tbuckley/cabot-search huggingface dataset:
End-of-life healthcare utilization among Medicare beneficiaries with malignant brain tumors.
Authors: Caleb Dulaney, Laura L Dover, Courtney Williams, Bradford E. Jackson, Paula Warren, John B. Fiveash, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2017)

244 Background: Patterns of end-of-life healthcare utilization for patients with primary and secondary malignant brain tumors (PMBT, SMBT) are poorly understood. The primary objective of this study was to compare end-of-life healthcare utilization and expenditures between patients with PMBT and SMBT. The secondary objective was to determine risk factors for low-quality healthcare utilization at the end-of-life. Methods: We analyzed Medicare administrative claims data for decedents with a diagnosis of PMBT or SMBT within a community cancer network in the southeastern US from 2012-2015. Outcomes included hospital-based care (ED visit, hospitalization, and ICU admission), cancer therapy (chemo- or radiotherapy), hospice care, and total cost to Medicare in the last 30 days of life. We performed regression analyses to determine risk factors for each of the outcomes. Results: 1323 patients had a diagnosis of PMBT (383) or SMBT (940). Patients with SMBT received more hospital-based care (57% v 49%, p &lt; 0.01) and more cancer therapy (25% v 18%, p &lt; 0.01) than those with PMBT. Male gender (RR 1.28, p = 0.03) and decreasing age (RR 1.09, p = 0.02) were risk factors for PMBT and SMBT hospital-based care, respectively. While the majority of PMBT (81%) and SMBT patients (78%) utilized hospice care, those with SMBT were more likely to enroll ≤ 3 days prior to death (10% v 5%, p &lt; 0.01). Hospital-based care (RR 5.22, p &lt; 0.01 (PMBT); RR 5.24, p &lt; 0.01 (SMBT)), and non-white race (RR 1.59, p = 0.04 (PMBT); RR 1.56, p &lt; 0.01 (SMBT)) were risk factors for no hospice utilization. Mean expenditures in the last 30 days of life were similar between PMBT and SMBT ($8592 v $9964). Hospital-based care increased the average cost by $16,303 (PMBT, p&lt;0.001) and $13,132 (SMBT, p&lt;0.001). Conclusions: Hospitalization at the end-of-life is common in patients with PMBT or SMBT and is associated with lower rates of hospice care and increased expenditure.
THE EFFECT OF RUNNING NINE MARATHONS IN NINE DAYS ON PROPRIOCEPTION AND BALANCE
Authors: Nicola Relph, Katie Small, Adam Smith
Journal: British Journal of Sports Medicine (2017)

Background Multi-day running events are becoming increasingly popular with nonprofessional athletes. However, it is unknown how and when this type of event affects injury risk factors such as proprioception and balance. Objective To evaluate the effect of running one, five consecutive and nine consecutive marathons on joint position sense (JPS) and dynamic balance. Design Cross-sectional, observational study. Setting Sports-injury clinic. Participants 21 athletes completing the event (age 44.8±8.09 yrs, mass 74.4±13.14 kg, years running 10.4±7.39 yrs, average weekly mileage 44.8±12.09 miles) entered the study. Ten athletes completed the JPS testing and five athletes completed the dynamic balance testing. Assessment of Risk Factors Risk factors were assessed the day before the event (day zero) and then following completion of one (day one), five (day five) and nine (day nine) consecutive marathons. The independent variable was time. Main Outcome Measurements JPS error into flexion and extension, star-excursion balance test (SEBT) and number of injuries per runner. Results Friedman's ANOVAs indicated no effects of time on JPS into extension ( p= 0.94), dominant-leg anterior ( p =0.52) or posterior-lateral ( p =0.65) SEBT reach. JPS flexion error significantly decreased by 1.3° from day one to five ( p =0.032). Non-dominant leg anterior, posterior-medial and posterior-lateral SEBT reaches significantly decreased from day zero to nine by 0.09% ( p =0.043), 0.13% ( p =0.043) and 0.17% ( p =0.043) of leg length respectively. Dominant leg posterior-medial SEBT reach also significantly decreased by 0.12% of leg length ( p= 0.043) from day zero to nine. There were 4.2 injuries per runner. Conclusions The results suggest multi-day running events can cause over four lower limb injuries per runner and reduce dynamic balance ability. Nonprofessional athletes completing these events should be aware of this high injury occurrence and prepare appropriately. Injury prevention programmes incorporating dynamic balance may be recommended. However future studies with additional risk factors and larger sample sizes are needed to substantiate these findings.
Oxaliplatin (OXA) with weekly bolus 5-fluorouracil (FU) and low-dose leucovorin (ld-LV) in advanced colorectal cancer (ACRC) patients (pts): Report of safety and efficacy
Authors: M. Chacon, E. Wasserman, A. Guercovich, J. Öconnor, G. Giornelli, C. Coronado, M. Barugel, E. Roca, S. Carraro, R. Chacon
Journal: Journal of Clinical Oncology (2004)

3769 Background: OXA and infused FU plus LV (FOLFOX) has proved to be one of the most active regimens in ACRC. On going trials, adjuvant and metastatic setting, have hypothesized that OXA given with bolus FU plus LV would be equally active and safe as OXA combined with infusional FU regimens. Since OXA registration in our country, constrains related to cost and convenience prompt to develop schedules of OXA/bolus FU/ld-LV. Patients and methods: We assessed retrospectively a cohort of pts with ACRC treated with OXA 85 mg/m2 days 1 and 15 plus LV 20 mg/m2 followed by a 500 mg/m2 bolus dose of FU on days 1, 8, and 15 every 28 days. Data of safety and efficacy are presented. Results: Between 1996 and 2002, 273 pts were treated in two centers. Pts characteristics: median age 56 (22–79), male/female: 151/122, colon/rectum 199/74, median metastatic sites 1 (1–4), first line/second / third (%): 68/ 13/ 3 and 16% received after metastasis resection (R0). 1146 cycles (cy) were administered, median per patient 4 (1–11). Safety: the main grade 3–4 toxicities were (pts): gastrointestinal 28, hematological 18, allergies 2, sepsis 3 pts and severe neurotoxicity 12 pts (4,3%). Toxic deaths occurred in 3 pts (1%) Efficacy: objective response rate (ORR) and time related parameters are summarized as follows: 17 pts initially unresectable ACRC pts were rendered resectable after a 6 (2–11) median cy of treatment. Conclusions: OXA combined with bolus FU and ld-LV seems to be safe and effective. Next multicentre randomized trials will show the comparative value between OXA combined with bolus or infusional FU. No significant financial relationships to disclose.
Creating an educational quality improvement program for radiation oncology residents in McGill University.
Authors: Catherine Anne Pembroke, Alain Biron, Joanne Alfieri
Journal: Journal of Clinical Oncology (2017)

118 Background: Quality insurance (QI) is a pillar of good clinical governance and is at the centre of modern health care. The Royal College of Physicians and Surgeons of Canada CanMeds 2015 have now mandated that QI should be taught and the competencies assessed in all post-graduate residency programs. To our knowledge, this is the first attempt to create a post-graduate QI curriculum amongst radiation oncology trainees. We aim to describe the feasibility of introducing these professional skills which should be integral to every training program. Methods: A QI team has been created within the department of Radiation Oncology at McGill University consisting of a clinical fellow and 3 staff physicians. QI teaching will take place in a longitudinal manner with the mandatory curriculum divided into foundation, intermediate and advanced competencies depending on years of seniority. Teaching is delivered by a combination of two academic half days, consisting of didactic lectures and practical workshops, and self-directed online modules. Each resident during the intermediate years (PGY2-4) will complete a QI project in 9 months under the supervision of an attending physician. The resident will become well versed with QI tools and techniques by presenting their project at specific 3-monthly time points to their supervisor and QI team. In June we will host a QI day where a QI scholar will be invited to teach, each resident will present their project and merit prizes will be awarded. Formal mandatory assessments will take place with a combination of self-assessment, QI- knowledge based assessments (QI-KATs) and balanced score cards. Results: The curriculum has been developed with input from McGill University curriculum and assessment experts. This is a pilot program for the academic 2016/17 year. We are currently meeting our pre-defined milestones. The program will be formally evaluated and adapted to ensure sustainability. Conclusions: The QI skills gained will enable the individual to maintain the highest standards throughout their subsequent careers. A robust, interactive, sustainable curriculum will ensure that this is delivered effectively within radiation oncology and act as a model for all residency programmes.
Anisotropic tough double network hydrogel from fish collagen and its spontaneous in vivo bonding to bone
Authors: Md. Tariful Islam Mredha, Nobuto Kitamura, Takayuki Nonoyama, Susumu Wada, Keiko Goto, Xi Zhang, Tasuku Nakajima, Takayuki Kurokawa, Yasuaki Takagi, Kazunori Yasuda, Jian Ping Gong
Journal: Biomaterials (2017)
High expression of epithelial-mesenchymal transition (EMT) markers in malignant mesothelioma and possible therapeutic intervention using an N-cadherin antagonist.
Authors: Milind Suraokar, Dan Dan He, Gabriela Mendoza, Norma Llansa, Denise Woods, Ludmila Prudkin, Ignacio Wistuba, Anne Tsao
Journal: Cancer Research (2008)

2816  Epithelial-mesenchymal transition (EMT) regulates metastatic progression in neoplastic tissue and may have an important carcinogenic role in malignant pleural mesothelioma (MPM). MPM tumors arise from mesothelial cells and could display either epithelial, mesenchymal, or sometimes both of these phenotypes. We tested the hypothesis that EMT plays an integral role in the pathogenesis of MPM by investigating the immunohistochemical (IHC) expression of 6 EMT-specific biomarkers in archival MPM tumors, verified the protein expression in MPM cell lines via Western blot analysis, and also conducted IC50 assays on MPM cell lines using three novel N-cadherin antagonists (ADH-1, ADH-200024, ADH-200718). The IHC analysis was performed on a tissue microarray constructed from 88 paraffin-embedded MPM tissues, which included 27 biphasic, 51 epitheloid and 10 sarcomatoid subtypes. MPM frequently expressed high levels of cytoplasmic and membrane β-catenin (64% of cases), membrane N-cadherin (47%), nuclear Snail (75%), and cytoplasmic vimentin (82%). Matrix metalloproteinase-9 (MMP-9, 12%) and integrin- α νβ6 (17%) showed high IHC expression at the cytoplasmic level in a small subset of tumors. Western blot analysis confirmed that most of these markers are expressed in mesothelioma cell lines e.g. Met5A, NC1-H28, MSTO-211H, NC1-H2052 and NC1-H2452. Reduced expression of E-cadherin protein was seen in MSTO-211H cells with a corresponding increase in N-cadherin protein. Our preliminary cell viability assays on the above-mentioned mesothelioma cell lines showed IC50 value ranges for ADH-1 (1.3 mM - 9.7 mM), ADH-200024 (0.2 mM - 1.6 mM), and ADH-200718 (13 nM - 84 nM). Conclusion: EMT-specific biomarkers have high expression levels in MPM tumors and are a potential target for cancer therapy. Further studies, with a focus on distinguishing differences between the three histologic subtypes, are currently underway. ADH-200718 may have viable antitumor activity against MPM cell lines.
Selection of the highly replicative and partially multidrug resistant rtS78T HBV polymerase mutation during TDF-ETV combination therapy
Authors: Elham Shirvani-Dastgerdi, Benjamin Y. Winer, Toni Celià-Terrassa, Yibin Kang, David Tabernero, Eray Yagmur, Francisco Rodríguez-Frías, Josep Gregori, Tom Luedde, Christian Trautwein, Alexander Ploss, Frank Tacke
Journal: Journal of Hepatology (2017)
Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing
Authors: Piul S. Rabbani, Anna Zhou, Zachary M. Borab, Joseph A. Frezzo, Nikita Srivastava, Haresh T. More, William J. Rifkin, Joshua A. David, Samuel J. Berens, Raymond Chen, Sophia Hameedi, Muhammad H. Junejo, Camille Kim, Rita A. Sartor, Che F. Liu, Pierre B. Saadeh, Jin K. Montclare, Daniel J. Ceradini
Journal: Biomaterials (2017)
Molecular analysis of non-epithelial ovarian cancer by histologic subtype.
Authors: Maise Al Bakir, Lei Wang, Kenneth Russell, Christina Fotopoulou, Robert C. F. Leonard, Sherri Z. Millis, Zoran Gatalica, Andreas Voss, Hani Gabra
Journal: Journal of Clinical Oncology (2014)

5570 Background: Non-epithelial malignancies of the ovary account for <2%–4% of all ovarian tumors. The classification of non-epithelial ovarian cancer can be broadly divided into two histological subtypes, ovarian germ cell tumors (OGCTs) and ovarian sex cord stromal tumors (OSCSTs). Molecular phenotypes of these groupings may identify genetic susceptibilities to existing therapies and thus improve patient care. Methods: 275 non-epithelial ovarian cancers (non-EOC) were profiled by Caris Life Sciences between 2009 and 2013 using a multiplatform approach. Within this cohort, patients could be further grouped according to histopathological subtypes, particularly OGCTs (n=42) and OSCSTs (n=217). Testing of FFPE tissues included a combination of sequencing (Sanger, NGS and pyrosequencing), protein expression (IHC), gene amplification (CISH or FISH), and/or RNA fragment analysis. Results: Of interest, the frequency of positive hormone receptor over-expression was higher in OSCSTs than OGCTs(AR 76%v 0%, PR 90% v 12%, ER 12% v 0%). Granulosa Cell tumors (n=173) were particularly strongly expressing for AR (81.7%), PR (95.9%) but not for ER (9.3%), with Alk, APC, and ATM mutations occurring rarely. Sertoli-leydig tumors (n=25) were characterized by high Topo2A (66.7%), TUBB3 (65%), BRAF (14.3%) and kras (20%) mutation, with lower AR (38%) and PR (60%) and higher ER (28%) expression than granulosa cell tumors. OGCT (n=42) cohorts exhibited RRM1 (51%), TLE3 (55%), TOP2A (87%), TUBB3 (51%), PTEN loss (67%) with mutations of P53 (56%) and PI3K (22%) also occurring. Kras mutation was observed in 1 of 9 OGCTs tested. Conclusions: Tumor profiling has identified molecular differences between non-EOC histological subtypes, by both expression and NGS mutational approaches in FFPE tissues. Identification of these changes can provide a rationale for treatment options not routinely considered or those associated with targeted therapies and warrant future clinical trials in this cancer type
Drug interactions in cancer inpatients
Authors: R. P. Riechelmann, Ó. Smaletz, E. D. Saad
Journal: Journal of Clinical Oncology (2004)

8146 Background: Patients with advanced cancer usually receive various classes of drugs. Although little has been published on this subject, there seems to be general consensus that drug interactions are associated with the number of medications a patient receives. We attempted to quantify the frequency of potential drug interactions not related to chemotherapy in our institution. Methods: Charts of 100 consecutive cancer patients who had been admitted between May and October 2003 were reviewed. Patients were excluded if they received chemotherapy and/or hormone therapy during hospital stay. Patients could have only one monthly admission analyzed. All drugs in the orders were tabulated, irrespective of whether they were actually administered. Interactions were screened with Drug Interaction Facts softwear and manually by the authors. Potential interactions were graded by their levels of severity (severe, moderate, and minor) and significance (1 to 5, with 1 representing the highest level of evidence).Results: Median age, length of stay and number of prescribed drugs per patient were 67 years (range, 20 to 94 years), 6 days (range, from less than one to 81 days), and 8 drugs (range, one to 20 drugs), respectively. 180 potential interactions were detected, with a median of one per patient per admission (range, none to 11 interactions). Of 100 patients, 63 presented any potential interaction, of which 18.3% were classified as severe, 56.7% as moderate, and 25% as minor. Approximately 7%, 18%, 13%, 52%, and 11% of potential interactions were graded as level 1, 2, 3, 4, and 5, respectively. Univariate analyses demonstrated that age (P=0.026), number of medications (P<0.0001) and length of stay (P=0.001) were correlated with potential interactions. In multivariate analysis, prescriptions with 5 or more drugs (risk ratio of 6.4, 95% CI: 1.82 to 22.56; P=0.004) and hospital stay of 7 or more days (risk ratio of 3.4, 95% CI:1.23 to 9.46; P=0.019) remained independently associated with potential interactions.Conclusions: Potential drug interactions are common among inpatients with advanced cancer. Length of hospital stay and number of prescribed drugs were risk factors in multivariated analyses. No significant financial relationships to disclose.
NO ASSOCIATION BETWEEN STATIC AND DYNAMIC POSTURAL CONTROL AND ACL INJURY RISK AMONG FEMALE ELITE HANDBALL AND FOOTBALL PLAYERS
Authors: Kathrin Steffen, Agnethe Nilstad, Tron Krosshaug, Kati Pasanen, Roald Bahr
Journal: British Journal of Sports Medicine (2017)

Background Little research exists quantifying balance measures as potential risk factors for ACL injury. Objective To assess whether static and dynamic postural control were associated with an increased risk for ACL injury in female elite handball and football players. Design Prospective cohort study. Participants From 2007 through 2015, 838 female premier league players participated in pre-season testing and were prospectively followed for ACL injury risk. Assessment of risk factors and main outcome measures At baseline, we recorded player demographics, playing experience, ACL and ankle injury history. We measured the mean velocity of COP in medio-lateral (ML) and anterior-posterior (AP) directions (mm/s), as well as the area of the 95% confidence ellipse area (mm 2 ). We used the Star Excursion Balance Test to measure anteromedial, medial and posteromedial reach directions (cm). To examine the stability of postural control measures over time, we examined long-term and short-term reproducibility. We followed a pre-defined statistical protocol with logistic regression models, one for each of the proposed risk factors. Results A total of 55 (6.6%) players (age: 20±4 yrs; height: 171±7 cm; body mass: 68±9 kg) sustained a non-contact ACL injury after baseline testing (1.8±1.8 yrs). When comparing height and leg-length normalized balance measures between injured and uninjured players in univariate analyses, none of the variables were statistically associated with an increased risk of ACL rupture. Short- and long-term reproducibility of the selected variables was poor. Players with a previous ACL injury had a 3-fold higher risk of sustaining a new ACL injury compared to previously uninjured players (OR 2.9, CI 1.4 to 5.7). Conclusions None of the static and dynamic postural control measures examined were associated with increased ACL injury risk among female elite handball and football players. Hence, the variables included in the current investigation cannot be used to predict injury risk.
Efficacy and safety of quizartinib (AC220) in patients age ≥ 70 years with FLT3-ITD positive or negative relapsed/refractory acute myeloid leukemia (AML).
Authors: Alexander E. Perl, Hartmut Dohner, Philippe H. Rousselot, Jean-Pierre Marie, Giovanni Martinelli, Neil P. Shah, Mark J. Levis, Guy Gammon, Denise Trone, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2013)

7023 Background: Advanced age and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in AML are each associated with early relapse after standard chemotherapy and poor survival. Quizartinib, an oral FLT3 inhibitor active against ITD mutant and wild type FLT3, has shown promising activity in Ph 1 and 2 studies. Methods: We provide detailed analysis from a Ph 2 study (N = 333) of quizartinib monotherapy, focusing on patients (pts) aged ≥ 70 y with AML that relapsed and/or was refractory to prior therapy. Results: A total of 83 pts age ≥70 y included 60 (72%) FLT3-ITD(+) and 23 (28%) FLT3-ITD(-). Median duration of treatment was 14.6 wks for FLT3-ITD(+) pts and 5.9 wks for FLT3-ITD(-) pts. Composite complete remission (CRc) rate included complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematologic recovery (CRi). Of 60 FLT3-ITD(+) pts, 32 (53%) had a CRc (1 CR, 3 CRp, 28 CRi). Of 23 FLT3-ITD(-) pts, 10 (43%) had a CRc (2 CR, 1 CRp, 7 CRi). 12/27 FLT3-ITD(+) pts (44%) and 5/10 FLT3-ITD(-) pts (50%) refractory to prior therapy responded to quizartinib, and 12/83 (14%) survived &gt;1 y. The most common (≥10%) Grade 3 or 4 treatment-related adverse events (TRAEs) were febrile neutropenia (22%), anemia (20%), transient QT interval prolongation (17%; no Grade 4), and thrombocytopenia (12%). 15 pts (18%) had TRAEs resulting in discontinuation. Conclusions: Because AML in the elderly, particularly in those aged ≥70 y, is genetically heterogeneous and often follows a myelodysplastic syndrome, there is a wide assumption that it may be less amenable to FLT3-targeted therapy than AML in younger pts. Our data argue against these conclusions and show that pts aged ≥70 y with chemotherapy-resistant AML have preserved high response rates, and promising survival to quizartinib. Clinical trial information: NCT00989261. [Table: see text]