bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Bone Bruise Characteristics and Articular Cartilage Pathology Associated with Inferior Outcomes 2 and 6 Years After Anterior Cruciate Ligament Reconstruction?
Authors: Lattermann Christian , Jacobs Cale A. , Reinke Emily K. , Scaramuzza Erica A. , Huston Laura J. , Dunn Warren R. , Spindler Kurt P.
Published: June 2016

Objective

To determine (1) if bone bruise characteristics seen on magnetic resonance imaging are associated with patient-reported outcomes prior to and following anterior cruciate ligament reconstruction and (2) if the combined presence of bone bruises with articular cartilage pathology results in inferior 2- or 6-year outcomes.

Design

Bone bruise volume and severity were measured on 81 patients’ preoperative magnetic resonance imaging in the medial and lateral femoral condyle (MFC, LFC) and medial and lateral tibial plateau (MTP, LTP) using the Costa-Paz classification and a modified version of Roemer and Bohndorf’s technique. The relationships between bone bruise volume and severity with Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) scores were assessed, and pre- and postoperative KOOS and IKDC scores were compared between those with bone bruises either with or without combined local articular cartilage pathology.

Results

All 81 patients had a bone bruise in at least 1 region and 70 (86%) had bone bruises in ≥2 regions. LTP bruises were the most common (76/81, 94%), followed by the LFC (66, 81%), MTP (46, 57%), and MFC (20, 25%). Neither bone bruise volume nor severity was associated with inferior postoperative outcomes. The subset of 17 patients with bone bruises and combined articular cartilage pathology were 3.4 times more likely to be symptomatic at 6-year follow-up than those without articular cartilage pathology ( P = 0.04).

Conclusions

The volume and severity of preoperative bone bruises alone were not associated with 2- or 6-year outcomes; however, bone bruises combined with local articular cartilage pathology appear to be more symptomatic after ACL reconstruction.
Improving the robustness of reinforced concrete framed structures under sudden column losses
Authors: Elkholy Said , El-Ariss Bilal
Published: June 2016

Recent guidelines have addressed provisions to improve structure integrity to accommodate progressive collapse due to failure of an interior support. This article presents novel technique and numerical model to enhance and evaluate reinforced concrete frame robustness to progressive collapse triggered by an interior or edge column failure in any floor. The presented technique enhances the structure robustness to progressive collapse by providing sufficient ductility, continuity, and redundancy. The technique involves placing external unbounded steel cables attached to the continuous beam in each floor at anchorage and deviator locations to bridge over a damaged column of any floor of the frame. The cables transfer the loads above the failed column to the anchorages and deviators that are assumed to perform as rigid arms, which in turn redistribute the loads to adjacent columns. The numerical model computes the frame building progressive collapse robustness using push-down analysis to simulate a column elimination and estimate the effects of cable catenary action on the frame. Two-dimensional reinforced concrete frame of six stories and four bays was adopted in the study. The numerical results demonstrate the prospect of resisting progressive collapse of reinforced concrete structures by implementing the presented technique.
Field testing and numerical investigation of streetscape vehicular anti-ram barriers under vehicular impact using FEM-only and coupled FEM-SPH simulations
Authors: Yoo Tae Kwang , Qiu Tong , Reese Lynsey , Rado Zoltan
Published: June 2016

This article presents two field-scale crash tests of Streetscape Vehicle Anti-Ram barrier systems and LS-DYNA simulations to predict the global response of each system under vehicular impact. Tests 1 and 2 consisted of a five-post welded bus stop and a welded bollard, respectively; both were in a steel and concrete composite foundation embedded in compacted American Association of State Highway and Transportation Officials aggregate. Test 1 resulted in a P1 rating, where minimal foundation uplift and rotation were observed. Test 2 failed to result in a P1 rating, where significant foundation uplift, rotation, concrete cracking, and large deformation of surrounding soil were observed. For each test, two LS-DYNA models, namely, a finite element method–only model and a hybrid finite element method–smoothed particle hydrodynamics model, were created to predict the global response of the system. In the finite element method–only model, traditional finite element method approach was used for the entire soil region; in the hybrid finite element method–smoothed particle hydrodynamics model, the near-field soil region was modeled using the smoothed particle hydrodynamics approach, whereas the far-field soil region was modeled using the finite element method approach. For Test 1, both the finite element method–only model and the hybrid finite element method–smoothed particle hydrodynamics model were able to match the recorded global response of the system. For Test 2, however, the finite element method–only approach was not able to accurately predict the global response of the system; on the other hand, the hybrid finite element method–smoothed particle hydrodynamics approach was able to capture the global response including the bollard pullout, soil upheaval, and vehicle override. This research suggests that the hybrid finite element method–smoothed particle hydrodynamics approach is more appropriate in simulating the field performance of embedded structures under impact loading when large deformation of the surrounding soil is expected.
Surveillance of Bosniak IIF renal cysts: Rationalising follow-up policy
Authors: Raslan Mutie , Tolofari Sotonye K , Bromby Adam , Costa Diogo , Maddineni Satish B , Cowie Alistair , O’Dwyer Catherine , O’Flynn Kieran J
Published: June 2016

Objectives:

To assess the clinical outcomes of patients diagnosed with Bosniak IIF renal cysts, in order to rationalise our surveillance policy.

Patients and methods:

We identified all patients diagnosed with a Bosniak IIF cyst between September 2011 and September 2014. Patient demographics, duration, frequency and modality of surveillance were recorded. Changes in the size, appearance or characteristics of the cyst(s) were recorded, as well as any subsequent surgery and histology. We also estimated the overall cost of imaging and follow up.

Results:

We identified 198 patients. The majority of IIF cysts were incidental findings (86.5%), with 56% of cysts > 3 cm at diagnosis. Median follow-up time was 27 months. We found that 98% of cysts were unchanged in their Bosniak score and 66% did not change in size. We followed up on 86 patients (43%) beyond two years: None had radiological progression. Four patients (2%) underwent partial nephrectomy secondary to radiological progression: One (0.5%) had histological malignancy. Features of malignancy were noticed in the first 24 months of the follow-up period.

Conclusions:

Radiological progression of Bosniak IIF cysts is low and progression to malignancy lower still, typically occurring within 24 months of diagnosis. Our data suggested that ceasing radiological follow-up surveillance after a minimum of two years of stable surveillance could be considered. Rational follow-up protocols for Bosniak IIF cysts would have significant cost-saving implications for the National Health Service (NHS) and alleviate pressure on radiology and urology services.
Anterior prostate cancer: Current perspectives and diagnostic dilemmas
Authors: Sahu Mahua , Wijesekera Nevin , Donohue John F
Published: June 2016

Anterior zone (transition zone and anterior horn of peripheral zone) tumours represent 20–30% of all prostate cancers. Traditional transrectal prostate biopsies fail to sample this area of the prostate gland adequately, thereby underestimating the true extent of anterior zone cancers. This article outlines the behaviour and significance of this entity and discusses investigations that are currently available which may aid in their detection. The implementation of transperineal template-guided prostate biopsies will allow optimal sampling of the anterior zone whilst advances in the field of magnetic resonance imaging allow the use of multiple sequences (T2-weighted, spectroscopy, diffusion weighted and dynamic contrast enhancement) to identify these tumours accurately. Such investigations will result in more accurate risk stratification compared with the current diagnostic pathway, and could lead to improved management in this subset of men.
Big Data in food and agriculture
Authors: Bronson Kelly , Knezevic Irena
Published: June 2016

Farming is undergoing a digital revolution. Our existing review of current Big Data applications in the agri-food sector has revealed several collection and analytics tools that may have implications for relationships of power between players in the food system (e.g. between farmers and large corporations). For example, Who retains ownership of the data generated by applications like Monsanto Corproation's Weed I.D. “app”? Are there privacy implications with the data gathered by John Deere's precision agricultural equipment? Systematically tracing the digital revolution in agriculture, and charting the affordances as well as the limitations of Big Data applied to food and agriculture, should be a broad research goal for Big Data scholarship. Such a goal brings data scholarship into conversation with food studies and it allows for a focus on the material consequences of big data in society.
Critical Data Studies: A dialog on data and space
Authors: Dalton Craig M , Taylor Linnet , Thatcher (alphabetical) Jim
Published: June 2016

In light of recent technological innovations and discourses around data and algorithmic analytics, scholars of many stripes are attempting to develop critical agendas and responses to these developments (boyd and Crawford 2012). In this mutual interview, three scholars discuss the stakes, ideas, responsibilities, and possibilities of critical data studies. The resulting dialog seeks to explore what kinds of critical approaches to these topics, in theory and practice, could open and make available such approaches to a broader audience.
From Marikana to #feesmustfall: The Praxis of Popular Politics in South Africa
Authors: Naicker Camalita
Published: June 2016

This article explores the forms of popular politics that rose out of massive student protests in South Africa at the end of 2015. By delving deeper into the way higher education has been structured in post-apartheid South Africa, the author explains the ways in which race and class privilege have been reified in South African universities. The spatial location of the university within South Africa and the place of the university within the African continent is not reflected in institutional culture of higher education but is deeply embedded in the student protests. By exploring the collective decision making structures of students the author explores students growing lack of faith in higher education institutions to effect any transformational change.
Why Another Journal? Setting up Environment and Urbanization in 1989
Authors: Satterthwaite David
Published: June 2016

This article describes why we set up the journal Environment and Urbanization with a focus on the global south, and on authors from the south. It now has over 10,000 subscribers, helped by schemes that allow free subscriptions to institutions in the south. The journal has always sought to engage with and publish practitioners as well as academics, and wherever possible, grassroots leaders and politicians. It has had a strong history of documenting local innovation on the part of local governments, NGOs and grassroots organisations and federations, and providing exposure for initiatives that might not otherwise be documented.
Implementing the Global Goals in City Regions
Authors: Head Peter
Published: June 2016

This article describes the vision as well as the details behind a new open source digital planning platform named, resilience.io that is designed to support disaster risk reduction and management, delivery of the Global Goals, deep decarbonisation, and connecting financing opportunities to projects that are inclusive, resilient, and sustainable. Drawing from the experience of a lifetime on urban practice in infrastructure and planning, this informational gateway is designed to document the material, topographic and process world of urban transformation as well as to influence institutional decisions to adopt resilient processes and outcomes. This intends to contribute to the global initiative to bring economic success to a world in which human well-being is improved while using resources in a resilient way and where resource use is circular and regenerative. At the heart of the resilience.io systems model are the links between ecology, resources and human well-being.
Land-based Financing in Metropolitan Cities in India: The Case of Hyderabad and Mumbai
Authors: Gandhi Sahil , Phatak Vidyadhar K.
Published: June 2016

Major cities in developing countries face infrastructure shortage and inadequate financial outlays to overcome it. One way to raise finances is by leveraging the increasing urban land values using different mechanisms. This article studies the experience of land-based financing in the metropolitan cities of Hyderabad and Mumbai in India. It assesses the performance of various mechanisms implemented by the principal urban local bodies and development authorities in these cities by examining their design, collections and utilisation of revenues from land-based financing mechanisms for infrastructure provision. It finds that although land-based financing contributes substantially to revenues of public bodies, there are issues regarding efficacy of design and legal validity that need to be addressed to make it sustainable. Further, the article finds that to a certain extent, some of the public organisations use revenues from land-based financing for capital expenditure.
Synthetic tetracycline-controllable shRNA targeting long non-coding RNA HOXD-AS1 inhibits the progression of bladder cancer
Authors: Li Jianfa , Zhuang Chengle , Liu Yuchen , Chen Mingwei , Chen Yincong , Chen Zhicong , He Anbang , Lin Junhao , Zhan Yonghao , Liu Li , Xu Wen , Zhao Guoping , Guo Yinglu , Wu Hanwei , Cai Zhiming , Huang Weiren
Published: June 2016

Background

Long non-coding RNAs (lncRNAs) have been proved to act as key molecules in cancer development and progression. Dysregulation of lncRNAs is discovered in various tumor tissues and cancer cells where they can serve as oncogenes or tumor suppressors. Long non-coding RNA HOXD-AS (HOXD cluster antisense RNA 1) has recently been identified to be involved in the development of several cancers including neuroblastoma, adenocarcinomas and breast cancer. However, the role of HOXD-AS1 in bladder cancer remains unknown.

Methods

The synthetic tetracycline-controllable shRNA was used to modulate the level of HOXD-AS1 by adding different concentrations of doxycycline (dox). RT-qPCR was used to detect the expression level of HOXD-AS1. Cell proliferation was determined by CCK-8 assay and EdU incorporation experiment when HOXD-AS1 was knocked down. We used wound-healing assay for detecting the effect of HOXD-AS1 on cell migration. Eventually, cell apoptosis was determined by caspase 3 ELISA assay and flow cytometry assay.

Results

In this study, we found that the expression level of HOXD-AS1 was significantly increased in bladder cancer tissues and cells. Furthermore, high expression of HOXD-AS1 was significantly related to tumor size, histological grade and TNM stage. In vitro assays confirmed that knockdown of HOXD-AS1 suppressed cell proliferation/migration and increased the rate of apoptotic cell in bladder cancer cells. At last, we used the important element of synthetic biology, tetracycline(tet)-controllable switch, to construct tet-controllable shRNA vectors which can modulate the expression of HOXD-AS1 in a dosage-dependent manner.

Conclusions

Our research suggested that high expression of HOXD-AS1 may be involved in the bladder cancer carcinogenesis through inhibiting the phenotypes and activating endogenous cancer-related molecular pathways. Therefore, HOXD-AS1 may act as an oncogene and provide a potential attractive therapeutic target for bladder cancer. In addition, the synthetic tetracycline-controllable shRNA may provide a novel method for cancer research in vitro assays.
RETRACTED ARTICLE: TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells
Authors: Wang Xiaolin , Shi Weiping , Shi Hongcan , Lu Shichun , Wang Kang , Sun Chao , He Jiansheng , Jin Weiguo , Lv Xiaoxia , Zou Hui , Shu Yusheng
Published: June 2016

Background

Tripartite Motif Containing 11 (TRIM11), a member of TRIM proteins, is overexpressed in high-grade gliomas and plays an oncogenic function in glioma biology. However, little is known about the role of TRIM11 in lung cancer.

Methods

We analyzed TRIM11 mRNA expression in lung cancer tissues and adjacent non-neoplastic tissues by real-time PCR. We then explored the function of TRIM11 in lung cancer cells by small interfering RNA-mediated downregulation of this protein followed by analyses of cell proliferation, migration and invasion.

Results

TRIM11 was highly expressed in lung cancer tissues and lung cancer cell lines. The higher expression of TRIM11 was correlated with the poorer prognosis of patients. Suppressing of TRIM11 expression in lung cancer cells with higher expression of TRIM11 (A549 and NCI-H446 cells) significantly reduced cell growth, motility and invasiveness. We further demonstrated that knockdown of TRIM11 affected the expression of cell proliferation-related proteins (Cyclin D1 and PCNA), and epithelial-mesenchymal transformation-related proteins (VEGF, MMP-2, MMP-9, Twist1, Snail and E-cadherin). The activity of ERK and PI3K/AKT was also suppressed in TRIM11 knocked down cells. Further experiments in lung cells with lower expression of TRIM11 (NCI-H460 and NCI-H1975 cells) with AKT inhibitor suggested that TRIM11 may promote cell motility and invasiveness through AKT pathway.

Conclusions

Our results indicate that TRIM11 acts as an oncogene in lung cancer through promoting cell growth, migration and invasion. Our findings may have important implication for the detection and treatment of lung cancer.
Evaluation of the otolith function using c/oVEMPs in patients with Ménière's disease
Authors: Chen Liang , Xu Hui , Wang Wu-qing , Zhang Qing-quan , Lv Qiao-ying , Song Xi-cheng
Published: June 2016

Background

Cervical and ocular vestibular evoked myogenic potentials (c/oVEMPs) reflect otolith function. Up-to-date, there are no published reports on the systemic evaluation of otolith function in Ménière's Disease (MD) nor are there any reports on the differences in VEMPs between patients with early and late stage MD. The aim of this study was to evaluate the difference in c/oVEMPs between patients with MD and normal controls, as well as between patients with early and late stage MD.

Methods

Thirty patients with unilateral MD and thirty healthy subjects (as normal controls) were prospectively enrolled. c/oVEMPs using 500 Hz tone-burst stimuli were performed. VEMP tests were repeated 3 times on each subject to ensure reliability and reproducibility of responses. VEMPs were defined as present or absent. Abnormal VEMP was defined by lack of VEMP response.

Results

In the control group, abnormal cVEMPs and oVEMPs responses were detected in 6.67 and 3.34 % respectively. In MD patients (20 with early stage MD [ES-MD], 10 with late stage MD [LS-MD]), abnormal cVEMPs and oVEMPs responses were detected in 40 and 16.7 % respectively. More patients with MD showed abnormal responses in c/oVEMPs as compared to the control group ( p < 0.05). cVEMPs was more often abnormal as compared to oVEMPs in MD patients ( p < 0.05). There was a significant difference in abnormal cVEMP responses between ES-MD patients (25 %) and LS-MD patients (70 %) ( p < 0.05). Difference in abnormal oVEMP responses (ES-MD, 5 %; LS-MD, 40 %) was significant ( p < 0.05).

Conclusion

An increased occurrence of abnormal c/oVEMP recordings appeared in MD patients, possibly as a result of hydrops of the otolith. cVEMPs were more often abnormal in MD patients as compared to oVEMPs, suggesting that saccular dysfunction may be more common than utricular dysfunction. Furthermore, o/cVEMP abnormalities in the LS-MD group were significantly higher than those in the ES-MD group, suggesting the trend that otolith damage is gradually increasing with the aggravation of cochlear injury in MD.
Multiple genetically engineered humanized microenvironments in a single mouse
Authors: Lee Jungwoo , Heckl Dirk , Parekkadan Biju
Published: June 2016

Background

Immunodeficient mouse models that accept human cell and tissue grafts can contribute greater knowledge to human stem cell research. In this technical report, we used biomaterial implants seeded with genetically engineered stromal cells to create several unique microenvironments in a single mouse. The scope of study was focused on human CD34 hematopoietic stem/progenitor cell (HSPC) engraftment and differentiation within the engineered microenvironment.

Results

A mouse model system was created using subdermal implant sites that overexpressed a specific human cytokines (Vascular Endothelial Growth Factor A (hVEGFa), Stromal Derived Factor 1 Alpha (hSDF1a), or Tumor Necrosis Factor Alpha (hTNFa)) by stromal cells in a three-dimensional biomaterial matrix. The systemic exposure of locally overexpressed cytokines was minimized by controlling the growth of stromal cells, which led to autonomous local, concentrated sites in a single mouse for study. This biomaterial implant approach allowed for the local analysis of each cytokine on hematopoietic stem cell recruitment, engraftment and differentiation in four different tissue microenvironments in the same host. The engineered factors were validated to have bioactive effects on human CD34+ hematopoietic progenitor cell differentiation.

Conclusions

This model system can serve as a new platform for the study of multiple human proteins and their local effects on hematopoietic cell biology for in vivo validation studies.
Morphometric evaluation of wound healing in burns treated with Ulmo (Eucryphia cordifolia) honey alone and supplemented with ascorbic acid in guinea pig (Cavia porcellus)
Authors: Schencke Carolina , Vasconcellos Adriana , Sandoval Cristian , Torres Paulina , Acevedo Francisca , del Sol Mariano
Published: June 2016

Background

In the context of the search for cost-efficient treatments, Ulmo (Eurcyphia cordifolia) honey is an excellent alternative for treating burn wounds and could have a profound medical, social, and economic impact. Ascorbic acid is an enzymatic co-factor necessary for the synthesis of collagen and the proliferation of fibroblasts and has been proposed as a coadjuvant to strengthen the healing effects of honey. The aim of this work was to evaluate by morphometric studies the healing wounds caused by burns treated with Ulmo honey alone and supplemented with ascorbic acid in guinea pig (Cavia porcellus).

Methods

Fifteen guinea pigs were used and divided randomly into three groups: positive control (C+), experimental with unsupplemented honey (H), and experimental with supplemented honey (SH). A uniform deep burn covering 1 cm2 of the back skin was performed. The following indices were calculated for the morphometric study: superficial contraction index of the wound, deep contraction index of the wound, wound severity index, global healing index, global contraction index, and dermal proliferation area.

Results

The superficial contraction index of the wound, global healing index, global contraction, and dermal proliferation area values of the experimental with supplemented honey group were higher than the other groups (P < 0.05).

Conclusions

According to these results, the combination of honey with an antioxidant (ascorbic acid) promotes an appropriate action to support the healing effect. This study showed that by supplementing the Ulmo honey with ascorbic acid, the healing and contraction effects can be strengthened in burn wounds compared to unsupplemented honey. These results were proof of the synergy between honey and ascorbic acid in healing burn wounds.
Efficacy of Mindfulness-Based Cognitive Therapy on Late Post-Treatment Pain in Women Treated for Primary Breast Cancer: A Randomized Controlled Trial
Authors: Johannsen Maja , O’Connor Maja , O’Toole Mia Skytte , Jensen Anders Bonde , Højris Inger , Zachariae Robert
Published: June 2016

Purpose

To assess the efficacy of mindfulness-based cognitive therapy (MBCT) for late post-treatment pain in women treated for primary breast cancer.

Methods

A randomized wait list–controlled trial was conducted with 129 women treated for breast cancer reporting post-treatment pain (score ≥ 3 on pain intensity or pain burden assessed with 10-point numeric rating scales). Participants were randomly assigned to a manualized 8-week MBCT program or a wait-list control group. Pain was the primary outcome and was assessed with the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2), the Present Pain Intensity subscale (the McGill Pain Questionnaire), and perceived pain intensity and pain burden (numeric rating scales). Secondary outcomes were quality of life (World Health Organization-5 Well-Being Index), psychological distress (the Hospital Depression and Anxiety Scale), and self-reported use of pain medication. All outcome measures were assessed at baseline, postintervention, and 3-month and 6-month follow-up. Treatment effects were evaluated with mixed linear models.

Results

Statistically significant time × group interactions were found for pain intensity (d = 0.61; P = .002), the Present Pain Intensity subscale (d = 0.26; P = .026), the SF-MPQ-2 neuropathic pain subscale (d = 0.24; P = .036), and SF-MPQ-2 total scores (d = 0.23; P = .036). Only pain intensity remained statistically significant after correction for multiple comparisons. Statistically significant effects were also observed for quality of life (d = 0.42; P = .028) and nonprescription pain medication use (d = 0.40; P = .038). None of the remaining outcomes reached statistical significance.

Conclusion

MBCT showed a statistically significant, robust, and durable effect on pain intensity, indicating that MBCT may be an efficacious pain rehabilitation strategy for women treated for breast cancer. In addition, the effect on neuropathic pain, a pain type reported by women treated for breast cancer, further suggests the potential of MBCT but should be considered preliminary.
Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial
Authors: Pavlakis Nick , Sjoquist Katrin M. , Martin Andrew J. , Tsobanis Eric , Yip Sonia , Kang Yoon-Koo , Bang Yung-Jue , Alcindor Thierry , O’Callaghan Christopher J. , Burnell Margot J. , Tebbutt Niall C. , Rha Sun Young , Lee Jeeyun , Cho Jae-Yong , Lipton Lara R. , Wong Mark , Strickland Andrew , Kim Jin Won , Zalcberg John R. , Simes John , Goldstein David
Published: June 2016

Purpose

We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma.

Patients and Methods

We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014.

Results

A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P < .001). The effect was greater in South Korea than in Australia, New Zealand, and Canada combined (HR, 0.12 v 0.61; interaction P < .001) but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, peritoneal metastasis presence, number of metastatic sites, and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported.

Conclusion

In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.
Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor–Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
Authors: Colleoni Marco , Gray Kathryn P. , Gelber Shari , Láng István , Thürlimann Beat , Gianni Lorenzo , Abdi Ehtesham A. , Gomez Henry L. , Linderholm Barbro K. , Puglisi Fabio , Tondini Carlo , Kralidis Elena , Eniu Alexandru , Cagossi Katia , Rauch Daniel , Chirgwin Jacquie , Gelber Richard D. , Regan Meredith M. , Coates Alan S. , Price Karen N. , Viale Giuseppe , Goldhirsch Aron
Published: June 2016

Purpose

To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer.

Patients and Methods

International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor– and progesterone receptor–negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths.

Results

After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%).

Conclusion

CM maintenance did not produce a significant reduction in DFS events in hormone receptor–negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
Randomized Noninferiority Trial of Telephone Delivery of BRCA1/2 Genetic Counseling Compared With In-Person Counseling: 1-Year Follow-Up
Authors: Kinney Anita Y. , Steffen Laurie E. , Brumbach Barbara H. , Kohlmann Wendy , Du Ruofei , Lee Ji-Hyun , Gammon Amanda , Butler Karin , Buys Saundra S. , Stroup Antoinette M. , Campo Rebecca A. , Flores Kristina G. , Mandelblatt Jeanne S. , Schwartz Marc D.
Published: June 2016

Purpose

The ongoing integration of cancer genomic testing into routine clinical care has led to increased demand for cancer genetic services. To meet this demand, there is an urgent need to enhance the accessibility and reach of such services, while ensuring comparable care delivery outcomes. This randomized trial compared 1-year outcomes for telephone genetic counseling with in-person counseling among women at risk of hereditary breast and/or ovarian cancer living in geographically diverse areas.

Patients and Methods

Using population-based sampling, women at increased risk of hereditary breast and/or ovarian cancer were randomly assigned to in-person (n = 495) or telephone genetic counseling (n = 493). One-sided 97.5% CIs were used to estimate the noninferiority effects of telephone counseling on 1-year psychosocial, decision-making, and quality-of-life outcomes. Differences in test-uptake proportions for determining equivalency of a 10% prespecified margin were evaluated by 95% CIs.

Results

At the 1-year follow-up, telephone counseling was noninferior to in-person counseling for all psychosocial and informed decision-making outcomes: anxiety (difference [d], 0.08; upper bound 97.5% CI, 0.45), cancer-specific distress (d, 0.66; upper bound 97.5% CI, 2.28), perceived personal control (d, −0.01; lower bound 97.5% CI, −0.06), and decisional conflict (d, −0.12; upper bound 97.5% CI, 2.03). Test uptake was lower for telephone counseling (27.9%) than in-person counseling (37.3%), with the difference of 9.4% (95% CI, 2.2% to 16.8%). Uptake was appreciably higher for rural compared with urban dwellers in both counseling arms.

Conclusion

Although telephone counseling led to lower testing uptake, our findings suggest that telephone counseling can be effectively used to increase reach and access without long-term adverse psychosocial consequences. Further work is needed to determine long-term adherence to risk management guidelines and effective strategies to boost utilization of primary and secondary preventive strategies.
Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials
Authors: Hershman Dawn L. , Till Cathee , Wright Jason D. , Awad Danielle , Ramsey Scott D. , Barlow William E. , Minasian Lori M. , Unger Joseph
Published: June 2016

Background

Neuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy.

Methods

We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy.

Results

A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P < .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy.

Conclusion

We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic complications may choose to avoid paclitaxel or taxane plus platinum combination therapies if other efficacious options exist.
Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population
Authors: Bower Hannah , Björkholm Magnus , Dickman Paul W. , Höglund Martin , Lambert Paul C. , Andersson Therese M.-L.
Published: June 2016

Purpose

A dramatic improvement in the survival of patients with chronic myeloid leukemia (CML) occurred after the introduction of imatinib mesylate, the first tyrosine kinase inhibitor (TKI). We assessed how these changes affected the life expectancy of patients with CML and life-years lost as a result of CML between 1973 and 2013 in Sweden.

Materials and Methods

Patients recorded as having CML in the Swedish Cancer Registry from 1973 to 2013 were included in the study and followed until death, censorship, or end of follow-up. The life expectancy and loss in expectation of life were predicted from a flexible parametric relative survival model.

Results

A total of 2,662 patients with CML were diagnosed between 1973 and 2013. Vast improvements in the life expectancy of these patients were seen over the study period; larger improvements were seen in the youngest ages. The great improvements in life expectancy translated into great reductions in the loss in expectation of life. Patients of all ages diagnosed in 2013 will, on average, lose < 3 life-years as a result of CML.

Conclusion

Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today. This will be an important message to convey to patients to understand the impact of a CML diagnosis on their life. In addition, the increasing prevalence of patients with CML will have a great effect on future health care costs as long as continuous TKI treatment is required.
Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival
Authors: Yuan Chen , Qian Zhi Rong , Babic Ana , Morales-Oyarvide Vicente , Rubinson Douglas A. , Kraft Peter , Ng Kimmie , Bao Ying , Giovannucci Edward L. , Ogino Shuji , Stampfer Meir J. , Gaziano John Michael , Sesso Howard D. , Buring Julie E. , Cochrane Barbara B. , Chlebowski Rowan T. , Snetselaar Linda G. , Manson JoAnn E. , Fuchs Charles S. , Wolpin Brian M.
Published: June 2016

Purpose

Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored.

Patients and Methods

We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ≥ 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance.

Results

Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01).

Conclusion

We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.
The Effects of Oncologist Implicit Racial Bias in Racially Discordant Oncology Interactions
Authors: Penner Louis A. , Dovidio John F. , Gonzalez Richard , Albrecht Terrance L. , Chapman Robert , Foster Tanina , Harper Felicity W.K. , Hagiwara Nao , Hamel Lauren M. , Shields Anthony F. , Gadgeel Shirish , Simon Michael S. , Griggs Jennifer J. , Eggly Susan
Published: June 2016

Purpose

Health providers’ implicit racial bias negatively affects communication and patient reactions to many medical interactions. However, its effects on racially discordant oncology interactions are largely unknown. Thus, we examined whether oncologist implicit racial bias has similar effects in oncology interactions. We further investigated whether oncologist implicit bias negatively affects patients’ perceptions of recommended treatments (i.e., degree of confidence, expected difficulty). We predicted oncologist implicit bias would negatively affect communication, patient reactions to interactions, and, indirectly, patient perceptions of recommended treatments.

Methods

Participants were 18 non-black medical oncologists and 112 black patients. Oncologists completed an implicit racial bias measure several weeks before video-recorded treatment discussions with new patients. Observers rated oncologist communication and recorded interaction length of time and amount of time oncologists and patients spoke. Following interactions, patients answered questions about oncologists’ patient-centeredness and difficulty remembering contents of the interaction, distress, trust, and treatment perceptions.

Results

As predicted, oncologists higher in implicit racial bias had shorter interactions, and patients and observers rated these oncologists’ communication as less patient-centered and supportive. Higher implicit bias also was associated with more patient difficulty remembering contents of the interaction. In addition, oncologist implicit bias indirectly predicted less patient confidence in recommended treatments, and greater perceived difficulty completing them, through its impact on oncologists’ communication (as rated by both patients and observers).

Conclusion

Oncologist implicit racial bias is negatively associated with oncologist communication, patients’ reactions to racially discordant oncology interactions, and patient perceptions of recommended treatments. These perceptions could subsequently directly affect patient-treatment decisions. Thus, implicit racial bias is a likely source of racial treatment disparities and must be addressed in oncology training and practice.
Survival Analyses of Patients With Metastatic Renal Cancer Treated With Targeted Therapy With or Without Cytoreductive Nephrectomy: A National Cancer Data Base Study
Authors: Hanna Nawar , Sun Maxine , Meyer Christian P. , Nguyen Paul L. , Pal Sumanta K. , Chang Steven L. , de Velasco Guillermo , Trinh Quoc-Dien , Choueiri Toni K.
Published: June 2016

Purpose

The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has become unclear since the introduction of targeted therapies (TT). We sought to evaluate contemporary utilization rates of CN and to examine the survival benefit of CN compared with non-CN patients treated with TT.

Methods

We used the National Cancer Data Base to identify patients with clinical mRCC treated with TT between 2006 and 2013. The intervention of interest was CN. Multivariable logistic regression predicting receipt of CN was performed. Overall survival (OS) was examined using Cox regression models and incremental survival analyses were performed. Sensitivity analyses using propensity scores were conducted.

Results

Of 15,390 patients treated with TT, 5,374 (35%) underwent CN between 2006 and 2013. Patients who were younger, privately insured, treated at an academic center, and had lower tumor stage and cN0 disease were more likely to undergo CN. The median OS of CN versus non-CN patients was 17.1 (95% CI, 16.3 to 18.0 months) versus 7.7 months (95% CI, 7.4 to 7.9 months; P < .001). In sensitivity analyses using propensity scores adjustment in addition to other available covariates, CN patients had a lower risk of any death (hazard ratio, 0.45; 95% CI, 0.40 to 0.50; P < .001). The survival benefit of CN was +0.7 and +3.6 months in patients who survived ≤ 6 and ≤ 24 months, respectively, versus no CN.

Conclusion

CN is performed in three of 10 patients with mRCC who are receiving TT. Several patient and sociodemographic characteristics were associated with receipt of CN. When feasible, CN may offer an OS benefit when combined with TT.