance status and ethnicity with cancer stage at diagnosis for 12 cancer sites: a retrospective analysis. Lancet Oncol 9:222-232.). Extensive Stage SCLC *=p<.001, **=p<.01, ***=p<.05 % Extensive Stage Race/ Ethnicity** Hispanic 57 White 55 Black 54 Gender* Male 58 Female 52 Distance Traveled* (miles) <5 56 5 to 9 56 10 to 24 55 25 to 49 54 50 to 99 54 >=100 55 Insurance* None 62 Medicaid 59 Other Gov't 58 Medicare 55 Private 54 Household Income***(per year) < $36,000 55 $36,000 - 43,999 55 $44,000 - 52,999 55 $53,000 - 68,999 55 > $69,000 56 Comorbidity* 2+ 58 One 57 None 55 Age* 40-49 55 50-59 57 60-69 56 70-79 54 80-89 54 Overall % Extensive Stage 55
Liver-Resident Memory CD8 + T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection
Authors: Daniel Fernandez-Ruiz, Wei Yi Ng, Lauren E. Holz, Joel Z. Ma, Ali Zaid, Yik Chun Wong, Lei Shong Lau, Vanessa Mollard, Anton Cozijnsen, Nicholas Collins, Jessica Li, Gayle M. Davey, Yu Kato, Sapna Devi, Roghieh Skandari, Michael Pauley, Jonathan H. Manton, Dale I. Godfrey, Asolina Braun, Szun Szun Tay, Peck Szee Tan, David G. Bowen, Friedrich Koch-Nolte, Björn Rissiek, Francis R. Carbone, Brendan S. Crabb, Mireille Lahoud, Ian A. Cockburn, Scott N. Mueller, Patrick Bertolino, Geoffrey I. McFadden, Irina Caminschi, William R. Heath
Journal: Immunity (2016)
UK must stop arms sales to Saudi Arabia in light of bombings of Yemeni health facilities, says charity
Authors: Jacqui Thornton
Journal: BMJ (2016)

The charity Medact has called on the UK international trade secretary, Liam Fox, to suspend arms sales to Saudi Arabia to prevent further bombing of healthcare facilities in the conflict in Yemen. Fox, who studied medicine in Glasgow and worked as a GP in Buckinghamshire before entering politics, is now responsible for licensing arms sales in his ministerial role.

Campaigners from Medact, a charity for health professionals focused on global health improvement, and other doctors and health professionals have appealed to Fox as a doctor to think of the health of Yemeni people, the brutal attacks on clinicians, and his duty to “first do no harm.” They cited evidence that British arms were being used to …
Multiplexed genotyping using a novel digitally inscribed bead-based system
Authors: S. M. Lipkin, J. Yeakley, E. Chao, J. Velasquez, M. Lopez, J. Rhee, T. McDaniel, I. Lewis, H. Chen
Journal: Journal of Clinical Oncology (2007)

21089 Background: Genotyping of clinical samples has been limited to low levels of multiplexing, ranging from one to a few dozen single nucleotide polymorphisms (SNPs) per sample. By increasing multiplexing levels, a clinical lab can increase information content per sample, decreasing costs and sample material requirements. Methods: We have adapted the GoldenGate® Assay for simultaneously genotyping 96 to 1,536 SNPs to the BeadXpress™ System, a new high-throughput platform that utilizes digitally inscribed VeraCode™ beads in a compact fluidic instrument. Genotyping on this platform ranges from 96 to 384 multiplexing, using the same GoldenGate Assay that has proven highly robust for millions of genotypes. In preliminary tests, we have observed greater than 99% call rates, and greater than 99.5% rates for reproducibility and heritability. In a test of 96 SNP genotypes chosen for a study of colorectal cancer, a point mutation in the MSH2 gene, previously implicated in predisposition to several cancers, was correctly genotyped when compared to qPCR analysis of the same samples. Conclusion: Together with genotyping data from reference samples, the GoldenGate Assay on the BeadXpress System has yielded highly reproducible and accurate genotypes, suggesting that this approach will prove useful for rapid refinement of SNPs for development of clinical genotyping tests. No significant financial relationships to disclose.
Prospective observational study for the impact of short-term periodic intravenous steroid premedication for gastrointestinal cancer chemotherapy on bone metabolism.
Authors: Atsushi Ishiguro, Michio Nakamura, Tetsuhito Muranaka, Satoshi Yuki, Taichi Murai, Chika Matsuda, Ayane Oba, Kazufumi Itaya, Taku Shigesawa, Yuta Koike, Yomo Fujita, Ayana Endo, Yoko Tsukuda, Yuji Ono, Takahiko Kudo, Atsushi Nagasaka, Shuji Nishikawa, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2016)

523 Background: Although intravenous glucocorticoid (GC) premedication (GCP) before chemotherapy (CTx) are frequently used to prevent nausea and vomiting for continuing comfortable CTx, the side effects of intermittent GCs on bone health have not yet been reported. So we designed a multicenter, prospective, observational study to evaluate the impact of periodic GCP on bone metabolism in gastrointestinal cancer (GIC) patients (pts). Methods: The eligibility criteria were as the follows: (i) histologically proven GIC. ; (ii) The duration of periodical GCP is weekly, biweekly, and triweekly. More over 4 weeks GC free intervals is not permissible. ; (iii) age over 20. The primary endpoint was to investigate the variations of bone mineral densities (BMD) at lumbar spine measured by dual energy x-ray absorptiometry (DEXA) and bone turnover biomarkers, cross-linked N-telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP), between baseline (BL) and 16 weeks after starting CTx (16w). Results: From June 2013 to April 2015, 98 pts were enrolled. Two pts were not proven as GIC histologically. One patient (pt) was not measured on baseline DEXA. One pt was taken bisphosphonates already on BL point. Four pts were not administered CTx or GCP, and 16 pts were not measured BMD on 16w due to several reasons such as pts refusal, discontinuation of CTx, death and so on (74 pts were full analysis set). In 55 pts (74.3 % of FAS), the levels of BMD at 16w were decreased compared with BL and the average amount of BMD reduction rate was 5.83 % (-38.8 % to 31.1 %). Although no significant difference was found in the level of NTX between BL and 16w (p = 0.118), there was the significant increase of BAP level statistically (p = 0.006). There were also significant correlations between percent change in BMD and NTX, BMD and BAP, NTX and BAP (p = 0.037, 0.029, and 0.003, respectively). Conclusions: We found that periodic GCP in GIC pts caused the reduction of BMD and some influences for bone turnover. These results indicate that GCP might generate more serious osteoporosis of GIC pts during CTx. Further studies are necessary to illustrate the need to prevent GC induced osteoporosis in using GCP. Clinical trial information: 000011054.
First-line chemoimmunotherapy in metastatic breast carcinoma: Effect of a combination of paclitaxel and LAG-3-ig (IMP321), a novel MHC class II agonist, on T-cell responses and antitumor activity.
Authors: M. Gutierrez, C. Brignone, F. Mefti, F. Triebel
Journal: Journal of Clinical Oncology (2010)

2513 Background: IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then CD8+ T cell activation. We report clinical and biological results of a phase Ib trial in patients with metastatic breast carcinoma (MBC) receiving first-line paclitaxel weekly 3 weeks out of 4. Methods: MBC patients were administered one dose IMP321 s.c. every two weeks for a total of 24 weeks (12 injections). The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8, and D15, for 6 cycles). Blood samples were assayed 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC activation and long-lived CD8 T-cell responses and to detect any human anti-IMP321 antibody formation. Results: Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25, and 6.25 mg). No clinically significant adverse events were observed. IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of long-lived effector-memory CD8 T cells. Clinical benefit was observed for 90 % of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50 % compared favorably to the 25% rate reported in the historical control group (p=0.005). Conclusions: The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immutep Immutep
Pharmacokinetic and Pharmacodynamic Modeling of the Relationship Between TAK-442 Exposure and Clinical Outcome In Patients Undergoing Elective Knee Arthroplasty
Authors: Fran Stringer, Bart Ploeger, Nolan Wood, Patrick Moneuse, Masaki Kawamura, Stuart Kupfer, Jeff Spaeder, Graham Scott
Journal: Blood (2010)
Hypoplasia of the transverse aortic arch as a mechanism for late aneurysm formation at the site of Dacron patch angioplasty for coarctation of the aorta
Authors: Jan Bogaert, Frank Rademakers, Marc Gewillig, Johny Verschakelen, M Vanhove, M Dumoulin, Willem Daenen, Albert Baert
Journal: Circulation (1994)
Dietary Fat and Risk of Cardiovascular Disease: Recent Controversies and Advances
Authors: Dong D. Wang, Frank B. Hu
Journal: Annual Review of Nutrition (2017)

Health effects of dietary fats have been extensively studied for decades. However, controversies exist on the effects of various types of fatty acids, especially saturated fatty acid (SFA), on cardiovascular disease (CVD). Current evidence supports that different types of dietary fatty acids have divergent effects on CVD risk, and the effects also depend strongly on the comparison or replacement macronutrient. A significant reduction in CVD risk can be achieved if SFAs are replaced by unsaturated fats, especially polyunsaturated fatty acids. Intake of industrially produced trans fat is consistently associated with higher CVD risk. Both n-6 and n-3 polyunsaturated fatty acids are associated with lower CVD risk, although the effects of fish oil supplementation remains inconsistent. The 2015–2020 Dietary Guidelines for Americans place greater emphasis on types of dietary fat than total amount of dietary fat and recommend replacing SFAs with unsaturated fats, especially polyunsaturated fatty acids for CVD prevention.
Midostaurin in Combination with Intensive Induction and As Single Agent Maintenance Therapy after Consolidation Therapy with Allogeneic Hematopoietic Stem Cell Transplantation or High-Dose Cytarabine (NCT01477606)
Authors: Richard Schlenk, Konstanze Döhner, Helmut Salih, Andrea Kündgen, Walter Fiedler, Hans-Juergen Salwender, Joerg Westermann, Katharina S. Götze, Heinz-August Horst, Gerald Wulf, Michael Lübbert, Doris Kraemer, Thomas Kindler, Mark Ringhoffer, Peter Brossart, Gerhard Held, Richard Greil, Thomas Südhoff, Anja Münnich, Daniela Weber, Verena I. Gaidzik, Maria-Veronica Teleanu, Peter Paschka, Frauke Theis, Michael Heuser, Felicitas Thol, Axel Benner, Arnold Ganser, Hartmut Döhner
Journal: Blood (2015)
Cancer Drugs Fund requires further reform
Authors: Richard Grieve, Keith Abrams, Karl Claxton, Ben Goldacre, Nicholas James, Jon Nicholl, Mahesh Parmar, Chris Parker, Jasjeet S Sekhon, Liam Smeeth, David Spiegelhalter, Mark Sculpher
Journal: BMJ (2016)

Reliance on “real world” observational data undermines evidence base for clinical practice

The reforms to the Cancer Drugs Fund implemented in July were an excellent opportunity to generate evidence on the effectiveness of new cancer drugs.1 Unlike under the previous arrangements, data on patients’ outcomes will have to be collected for all drugs funded by the scheme. However, the reforms’ stated reliance on “real world” (observational) data will not generate reliable evidence of effectiveness. We propose an alternative model, using timely randomised controlled trials within routinely collected data sources, to establish which drugs are relatively effective. The current arrangement encourages early access to drugs, with high prices but uncertain benefits, whereas our proposal will provide high quality evidence for future decisions and therefore larger gains in population health.

The Cancer Drugs Fund was introduced in England in 2010-11 with a £50m (€58m; $65m) budget, which grew to £340m in 2015-16 without evidence of patient benefits.2 Since the reforms, the National Institute for Health and Care Excellence (NICE) is responsible for appraising all new cancer drugs, and the fund will pay for those drugs which have a chance of being judged cost effective, …
Phase III randomized study of second line ADI-peg 20 (A) plus best supportive care versus placebo (P) plus best supportive care in patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Ghassan K. Abou-Alfa, Shukui Qin, Baek-Yeol Ryoo, Sheng-Nan Lu, Chia-Jui Yen, Yin-Hsun Feng, Ho Yeong Lim, Francesco Izzo, Massimo Colombo, Debashis Sarker, Luigi Bolondi, Gina M. Vaccaro, William Proctor Harris, Zhendong Chen, Richard Hubner, Tim Meyer, John S. Bomalaski, ChenChun Lin, Yee Chao, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2016)

4017 Background: Arginine (Ar) depletion is a putative target in HCC, which lacks the citrulline (Ci) to Ar repleting enzyme argininosuccinate synthetase. A is an Ar degrading enzyme cloned from M. hominis and produced in E. coli and conjugated with polyethylene glycol. Methods: Pts with histologically proven advanced HCC and Child-Pugh (CP) up to B7 who failed or were intolerant to prior systemic therapy, were 2:1 randomized to A 18 mg/m2vs P IM injection weekly. The study was stratified by the combination of geographic region (Asia vs Other) and prior treatment status (sorafenib (S) vs other (O) failure). The primary endpoint was overall survival (OS) with secondary endpoints progression-free survival (PFS), safety and Ar and Ci levels correlatives. The study was planned for 422 A and 211 P, with 93% power to detect a 1.6 months (m) increase in median OS (4 to 5.6 m; 1-sided α = 0.025). Results: 635 pts were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 13% alcohol and 7% NASH, 76% stage IV and 30% vascular invasion, CP A 90.6%, 70% progressed on S, 11.2% on O and 18.8% did not tolerate either. The mean number of doses was 14 for A and 17 for P. Median OS was 7.8 m for A vs 7.4 for P (p = 0.884, HR=1.022 (95% CI: 0.847, 1.233)) and median PFS 2.6 vs 2.6 (p = 0.075, HR=1.175 (95% CI: 0.964, 1.432)). The most common grade 3 and above AEs in both groups were fatigue (A: 1.9% and P: 3.3%), and decreased appetite (A: 1.9%, and P: 1.4%). Hypersensitivity reactions including anaphylaxis occurred in 2.1% pts on A. There were 15% deaths on A arm within 30 days of last dose vs 10.4% on P (progressive disease 83%, GI hemorrhage 8%, unknown/other 9%) Pts with Ar depletion for >8 weeks had a median OS of 12.3 m compared to 7.3 m (P = 0.0032) for ≤ 4 weeks. Similarly, pts with Ci increase for >8 weeks had a median OS of 11.6 m, compared to 3.5 m (P<0.0001) for ≤4 weeks. Conclusions: A did not demonstrate an OS benefit in the population of advanced HCC with failed prior systemic therapy. A was well tolerated. An OS benefit associated with prolonged Ar depletion was noted. Strategies to enhance prolonged arginine depletion and/or synergize the effect of A are underway Clinical trial information: NCT01287585.
Characterization of the Molecular Interplay Between HOXA9 and Ogt in Leukemia
Authors: Jean-Francois M Rual, Tao Xu, Cailin Collins, Honglai Zhang, Jingya Wang, Rork Kuick, Joel Bronstein, Venkatesha Basrur, Sung Soo Park, Kim Ha, Lili Chen, Kojo S.J. Elenitoba-Johnson, Andrew G. Muntean, Jay L. Hess
Journal: Blood (2014)
Testicular cancer: Fortieth anniversary of a cancer cure.
Authors: Peter Boyle, Cécile Pizot, Helen Jane Boyle
Journal: Journal of Clinical Oncology (2015)

e15555 Background: Patients with testicular cancer frequently present with disseminated disease. In 40 years the disease moved from being incurable to being one of the few forms of cancer where cure is possible. The impact of advances in therapy on mortality rates from testis cancer is quantified. Methods: Using mortality data from the World Health Organisation Mortality Database, temporal trends in the mortality rate from testicular cancer have been analysed. Age-adjusted rates per 100,000 have been calculated using the World Standard Population as the reference population. Results: Despite increases in incidence rates, mortality from testis cancer has been declining in all countries. The mortality rates in Central Europe had not changed much compared to Western Europe, but this situation has been changing since the mid-1990’s when platinum-based treatment regimens became widely available. In the former Federal Republic of Germany, mortality started to fall after 1978 while no change was evident in the former German Democratic Republic. After reunification, the mortality rate in the eastern part of Germany rapidly fell to the same level as in the western part. The establishment of specialist, multi-disciplinary treatment centres also contributed to the declines in mortality. Globally, it appears that over 300,000 patients with testicular cancer have been cured. Lawrence Einhorn, a Medical Oncologist, and John Donohue, a Urological Surgeon, at the University of Indiana, began a series of studies that resulted in the cure rate of metastatic testicular cancer increasing from 10% to 60% by 1978 through the use of a combination of cis-platinum, vinblastine, and bleomycin. In the mid-1970s, the chapter in a major cancer textbook note that “responses to chemotherapy are often transitory and it is doubtful if life is always prolonged in responders”. Conclusions: Progress against testicular cancer has been remarkable: five-year survival increased from around 10% in the 1970s to over 90% today. Much of this improvement is attributable to the development of chemotherapy regimens based on cis-platinum as well as a realisation of the importance of combined management of patients. The cure of testicular cancer represents one of the major advances in cancer treatment.
Retrieval of a migrated stent during endoscopic ultrasound-guided drainage of duodenal diverticular abscess
Authors: Sho Kitagawa, Keiya Okamura, Daiki Oku, Ai Minoura
Journal: Endoscopy (2016)

Endoscopic ultrasound (EUS)-guided drainage for an abdominal abscess has become recognized as a minimally invasive alternative to surgery. With regard to EUS-guided drainage of a pancreatic pseudocyst, the occurrence of stent migration into the pseudocyst is a relatively rare complication [1] and can be prevented by using double-pigtail stents [2]. This report describes endoscopic retrieval of a migrated double-pigtail stent during EUS-guided drainage of duodenal diverticular abscess.
Aspirin Induces Apoptosis in Human Leukemia Cells Independently of NF-κB and MAPKs through Alteration of the Mcl-1/Noxa Balance.
Authors: Ana M Cosialls, Daniel Iglesias-Serret, Maria Piqué, Montserrat Barragán, Antonio F Santidrián, Diana M González-Gironès, Llorenç Coll-Mulet, Mercè de Frias, Alberto Fernandez de Sevilla, Gabriel Pons, Joan Gil
Journal: Blood (2009)
Analyses of chromosomal abnormalities involving the MLT/MALT1 gene in marginal zone B-cell lymphoma using a novel interphase FISH assay
Authors: EM Penas Murgas, K Hinz, K Roser, C Copie-Bergman, Iwona Wlodarska, G Schilling, Peter Marynen, Anne Hagemeijer-Hausman, P Gaulard, T Loning, R Parwaresch, DK Hossfeld, J Dierlamm
Journal: Blood (2003)