bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Blood Loss After Transfemoral Amputations Is Twice the Intraoperative Loss: An Observational Cohort Study of 81 Nontraumatic Amputations
Authors: Wied Christian , Tengberg Peter T. , Kristensen Morten T. , Holm Gitte , Kallemose Thomas , Troelsen Anders , Foss Nicolai B. 
Published: May 2017

Introduction: Underestimation of the actual blood loss in patients undergoing nontraumatic transfemoral amputation (TFA) can impact negatively on outcome in these often frail patients, with very limited physiological reserves. The primary aim of this study is to estimate the total blood loss (TBL) after TFA, and second, to evaluate the impact of blood loss on 30-day mortality and medical complications. Methods: A single-center retrospective cohort study conducted from 2013 to 2015. The TBL was calculated on the fourth postoperative day. It was based on the hemoglobin levels, transfusions, and the estimated blood volume. Results: Eighty-one patients undergoing TFA were included for final analysis. The median TBL was 964 mL (interquartile range [IQR]: 443-1558). The intraoperative blood loss (OBL) was 400 mL (IQR: 200-500). The median difference between TBL and OBL was 688 mL (IQR: 124-1075). The patient received red blood cell (RBC) transfusion of a median amount of 2 units. Higher number of transfusions (>2) did not impact the outcome. From multivariable analysis, it was evident that the TBL increased significantly in patients with renal disease prior to surgery, ( P = .034). The TBL itself was not independently associated with increased 30-day mortality or medical complications. Conclusion: The TBL after TFAs is significantly greater than the volume estimated intraoperatively and increases significantly in the presence of renal disease prior to surgery. An increased TBL and requirement for RBC transfusion is not directly associated with 30-day mortality or medical complications. A high vigilance for anemia seems advisable when planning for TFA surgery. Research on optimum blood conservation and transfusion strategies during TFA is warranted.
Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell analysis
Authors: Smith Catherine C. , Paguirigan Amy , Jeschke Grace R. , Lin Kimberly C. , Massi Evan , Tarver Theodore , Chin Chen-Shan , Asthana Saurabh , Olshen Adam , Travers Kevin J. , Wang Susana , Levis Mark J. , Perl Alexander E. , Radich Jerald P. , Shah Neil P. 
Published: May 2017

Key Points
Polyclonal mechanisms of resistance, demonstrated by single-cell analysis, occur in the majority of AML patients who relapse on quizartinib.
Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival of megakaryocyte progenitors
Authors: Draper Julia E. , Sroczynska Patrycja , Leong Hui Sun , Fadlullah Muhammad Z. H. , Miller Crispin , Kouskoff Valerie , Lacaud Georges 
Published: May 2017

Key Points
Absence of RUNX1C in knock-in adult mice causes defective megakaryopoiesis and thrombocytopenia. Unlike total RUNX1 deficiency absence of RUNX1C does not alter megakaryocyte maturation but increases apoptosis in megakaryocyte progenitors.
Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma
Authors: Zinzani Pier Luigi , Ribrag Vincent , Moskowitz Craig H. , Michot Jean-Marie , Kuruvilla John , Balakumaran Arun , Zhang Yayan , Chlosta Sabine , Shipp Margaret A. , Armand Philippe 
Published: May 2017

Key Points
Treatment options for relapsed/refractory PMBCL are limited, and prognosis is generally poor. Pembrolizumab had a manageable safety profile and promising antitumor activity in heavily pretreated rrPMBCL patients.
An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease
Authors: Martin Paul J. , Storer Barry E. , Inamoto Yoshihiro , Flowers Mary E. D. , Carpenter Paul A. , Pidala Joseph , Palmer Jeanne , Arora Mukta , Jagasia Madan , Arai Sally , Cutler Corey S. , Lee Stephanie J. 
Published: May 2017

Key Points
Complete or partial response at 1 year without secondary systemic treatment provides clinical benefit in patients with chronic GVHD. Success defined by this endpoint is currently observed in fewer than 20% of patients after initial systemic treatment of chronic GVHD.
Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study
Authors: Yamada Hirotsugu , Tanaka Atsushi , Kusunose Kenya , Amano Rie , Matsuhisa Munehide , Daida Hiroyuki , Ito Masaaki , Tsutsui Hiroyuki , Nanasato Mamoru , Kamiya Haruo , Bando Yasuko K. , Odawara Masato , Yoshida Hisako , Murohara Toyoaki , Sata Masataka , Node Koichi ,   for the PROLOGUE Study Investigators
Published: May 2017

Abstract
Background
Diabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy. It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function. However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern. We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study.

Methods
Patients in the PROLOGUE study were assigned randomly to either add-on sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients in the overall study, 115 patients (55 in the sitagliptin group and 60 in the conventional group) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included in this study. The primary endpoint of this post hoc sub-analysis was a comparison of the changes in the ratio of E to e′ (E/e′) between the two groups from baseline to 24 months.

Results
The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group (−0.18 ± 0.55 vs. 1.91 ± 0.53, p = 0.008), irrespective of a higher E/e′ value at baseline in the sitagliptin group. In analysis of covariance, sitagliptin treatment was significantly associated with change in E/e′ over 24 months (β = −9.959, p = 0.001), independent of other clinical variables at baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in other clinical variables including blood pressure and glycemic parameters, and echocardiographic parameters, such as cardiac structure and systolic function, were comparable between the two groups. There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period.

Conclusions
Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e′) independent of other clinical variables such as blood pressure and glycemic control.
Trial registration UMIN000004490 (University Hospital Medical Information Network Clinical Trials). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356; registered November 1, 2010
RETRACTED ARTICLE: A new application of boundary integral behaviors of harmonic functions to the least harmonic majorant
Authors: Han Minghua , Sun Jianguo , Xue Gaoying 
Published: May 2017

AbstractOur main aim in this paper is to obtain a new type of boundary integral behaviors of harmonic functions in a smooth cone. As an application, the least harmonic majorant of a nonnegative subharmonic function is also given.
Aggressive care at the end-of-life for younger patients with cancer: Impact of ASCO's Choosing Wisely campaign.
Authors: Chen Ronald C. , Falchook Aaron David , Tian Fang , Basak Ramsankar , Hanson Laura , Selvam Nandini , Dusetzina Stacie 
Published: May 2017

LBA10033 Background: Aggressive medical care at the end of life is widely recognized to be harmful to cancer patients. This includes cancer-directed procedures and therapies; emergency room and ICU admissions; and in-hospital deaths. Prevalence of its use in patients younger than 65 has not been previously examined. We evaluated use of aggressive care within the last 30 days of life from before to after ASCO’s 2012 Choosing Wisely campaign aimed at reducing aggressive end-of-life care. Methods: Claims data from the HealthCore Integrated Research Database were analyzed, which overall includes ~60 million individuals enrolled in Blue Cross and/or Blue Shield licensed plans across 14 states. Patients aged ≤ 65 who died between 2007-2014 and who had diagnoses for metastatic lung, colorectal, breast, pancreatic, and prostate cancers were included. Poisson multivariable regression models assessed the associations between age group, geographic region, gender, and regional education and income measures with aggressive care. Results: 28,731 patients were analyzed. 71-76% of patients across different cancers received aggressive care within the last 30 days of life (Table), including 30-35% of patients who died in the hospital. Rates of aggressive care use between early 2012 before Choosing Wisely vs. 2014 were unchanged in patients with colorectal and breast cancers; and increased in lung, pancreatic and prostate cancers. On the other hand, hospice use ranged from 14-18% across cancers. Multivariable models showed regional variations in aggressive care and hospice use. Conclusions: There is substantial overuse of aggressive end-of-life care among younger patients with incurable cancers. Aggressive care did not decrease following the 2012 ASCO Choosing Wisely recommendations. [Table: see text]
Targeted therapy for advanced solid tumors based on molecular profiles: Early results from MyPathway, an open-label, phase IIa umbrella basket study.
Authors: Hainsworth John D. , Meric-Bernstam Funda , Swanton Charles , Hurwitz Herbert , Spigel David R. , Sweeney Christopher , Burris Howard A. , Bose Ron , Guo Shuangli , Bernaards Coen , Beattie Mary Stanley , Stein Alisha , Brammer Melissa , Kurzrock Razelle 
Published: May 2017

LBA11511 Background: The MyPathway study (NCT02091141) evaluates agents targeting the HER2, BRAF, Hedgehog (Hh), or EGFR pathways in non-indicated tumors with relevant genetic abnormalities. Early results from MyPathway merit pre-planned tumor-cohort expansion. Methods: Eligible pts had advanced solid tumors with no curative therapy and molecular alterations in HER2, BRAF, Hh, or EGFR. Pts received standard doses of trastuzumab + pertuzumab (for the HER2 pathway), vemurafenib (BRAF), vismodegib (Hh), or erlotinib (EGFR) based on alteration. The primary endpoint is investigator-evaluated response rate within a tumor-pathway cohort (RECIST 1.1). Cohort size and expansion is determined by Simon’s two-stage design criteria. Results: By December 14, 2015, MyPathway included 129 pts with available baseline assessments and alterations in HER2 (n = 82; 53 amplifications, 23 mutations, 5 both, 1 RBMS-NRG1 fusion), BRAF (n = 33; 18 V600E, 15 other), Hh (n = 8; 7 PTCH1, 1 SMO), or EGFR (n = 6). Pts had a median of 3 (range, 0–10) prior lines of therapy. Best responses (n = 118) are shown below; 11 pts had insufficient follow-up for reevaluation and were not analyzed. 22 pts had PR/CR (1 CR); current response durations were up to 11 months. Conclusions: Targeted therapy produced responses in pts with 9 different tumor types outside of current drug indications. As enrollment increases for all tumor-pathway cohorts, analyses of tumor responses based on specific alterations (eg, HER2 amplifications vs. mutations) are planned. The HER2 amplified colorectal, bladder, and biliary, and the BRAF lung cohorts will be expanded based on observed activity. Clinical trial information: NCT02091141. [Table: see text]
The Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research.
Authors: Wagle Nikhil , Painter Corrie , Krevalin Max , Oh Coyin , Anderka Kristin , Larkin Katie , Lennon Niall , Dillon Deborah , Frank Elizabeth , Winer Eric P. , Lander Eric , Golub Todd 
Published: May 2017

LBA1519 Background: The challenge in studying tumors from patients (pts) with metastatic breast cancer (MBC) has been that most tumors are not available for research, largely because most pts are cared for in community settings where genomics studies are not conducted. To address this, we launched a nationwide study, The Metastatic Breast Cancer Project, which seeks to empower patients to accelerate research by sharing their samples and clinical information. Methods: In collaboration with pts and advocacy groups, we developed a website to allow MBC pts to participate across the U.S. Enrolled pts are sent a saliva kit and asked to mail back a saliva sample, which is used to extract germline DNA. We contact participants’ medical providers and obtain medical records and part of their tumor biopsy. Whole exome and transcriptome sequencing is performed on tumor and germline. Clinically annotated genomic data are used to identify mechanisms of response and resistance to therapies. The database is shared widely with researchers. Study updates and discoveries are shared with participants regularly. Results: In the first 3 months, 1227 MBC pts enrolled. 1178 (96%) completed the 16-question survey about their cancer and treatments. Median age was 54 years (yrs) (range 25-91). Median time between initial diagnosis (dx) of breast cancer and MBC was 2 yrs; 424 pts were dx’d with de novo MBC. 1022 (87%) reported having a biopsy at or following their dx of MBC. Median time since MBC dx was 3 yrs; 87 reported having MBC >10 yrs. 436 (37%) reported being on a therapy for >2 yrs; 672 (57%) reported an “extraordinary response” to a therapy. For example, 77 reported long and/or extraordinary responses to capecitabine ; 44 to platinums, and 20 to everolimus. Initial medical records, saliva, and tumors have been received. Conclusions: A direct-to-patient approach enabled rapid identification of large numbers of MBC pts willing to share tumors, saliva, and medical records. This includes many with rare phenotypes, a group that has been challenging to identify with traditional approaches. Genomic analysis of pts with extraordinary responses and with de novo MBC are underway. Pt reported data has also identified unanticipated research questions.
OV21/PETROC: A randomized Gynecologic Cancer Intergroup (GCIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC).
Authors: Mackay Helen , Gallagher Christopher J. , Parulekar Wendy R. , Ledermann Jonathan A. , Armstrong Deborah Kay , Gourley Charlie , Romero Ignacio , Feeney Amanda , Bessette Paul , Hall Marcia , Weberpals Johanne Ingrid , Hall Geoff , Lau Susie K , Gauthier Philippe , Fung-Kee-Fung Michael , Eisenhauer Elizabeth A. , Winch Chad , Tu Dongsheng , Provencher Diane M. 
Published: May 2017

LBA5503 Background: The aim of this 2 stage randomized trial was to evaluate whether women undergoing neoadjuvant IV chemotherapy followed by delayed debulking surgery benefit from the addition of IP/IV treatment after surgery. Methods: Stage 1 was a randomized 3-arm design including 2 IP platinum regimens: 153 women who received 3-4 courses of IV platinum-based chemo for stage IIB-III (IV pleural effusion only) EOC followed by optimal debulking surgery ( < 1 cm) were randomized to: ARM1 D1 IV paclitaxel (pacli) 135mg/m2 + IV Carboplatin AUC 5/6 with d8 pacli IV 60 mg/m2 Q 21d X3; ARM 2 D1 IV pacli 135mg/m2 + IP cisplatin (Cis) 75 mg/m2 and d8 IP pacli 60 mg/m2 Q21d X3; or ARM 3 d1 IV pacli 135mg/m2+ IP Carboplatin AUC 5/6 and d8 IP pacli 60mg/m2 Q21dX3. A planned DSMC review confirmed dropping ARM2 (IP cis) and continuing study as an expanded phase II comparing 200 patients randomized to ARMs 1 and 3, which has 80% power to detect a 19% difference in progression rate at 9 mo (PD9, primary endpoint), 2-sided α = 0.05. Progression free survival (PFS) and overall survival (OS) are secondary efficacy endpoints. Results: Between 2009 and May 2015, 275 patients were accrued: n = 101 Arm 1, 72 Arm 2, 102 Arm 3. Median age was 62; 81.8%s had stage 3 C disease; 12.7% stage IV. Baseline characteristics were balanced between arms. Median number of cycles was 3 all arms; completion rates Arm 1, 93.7% and Arm 3, 84.8%. Intention to treat PD9 rates: Arm 1: 38.6% (95% CI 29.1%- 48.8%) and Arm 3: 24.5% (95% CI 16.5%-34.0%); p = 0.065 stratified; p = 0.03 unstratified. Per protocol (eligible, received > one dose of protocol therapy) PD9 rates: Arm 1: 42.2% (95% CI 31.9%- 53.1%), Arm 3: 23.3% (95% CI 15.1%-33.4%); p = 0.03 stratified; p = 0.01 unstratified. Median PFS 11.3 mo (Arm1) and 12.5 mo (Arm 3); HR 0.82 (95% CI 0.57 - 1.17); p = 0.27. Median OS: 38.1 mo (Arm 1) and 59.3 mo (Arm 3); HR 0.80 (95% CI 0.47-1.35) p = 0.40. Adverse events > Gr 3 rates: 23% (Arm 1) and 16% (Arm 3) (p = 0.24). Conclusions: The IP carboplatin based regimen, post neoadjuvant chemotherapy and debulking surgery, is well tolerated and associated with a lower PD9 rate compared to IV therapy. Clinical trial information: NCT00993655.
Global differences in cancer drug prices: A comparative analysis.
Authors: Goldstein Daniel A. , Clark Jonathon , Tu Yifan , Zhang Jie , Fang Fenqi , Goldstein Robert Michael , Stemmer Salomon M. , Rosenbaum Eli 
Published: May 2017

LBA6500 Background: Cancer drug prices are different in every country in the world, however, little is known about the magnitude of these differences. The primary objective of this study was to describe the differences in prices globally. The secondary objective was to understand ability to pay, using gross domestic product per capita at purchasing power parity (GDPcap), as a surrogate. Methods: We calculated monthly drug doses for 23 cancer drugs, 15 of which are available generically. We then calculated monthly drug prices from 6 countries on 5 different continents: Australia (AUS), China (CHI), India (IND), South Africa (SA), United Kingdom (UK), and United States (US). Given the lack of availability of discounted prices, we used list prices in order to make appropriate comparisons. Prices were obtained from locally and nationally recognized institutions. The monthly cost was converted to US$ at the exchange rate ruling on 19 January 2016. We obtained GDPcap data for each country from the International Monetary Fund, in order to estimate the monthly drug price as a percentage of GDPcap. Results: Results are displayed in the table. The median monthly patented drug price ranged from US$1515 (IND) to $8694 (US). The median monthly generic drug price ranged from US$120 (SA) to $654 (US). The median monthly % of GDPcap for patented drugs ranged from 71% (AUS) to 313% (IND). The median monthly % of GDPcap for generic drugs ranged from 3% (AUS) to 48% (CHI). Detailed information regarding specific drugs will be presented. Conclusions: There is a wide variation in drug prices globally. Despite lower prices in poorer countries, both generic and patented drugs appear to be less affordable in poorer countries. Price differences likely have some impact on access to care within individual countries. [Table: see text]
Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC).
Authors: Rudin Charles M. , Pietanza Maria Catherine , Bauer Todd Michael , Spigel David R. , Ready Neal , Morgensztern Daniel , Glisson Bonnie S. , Byers Lauren Averett , Johnson Melissa Lynne , Burris Howard A. , Robert Francisco , Strickland Donald K , Zayed Hany , Govindan Ramaswamy , Dylla Scott , Peng Stanford L. 
Published: May 2017

LBA8505 Background: SCLC remains among the most deadly of malignancies. Rovalpituzumab tesirine is a first-in-class ADC comprised of a humanized monoclonal antibody against DLL3, a dipeptide linker, and a pyrrolobenzodiazepine (PBD) dimer toxin. DLL3 is highly expressed in neuroendocrine tumors, including approximately 80% of SCLC. The emerging results of the SCLC patients (pts) in a first-in-human study (NCT01901653) are reported here. Methods: Pts with progressive SCLC after at least 1 previous systemic therapy were eligible. Efficacy was assessed by the investigator via RECIST v1.1, and toxicity graded per CTCAE v4.03. When available, archived tumor tissue was assessed retrospectively for DLL3 expression by immunohistochemistry. Results: Seventy-four (74) pts were enrolled at dose levels ranging from 0.05 to 0.8 mg/kg at either q3w or q6w. Among evaluable pts treated at doses of 0.2-0.4 mg/kg, 15/61 (25%; 95% CI 15-37%) achieved a best response of PR or CR, and 44/61 (72%; 95% CI 59-83%) achieved clinical benefit (best response of at least SD). Among pts with available archive tissue specimens and ≥ 50% of cells expressing DLL3 (DLL3hi, an intended companion diagnostic cutoff), 12/22 (55%; 95% CI 32-76%) achieved a best response of PR or CR, and 20/22 (91%; 95% CI 71-99%) achieved clinical benefit, with a median overall survival of 8 (range 1-18+) months. In 3rd line DLL3hi pts (n = 10), where no approved therapy currently exists, the ORR and CBR were 70% and 90%, respectively, with at least 4 evaluable pts achieving OS of > 6 (8, 15, 18 and 18) months. Among responders treated at the phase 2 dose of 0.3 mg/kg, the median duration of response was 6 (range 1-8+) months. Among all SCLC pts, the most common grade 3+ toxicities considered study drug-related have included serosal effusions (14%), thrombocytopenia (12%) and skin reactions (8%). Conclusions: With manageable toxicity, rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity and durability in recurrent or refractory SCLC. A single-arm pivotal study in 3rd line DLL3-expressing SCLC has been initiated. Clinical trial information: NCT01901653.