tbuckley/cabot-search huggingface dataset:
Breast cancer survivors' self-reported outcomes following an end of treatment group intervention.
Authors: Genevieve Chaput, Maria Barrette, Vanessa DiLalla, Tristan Williams, Olivia Yu, AndreAnne Robitaille
Journal: Journal of Clinical Oncology (2018)

18 Background: The merit of supporting and educating breast cancer survivors (BCS) about survivorship issues such as cognitive dysfunction, body image concerns and fear of recurrence following treatment completion is well recognized. Though the majority of BCS appear to adjust fairly well in the long term, the transition from active treatments to survivorship is often described as distressing. While individualized interventions are typically not sustainable, group interventions provide an opportunity to inform BCS about potential late and long-term effects from cancer treatments in a supportive environment. BCS were offered an end of treatment educational group intervention (EOT). The EOT consists of a survivorship education session delivered by an MD and RN, a kit containing patient resources, as well as a survivorship care plan (SCP). BCS caregivers are welcomed to attend the EOT. This study aimed to assess BCS’ satisfaction, confidence level in managing their health, and intent to use the information received at the EOT. Methods: 18 EOTs have been provided to 83 BCS (group size range: 4 to 8 BCS, caregiver attendees not included). Participants completed a brief Likert-scale survey on a voluntary basis after the EOT. Variables of interest for included reported satisfaction, confidence and intent to use information received during the EOT. Descriptive statistics were utilized to analyze collected data. Results: Completed surveys were received from 69 participants (response rate 83.1%). To the survey question: “The survivorship information I received was helpful”, 72% (50) and 26% (18) responded strongly agreed and agreed, respectively. The majority of participants reported “Feeling better prepared for the next steps regarding their care” following the EOT (60% (42) strongly agreed; 33% (23) agreed). Lastly, the majority (78%) stated they were “very likely” to use the EOT information. Conclusions: Current evidence has demonstrated the feasibility and patient-related benefits of educational interventions within the field of survivorship. Our results suggest group-based interventions are efficient and effective for addressing the supportive and informational needs of BCS after treatment completion.
Tunable Elastomers with an Antithrombotic Component for Cardiovascular Applications
Authors: Alexander M. Stahl, Yunzhi Peter Yang
Journal: Advanced Healthcare Materials (2018)

Abstract This study reports the development of a novel family of biodegradable polyurethanes for use as tissue engineered cardiovascular scaffolds or blood‐contacting medical devices. Covalent incorporation of the antiplatelet agent dipyridamole into biodegradable polycaprolactone‐based polyurethanes yields biocompatible materials with improved thromboresistance and tunable mechanical strength and elasticity. Altering the ratio of the dipyridamole to the diisocyanate linking unit and the polycaprolactone macromer enables control over both the drug content and the polymer cross‐link density. Covalent cross‐linking in the materials achieves significant elasticity and a tunable range of elastic moduli similar to that of native cardiovascular tissues. Interestingly, the cross‐link density of the polyurethanes is inversely related to the elastic modulus, an effect attributed to decreasing crystallinity in the more cross‐linked polymers. In vitro characterization shows that the antiplatelet agent is homogeneously distributed in the materials and is released slowly throughout the polymer degradation process. The drug‐containing polyurethanes support endothelial cell and vascular smooth muscle cell proliferation, while demonstrating reduced levels of platelet adhesion and activation, supporting their candidacy as promising substrates for cardiovascular tissue engineering.
miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy
Authors: Qian Huang, Jiajia Xia, Lei Wang, Xu Wang, Xiaodong Ma, Qipan Deng, Yong Lu, Munish Kumar, Zhiyuan Zhou, Ling Li, Zhaoyang Zeng, Ken H. Young, Qing Yi, Mingzhi Zhang, Yong Li
Journal: Journal of Hematology & Oncology (2018)

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer. Yet, the combination of IDO1 inhibition and CAR T has not been attempted.We analyze IDO1 downregulation by miR-153 in colon cancer cells and the association of IDO1 and miR-153 expression with colorectal patient survival. We generate CAR T cells targeting the epidermal growth factor receptor variant III and measure their tumor killing effects against colon cancer cells with or without miR-153 overexpression by killing assays and in xenografts.IDO1 is highly expressed in colorectal tumors and is inversely associated with patient survival. miR-153 directly inhibits IDO1 expression by targeting its 3' untranslated region in colon cancer cells; yet, miR-153 overexpression does not affect cancer cell survival, apoptosis, and colony formation. When colon cancer cells are targeted by CAR T cells, miR-153 overexpression within tumor cells significantly enhances T cell killing in vitro and suppresses xenograft tumor growth in mice.These findings indicate that miR-153 inhibits IDO1 expression in colon cancer cells and is a tumor-suppressive miRNA that enhances CAR T cell immunotherapy. This study supports the combinatorial use of IDO1 inhibitors and CAR T cells in treating solid tumors.
Exposure-adjusted adverse events (AEs) comparing blinatumomab to standard of care (SOC) chemotherapy in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) from a randomized phase III study.
Authors: Anthony Selwyn Stein, Richard A. Larson, Andre C. Schuh, William Stevenson, Ewa Lech-Maranda, Kun Nie, Zachary Franklin Zimmerman, William Kormany, Max S. Topp
Journal: Journal of Clinical Oncology (2017)

7032 Background: Blinatumomab (blin), a bispecific T-cell engaging antibody construct, has shown improved overall survival vs SOC in pts with r/r ALL in a randomized phase 3 study ( Haematologica 2016;101:S129). To better evaluate safety, we compared AEs of blin vs SOC after adjusting for varying treatment exposure times. Methods: Adults ≥ 18 yrs with r/r ALL (refractory, 1 st relapse &lt; 1 yr, ≥ 2 relapses or relapse after transplant) were randomized to receive blin or SOC (1 of 4 predefined regimens). Blin was dosed by continuous infusion (4 wks on/2 wks off) for up to 5 cycles (9 µg/d on d1−7 in cycle 1, then 28 µg/d); up to 4 maintenance cycles (4 wks on/8 wks off) were allowed for ≤ 12 mo. Exposure-adjusted (exp-adj) event rates were calculated as no. of events*100/total exposure time (Table). Results: Median (range) no. of cycles were 1 (1−4) for SOC and 2 (1−9) for blin. The highest exp-adj rates (per 100 pt-yrs) were for pyrexia (507 SOC vs 376 blin), anemia (987 vs 229), thrombocytopenia (750 vs 126) and neutropenia (351 vs 121), all lower in blin. Febrile neutropenia (365 vs 93) and infections (1216 vs 436) were also both lower in blin (p &lt; 0.0001). Exp-adj rates for neurologic events were 743 SOC vs 472 blin, with median time (range) to onset of 7 (1−43) d and 7 (1−190) d, respectively, and gr ≥ 3 cytokine release syndrome (CRS) rates were 0 SOC vs 10 blin. The most frequent AEs in both cycles 1 and 2 were pyrexia, nausea and anemia in both arms; CRS events decreased in the blin arm between cycles 1 and 2 (14% vs 2%). Most fatal AEs were related to infection in both arms. Conclusions: Here blin showed an AE profile consistent with that previously reported for r/r ALL, including similar rates of manageable CRS and neurologic events. Exp-adj AE rates were generally higher in SOC vs blin, including for cytopenias and infections. Clinical trial information: NCT02013167. [Table: see text]
Deferred treatment with sofosbuvir–velpatasvir–voxilaprevir for patients with chronic hepatitis C virus who were previously treated with an NS5A inhibitor: an open-label substudy of POLARIS-1
Authors: Marc Bourlière, Stuart C Gordon, Eugene R Schiff, Tram T Tran, Natarajan Ravendhran, Charles S Landis, Robert H Hyland, Luisa M Stamm, Jie Zhang, Hadas Dvory-Sobol, G Mani Subramanian, Diana M Brainard, John G McHutchison, Lawrence Serfaty, Alex J Thompson, Thomas E Sepe, Michael P Curry, K Rajender Reddy, Michael P Manns
Journal: The Lancet. Gastroenterology & hepatology (2018)
Abstract 10355: Physiologic Effect of Repeated Epinephrine Doses During Cardiopulmonary Resuscitation: A Randomized Porcine Study
Authors: Bjarne Madsen Härdig, Michael Götberg, Malin Rundgren, Matthias Götberg, David Zughaft, Robert Kopotic, Henrik Wagner
Journal: Circulation (2015)

Objectives and Method: This porcine study was designed to explore the effect of repetitive epinephrine (EPI) doses on physiologic parameters during CPR. Thirty-six adult pigs were randomized to four injections of: EPI 0.02 mg/kg/dose, EPI 0.03 mg/kg/dose or saline control, given during 15 minutes of CPR. The effect on systolic, diastolic and mean arterial blood pressures (ABP), cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), SpO2, cerebral tissue oximetry (SctO2), were analyzed immediately prior to each injection and at peak arterial systolic pressure. Arterial blood gases was analyzed after the baseline and after 15 min. Result: Prior to and following 4 minutes of baseline chest compressions without drug administration, there were no significant differences between the three groups. In the group given a 0.02 mg/kg/dose, there were increases in all ABP’s and CePP at the first 3 pressure peaks; at the 4th only mean ABP was increased. Decreased ETCO2 following peak 1 and beyond was seen. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg/kg/dose, all ABP’s and CePP increased at the first 3 pressure peaks. Lower ETCO2 was seen at peak 1 and beyond. SctO2 and SpO2 were lower following injection 2 and beyond. In the saline control group the systolic ABP was significantly lower at pressure peak 1 and beyond, no other parameter changed significantly compared to baseline. In the two EPI groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to control. Conclusion: Repetitive EPI doses increased ABP’s and CePP, but this did not translate into better organ or brain perfusion.
Abstract 215: Post Arrest Head CT Imaging: Commonly Done, but not a Determinant of Early Care Withdrawal
Authors: Aiham Albaeni, Shaker M Eid, Dhanajay Vaidya, Nisha Chandra-Strobos
Journal: Circulation (2013)

Background: The decision to perform head CT, following non-traumatic cardiac arrest, is based on clinical judgment. We examined whether such expensive testing, factored into early care decisions. Methods: We studied 202 out-of-hospital, non traumatic, cardiac arrest survivors and analyzed patients who had Head CT imaging performed within 72 hours of admission. Grossly abnormal results were defined as severe diffuse brain edema, herniation or bleeding. Demographics, cardiac arrest characteristics and hospital care were studied in patients with and without abnormal CT finding using Chi square and t test. Logistic regression was used to identify the impact of abnormal head CT findings on early care withdrawal. Results: Of 202 patients studied, 137 had CT imaging (67%). Of these 112 patients (81%) had an unremarkable (“normal”) head CT (group1) whereas 25 patients (18%) had abnormal head CT findings as described above (group2). Mean age for patients receiving a head CT was 61 years (SD±15).No obvious demographic feature emerged as a characteristic or a predictor of an abnormal head CT (PNS, Table1). An abnormal head CT prompted more family meetings, further neurological evaluation (all P&lt;0.05) but did not result in early care withdrawal {within 72 hours of admission} as compared to those with an unremarkable study [OR=1.2, 95% CI (0.4-3) P=0.64]. Conclusion: Although head CT is often performed post arrest, grossly abnormal findings are uncommonly found, and do not predict early care withdrawal. The clinical usefulness of this test in guiding decision making remains unclear and unsubstantiated.
Cluster analysis to demonstrate the need to individualize care for cancer survivors.
Authors: Belle Hadewijch de Rooij, Elyse R. Park, Giselle Katiria Perez, Julia Rabin, Katharine M. Quain, Don S. Dizon, Kathryn E. Post, Garrett Chinn, Allison McDonough, Rachel Jimenez, Lonneke V van de Poll-Franse, Jeffrey M. Peppercorn
Journal: Journal of Clinical Oncology (2018)

62 Background: In efforts to inform clinical screening and development of survivorship care services, we sought to characterize patterns of healthcare needs among cancer survivors by 1) identifying and characterizing subgroups of survivors based on self reported health care needs, and 2) assessing socio-demographic, clinical and psychosocial factors associated with these subgroups. Methods: We conducted a cross-sectional self administered survey among patients presenting for routine follow-up care for early stage cancer (breast, gynecologic, neuro, gastro-intestinal, genito-urinary, thoracic, head and neck, melanoma, sarcoma and hematologic) at our academic medical center. Latent class cluster analysis was used to identify clusters of survivors based on survivorship care needs within 7 domains (side-effects, lifestyle/self-care, emotional coping, social support, sexual health, complementary services and practical support). Multiple logistic regression analyses were used to assess factors associated with these clusters. Results: Among 292 respondents, the highest unmet needs were related to information regarding side effects (53%), lifestyle/self-care (51%) and emotional coping (43%) domains. Our analysis identified 4 clusters of survivors: 1) low needs (N = 123, 42%), 2) mainly physical needs (N = 46, 16%), 3) mainly psychological needs (N = 57, 20%) and 4) both physical and psychological needs (N = 66, 23%). Compared to cluster 1, those in clusters 2, 3, and 4 were younger (P &lt; 0.03); those in clusters 3 and 4 had higher levels of fear of recurrence, anxiety, depression and insomnia (P &lt; 0.05); and those in clusters 2 and 4 reported higher levels of fatigue (P &lt; 0.05). Conclusions: Unmet needs among cancer survivors are prevalent and must be addressed, however a substantial group of survivors report low or no healthcare needs. The wide variation in healthcare needs among cancer survivors suggests a need for screening all patients, followed by tailored interventions in clinical care delivery and research to improve outcomes.
Endogenous albumin-mediated delivery of redox-responsive paclitaxel-loaded micelles for targeted cancer therapy
Authors: Yujie Zhang, Zhongyuan Guo, Zhonglian Cao, Wenxi Zhou, Yu Zhang, Qinjun Chen, Yifei Lu, Xinli Chen, Qin Guo, Chao Li, Donghui Liang, Tao Sun, Chen Jiang
Journal: Biomaterials (2018)
High or low return to sport rates following hip arthroscopy is a matter of definition?
Authors: Tobias Wörner, Kristian Thorborg, Anders Stålman, Kate E Webster, Hanna Momatz Olsson, Frida Eek
Journal: British Journal of Sports Medicine (2018)

ObjectivesThe primary aim of this study was to describe return to sport (RTS) following hip arthroscopy (HA) for femoroacetabular impingement syndrome (FAIS).The secondary aim was to examine patient satisfaction with RTS-levels reached as well as to describe patient reported time to RTS. MethodsPatients operated for FAIS between 2014-2016 (n=208) were invited to respond to an online-survey.RTS was assessed on a continuum from (a) no return to sport or exercise, return to (b) different sport/exercise (c) same sport/exercise at lower performance-level (d) same sport/exercise at same performance-level.Time to RTS was defined as time between HA and return to previous (pre-symptomatic) sport or exercise ResultsThe final sample consisted of 127 patients (mean age: 34.3 years [SD=10.2);mean time post-HA=19.4months [SD=10.4]).In total, 89% of patients had returned to some sort of sport or exercise.However, only 50% returned to same sport [21.4% to same-and 28.3% to lower performance-levels] and 39% returned to participation in a different sport.Eleven percent had not returned to any form of sport/exercise. ConclusionsDefining RTS following HA as continuum revealed that only half of all patients returned to the same sports/exercise as prior to hip symptoms, and just a fifth reported a return to previous performance-levels.Hence, traditional definitions may yield overly optimistic results, and not reflect the complete RTS-picture needed for clinicians aiming to create realistic patient expectations.
Safety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors.
Authors: Paul Haluska, Michael E. Menefee, Elizabeth R. Plimack, Jonathan E. Rosenberg, Donald W. Northfelt, Theresa LaVallee, Wenmei Huang, Xiang-Qing Yu, Jaye Viner, Patricia LoRusso
Journal: Journal of Clinical Oncology (2012)

TPS2618 Background: MEDI-573 is an investigational dual-targeting human antibody that neutralizes IGF-I/-II ligands and inhibits IGF‑1R and insulin receptor-A (IR-A) signaling pathways. By sparing IR-B and its hybrid receptors, MEDI-573 may achieve antitumor activity without perturbing glucose homeostasis. Objectives of this phase 1 dose-escalation and expansion study are to evaluate safety and determine the maximum tolerated dose (MTD), optimal biologically effective dose, pharmacokinetics, pharmacodynamics, and immunogenicity of MEDI-573 in adult patients with solid tumors. Methods: Patients with advanced solid tumors, Karnofsky status ≥60, and adequate organ function were treated with escalating doses of MEDI-573 IV once weekly (0.5 to 15 mg/kg) or every 3 weeks (30 or 45 mg/kg q3w) using a 3+3 design. Three patients per dose level were evaluated for safety. A biomarker-rich dose-expansion arm tested weekly 5 or 15 mg/kg MEDI‑573 in patients with advanced bladder cancer. Results: Preliminary data are presented for 43 patients (25 M, 18 F), median age 64 years. No dose-limiting toxicities or serious toxicity patterns occurred at any dose level. Drug-related adverse events occurring in ≥10% of patients were fatigue (28%), decreased appetite (23%), nausea (16%), diarrhea (14%), and anemia (12%); the majority were ≤ grade 2. Perturbations in insulin and growth hormone were not observed. Clinically significant changes in serum glucose were rare. The MTD was not reached after completely enrolling patients through the highest dose, 45 mg/kg IV q3w. Serum exposure of MEDI-573 increased with increasing dose. Full suppression of IGF‑I/-II was achieved with weekly and q3w dosing. No neutralizing antibodies against MEDI‑573 were detected. Of 43 patients, 8 (19%) had stable disease ≥12 weeks. The longest exposure was 21 months in a patient with well-differentiated liposarcoma. Conclusions: MEDI-573 demonstrated an acceptable safety profile at all doses tested. No dose-limiting toxicity or serious toxicities, including those related to glucose homeostasis, were detected. These preliminary results support further clinical development.
The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study
Authors: Anand Srivastava, Ragnar Palsson, Arnaud D. Kaze, Margaret E. Chen, Polly Palacios, Venkata Sabbisetti, Rebecca A. Betensky, Theodore I. Steinman, Ravi I. Thadhani, Gearoid M. McMahon, Isaac E. Stillman, Helmut G. Rennke, Sushrut S. Waikar
Journal: Journal of the American Society of Nephrology (2018)

Background Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data.Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT).Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m2 During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27).Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.