tbuckley/cabot-search huggingface dataset:
IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy
Authors: Heather M. Gibson, Brooke N. McKnight, Agnes Malysa, Greg Dyson, Wendy N. Wiesend, Claire E. McCarthy, Joyce Reyes, Wei-Zen Wei, Nerissa T. Viola-Villegas
Journal: Cancer Research (2018)

Abstract IFNγ is an attractive target for imaging active antitumor immunity due to its function in the T-cell signaling axis. Here, we test an IFNγ immuno-PET (immunoPET) probe for its capacity to identify adaptive immunotherapy response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFNγ immunoPET detected elevated cytokine levels in situ after vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy. In a model of induced T-cell anergy where CD8 T cells infiltrate the tumor, but upregulate PD-1, IFNγ tracer uptake was equivalent to isotype control, illustrating a lack of antitumor T-cell activity. The IFNγ immunoPET tracer detected IFNγ protein sequestered on the surface of tumor cells, likely in complex with the IFNγ receptor, which may explain imaging localization of this soluble factor in vivo. Collectively, we find that the activation status of cytotoxic T cells is annotated by IFNγ immunoPET, with reduced off-target binding to secondary lymphoid tissues compared with imaging total CD3+ tumor-infiltrating lymphocytes. Targeting of soluble cytokines such as IFNγ by PET imaging may provide valuable noninvasive insight into the function of immune cells in situ. Significance: This study presents a novel approach to monitor therapeutic outcomes via IFNγ-targeted positron emission tomography. Cancer Res; 78(19); 5706–17. ©2018 AACR.
Assessing the appropriate utilization of the palliative care service by the Carol and Ray Neag Comprehensive Cancer Center at UConn Health.
Authors: Trena Stoute, Sarah Loschiavo, Karen Hook
Journal: Journal of Clinical Oncology (2018)

144 Background: The American Society of Clinical Oncology recommends initiation of palliative care concurrently with active treatment within 8 weeks of advanced cancer diagnoses. We studied the referral practice in our institution. Methods: We reviewed charts of all outpatients seen between June and November 2017 with a diagnosis of leukemia or breast, thoracic, head and neck, pancreas, and prostate malignancies. Data collection included: diagnosis, stage, age, race, gender, deceased/alive, lines of therapy, referral to palliative care, time to referral, reason for referral, time from referral to death, referring provider, inpatient/outpatient, follow up visits, hospitalizations, time from chemotherapy to death, referral for services, social worker referral, and insurance type. Patients with incomplete records were excluded. Fisher’s exact test and Wilcoxon rank-sum test were used to compare groups. Results: Of the 174 eligible patients, 49 (28%) were referred to Palliative Care. Only 22% of patients were referred within 8 weeks of diagnosis. The most common reason for referral was pain management; with the least common being goals of care. Women were more likely to be referred than men, 38% vs 22% (p = 0.035). The mean [SD] age was 63.9[14.7] years. By stage, 96% of patients had stage IV disease and the only stage III patients were those with lung cancer. Amongst stage IV cancers, breast and lung cancer had the highest referral rate, each 50%, with prostate cancer having the lowest at 5% (p &lt; 0.001); despite prostate cancer being the most common diagnosis. There were more referrals to hospice (24% vs 6%; p = 0.002) and home palliative care (16% vs 1%; p &lt; 0.001) in the group referred. The mean [SD] time (weeks) from last chemotherapy to death was shorter in the group referred 6.51[4.19] vs. 16.3 [11.29] (p = 0.037). There was no difference in referral rates to home care (p = 0.192), based on insurance type (p = 0.683) or race (p = 0.647). Conclusions: Referral rates in this analysis did not achieve the recommended guideline standards. Additional educational interventions are planned to identify and overcome barriers to referral.
Response to “Questions arising on phlebotomy in polycythemia vera: prophylactic measures to reduce thromboembolic events require patient-focused decisions” by Heidel et al.
Authors: Giovanni Barosi, Francesco Passamonti, Patrizia Accorsi, Fabrizio Pane, Alessandro M. Vannucchi, Claudio Velati, Robert Peter Gale, Sante Tura, Tiziano Barbui
Journal: Leukemia (2018)
Practice based pharmacists free up five hours of GP time a week
Authors: Ingrid Torjesen
Journal: BMJ (2018)

A clinical pharmacist based in a GP practice frees up almost five hours of GP time per week just by taking on prescribing work, a small study of practices in Scotland has found.1 They also improve patient safety and staff morale, and reduce stress levels in the practice, according to surveys of GPs and practice staff.

Clinical pharmacists in general practice was proposed as a way of reducing GP workload and improving patient care. In …
Understanding epidermal growth factor receptor mutation (<i>EGFR</i>m) testing in patients (pts) with non-small cell lung cancer (NSCLC) in a large community oncology network.
Authors: Eric Nadler, Ancilla Fernandes, Melissa Pavilack, Susan Amirian, Jamyia Clark, Jennifer R. Frytak
Journal: Journal of Clinical Oncology (2018)

9 Background: EGFR TKI therapy improves outcomes in pts with EGFRm+ NSCLC. NCCN guidelines recommend EGFRm testing for pts with NSCLC. Testing patterns and predictors of documented EGFRm testing were studied in a real-world setting. Methods: Adult pts with stage IV NSCLC treated from 1/1/2012 to 8/31/2017, identified from the iKnowMed (US Oncology Network) EHR were analyzed. Rates of documented EGFRm testing were calculated. Multivariable stepwise logistic regression analysis was conducted to identify characteristics associated with documented EGFRm testing. Results: Of 14,461 pts, 59.8% had adenocarcinoma and 17.5% had squamous cell carcinoma. Median age of pts was 69.3 years, 52.3% were male, and 14.6% were non-smokers. Testing rates were ~36% overall, an increase in rates was seen over time: ~30% in 2012 to 41% in 2016 (p &lt; .001). Histology, practice size, and several characteristics were associated with documented EGFRm testing (Table). Conclusions: Testing rates steadily increased over time, but were still low, implying suboptimal/under-documented testing. This analysis presents practice site characteristics to target educational programs to improve testing and/or documentation in community settings. [Table: see text]
Trust but verify: Patterns of obtaining health information and the role of physician trust in decision-making amongst patients with metastatic breast cancer.
Authors: Soumya J. Niranjan, Audrey S. Wallace, Beverly R Williams, Yasemin E. Turkman, Courtney Williams, Andres Forero-Torres, Smita Bhatia, Sara J. Knight, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2018)

218 Background: Increasing emphasis on patient-centered care has led to shared decision making, which better aligns medical decisions with patient preferences for care. In its 2004 report, Health Literacy: A Prescription to End Confusion, the US Institute of Medicine defines health literacy as the degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions. However, little is known about the confluent role of patient health information seeking patterns and physician trust in the decision-making process. Therefore, we assessed perspectives of metastatic breast cancer (MBC) patients and health care professionals regarding how health information seeking and physician trust influence decision making. Methods: Qualitative interviews with 26 MBC patients and 6 community oncologists, as well as 3 separate focus groups involving lay navigators, nurses, and academic oncologists, were recorded and transcribed. Qualitative data analysis was conducted using a content analysis approach that included a constant comparative method to generate themes from the transcribed textual data. Results: Five prominent themes emerged from these responses. (1) Patients’ primary source of treatment information were physicians. (2) Patients differed in their approach to seeking further health information regarding the discussed treatment options (e.g. internet websites, family and friends, support groups). (3) Patients trusted their physician’s recommendations to achieve their goals of care. (4) Oncologists were cognizant of their fundamental role in facilitating informed decision making (5) Patient and physician discordant perspectives on shared decision making were apparent. Conclusions: Patient procurement of health information and their capacity to use it effectively to make informed decisions in conjunction with their trust in physicians, may play an important role in shared decision making.
Abstract 19656: Optimal Stage for Intravenous Administration of Cardiac Stem Cells in Univentricular Heart Disease; Experimental Studies in Novel Swine Models of Single Ventricular Circulation
Authors: Takuya Goto, Daiki Ousaka, Toshikazu Sano, Kenta Hirai, Shingo Kasahara, Hidemasa Oh
Journal: Circulation (2017)

Introduction: We have recently reported that transcoronary infusion of cardiosphere-derived cells (CDCs) may improve cardiac function after staged palliation in patients with single ventricle physi...
Abstract 14338: Fast Degrading Tissue-Engineered Vascular Graft With High Cellular Infiltration Inhibits Calcification of the Graft
Authors: Tadahisa Sugiura, Shuhei Tara, Hidetaka Nakayama, Tai Yi, Yong-Ung Lee, Hideki Miyachi, Takuma Fukunishi, Christopher K Breuer, Toshiharu Shinoka
Journal: Circulation (2015)

Introduction: Tissue-engineered vascular grafts (TEVGs) are biologically active grafts which are entirely reconstituted by host-derived cells over an inflammation-mediated degradation process. Calcification of the graft is a detrimental condition that can severely impact graft performance. Therefore, preventing graft calcification is of great importance to success of arterial TEVGs. Hypothesis: We assessed the hypothesis that the fast degrading TEVGs with high cellular infiltration into the scaffold could inhibit calcification of the grafts. Methods: We created two versions of aortic TEVGs: 1) Slow Degrading (SD) group and 2) Fast Degrading (FD) group. Both groups had the same inner layer composed of a 50:50 poly (l-lactic-co- ε -caprolactone) copolymer (PLCL) scaffold. However, the outer layer of the SD group was composed of a poly (l-lactic acid) (PLA) nano-fiber whereas the outer layer of the FD group was composed of a combination of PLA and polyglycolic acid (PGA) nano-fiber. The PGA in the outer layer of the FD group will degrade around 2-4 weeks after implantation, which will let more inflammatory cells infiltrate the scaffold than in the SD group. Both TEVGs were implanted in 8-10 week old female mice (n = 10 in each group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks. Results: In the SD group, acute thrombosis occurred in two mice. Von Kossa staining showed calcification of the scaffold in 6 out of 8 grafts in the SD group, but none in the FD group (Fig. A). The cell number in the outer layer of the FD group was significantly higher than in the SD group (2.65 ± 1.91 x 10 3 /mm 2 vs. 0.87 ± 0.65 x 10 3 /mm 2 , FD group and SD group, respectively, p =0.02); no significant difference was observed in the inner layer (1.80 ± 0.53 x 10 3 /mm 2 vs. 1.75 ± 0.60 x 10 3 /mm 2 , FD group and SD group, respectively, p =0.85) (Fig. A, B). Conclusions: In conclusion the fast degrading TEVG with high cellular infiltration inhibited calcification of the grafts.
Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study
Authors: Fabrice Barlesi, Johan Vansteenkiste, David Spigel, Hidenobu Ishii, Marina Garassino, Filippo de Marinis, Mustafa Özgüroğlu, Aleksandra Szczesna, Andreas Polychronis, Ruchan Uslu, Maciej Krzakowski, Jong-Seok Lee, Luana Calabrò, Osvaldo Arén Frontera, Barbara Ellers-Lenz, Marcis Bajars, Mary Ruisi, Keunchil Park
Journal: The Lancet Oncology (2018)
Antibiotic Treatment for Uncomplicated Appendicitis Really Works
Authors: Edward H. Livingston
Journal: JAMA (2018)

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Abstract 19173: Effect of Adjunct Vitamin D Therapy on Vascular Function in African-Americans With Poorly Controlled Hypertension and Hypertensive Heart Disease
Authors: Naveen Trehan, Joseph Miller, Aaron Brody, Phillip Levy
Journal: Circulation (2017)

Introduction: Vitamin D deficiency has been associated with adverse vascular function including central aortic pressure (CAP), augmentation index (AI) and pulse wave velocity (PWV) in observational...
Abstract 19965: Metabolomic Signature of Fermented Milk Consumption Linked With Lower Prevalence of First-diagnosed, Stable Coronary Artery Disease
Authors: Andrej Teren, Frank Beutner, Anika Vogel, Uta Ceglarek, Markus Scholz, Gerhard Schuler, Joachim Thiery
Journal: Circulation (2015)

Introduction: Currently available epidemiologic studies examining the potential cardiovascular effects of milk and fermented milk products (FMP) are conflicting. Hypothesis: We aimed to assess the metabolomic signature of milk-containing nutrients, intake of which associates with the extent of stable coronary artery disease (CAD). Methods: We recruited 1301 patients (median age 62 years [interquartile range: 53-69]; men 809 [62.2%]) admitted for suspected stable CAD. Prior to coronary angiography, all patients answered a validated semi-quantitative Food-Frequency-Questionnaire. In addition, venous blood was collected from each patient for whole blood metabolomic analysis of 26 amino acids and 26 acylcarnitines, applying the targeted mass-spectrometry-based method. Obstructive CAD (obCAD) was represented by ≥ 1 coronary stenosis &gt; 50%. Non-obstructive CAD (nobCAD) was defined by angiographic presence of coronary atherosclerosis without any coronary stenosis &gt; 50%. Results: Patients with obCAD (n =515) showed lower median FMP intake (134.5 g/die [IQR: 83.1-214.5]) than patients with nobCAD (n=264; 150.7 g/die [IQR: 78.8-257.0]; p&lt;0.001), and patients with no CAD (n=522; 168.2 g/die [IQR: 101.2-265.9; p&lt;0.001]), respectively. We found no between-group difference in average milk intake (obCAD: 27.9 g/die [IQR: 3.2-93.1]; nobCAD: 27.5 g/die [IQR: 4.1-95.0]; no CAD: 40.4 g/die [IQR: 4.5-94.7]; NS). When considering each subgroup of FMP separately, higher yoghurt intake was in inverse, independent association with prevalence of obCAD (OR 95%CI: 0.867 [0.774-0.970]; p=0.002), and nobCAD + obCAD (OR 95%CI: 0.876 [0.785-0.978]; p=0.018), respectively. Upon adjustment for relevant confounder, increased FMP consumption correlated with lower blood concentrations of acylcarnitines (r= -0.062; p=0.032); in particular C2 (r= -0.105; p&lt;0.001), C4 (r= -0.082; p=0.004), C4OH (r= -0.070; p=0.013), C5 (r= -0.072; p=0.015), C8 (r= -0.069; p=0.017), and C141 (r= -0.097; p=0.001). Conclusion: Increased consumption of fermented milk was linked with lower prevalence of stable coronary artery disease and associated with decreased blood concentrations of short- and medium-chain saturated, and long-chain monounsaturated fatty acids.
GP receives formal warning after texting patient for “pub lunch”
Authors: Clare Dyer
Journal: BMJ (2018)

A GP who accessed a patient’s medical records for contact information, then texted her to suggest a “pub lunch,” has received a formal warning after a medical practitioners’ tribunal concluded that his fitness to practise was not impaired.

Richard Dean, 58, was working as a locum GP at the Avenue Surgery in Cirencester when he saw the patient, an aid worker. Dean, who does extensive voluntary work with refugees, obtained her number from her records and contacted her with his own mobile phone. He suggested that they meet for a pub lunch, adding that he “would love to know more” about her work.

The patient was “surprised and perturbed,” the tribunal heard, and complained to the practice, saying she was thinking …
Understanding health-related quality of life (HRQoL) in unresected stage III non-small cell lung cancer (NSCLC).
Authors: Kellie Ryan, Karen E Skinner, Ancilla Fernandes, Mark S. Walker, Melissa Pavilack, Rajeshwari S Punekar, Noam Avraham VanderWalde
Journal: Journal of Clinical Oncology (2018)

189 Background: Despite curative treatment intent, most patients (pts) with unresected Stage III NSCLC progress to metastatic disease. Prior research has shown significant benefits on clinical outcomes when HRQoL is assessed in clinical care, but understanding is limited in Stage III NSCLC. Methods: A retrospective review of community oncology medical records was conducted to examine real-world clinical outcomes such as overall and progression-free survival. Eligible pts were adults diagnosed from 1/1/2011 to 3/1/2016 with unresected Stage III NSCLC. In a subset of patients with available data, HRQoL was assessed using the 86-item Patient Care Monitor (PCM), a patient reported measure. Linear mixed models (LMM) were used to assess the impact of pt characteristics and change in PCM scores associated with progression. Results: The main sample included 478 pts: mean [SD] age was 67 [10] years, 55% male, 72% Caucasian, and 71.1% initially treated with concurrent chemoradiation. HRQoL analysis included 167 pts. LMM showed significant worsening of Index scores for General Physical Symptoms, Treatment Side Effects, Despair, and Impaired Ambulation (p &lt; 0.001) as well as Acute Distress (p = 0.044) at progression. Of the six symptoms analyzed, significant worsening of scores at progression occurred in pain, difficulty breathing, and fatigue (p &lt; 0.001). HRQoL consistently worsened at progression, but the pattern of severity for Index scores varied when separately evaluated in the pre- and post-progression periods. Symptom patterns showed improvement for Treatment Side Effects, Acute Distress, and Despair during the pre-progression period, but worsened post-progression, an effect that exceeded the pre-progression improvement. Receipt of radiation and increasing age were associated with better overall HRQoL; HRQoL tended to be worse in pts with greater comorbidity burden and impaired performance status. Conclusions: Our study demonstrated a pattern of clinically meaningful worsening of HRQoL at progression, with pts reporting worsening physical symptoms and negative psychological states. The results also appear consistent with clinical expectations and show HRQoL benefit of radiation therapy.
Abstract 19997: Contrasting Regulatory Functions of Coronary Arterial Kvβ Subunits in Metabolic Hyperemia
Authors: Matthew A Nystoriak, Vahagn Ohanyan, William M Chilian, Aruni Bhatnagar
Journal: Circulation (2016)

Introduction: Sustained heart function requires high fidelity coupling between myocardial O2 consumption and coronary blood flow. Metabolic cues trigger hyperpolarization and relaxation of coronary...
Representativeness of oncology clinical trials in Alberta.
Authors: Safiya Karim, Yuan Xu, Shiying Kong, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2018)

27 Background: The Institute of Medicine encourages broad participation by patients in clinical trials to “efficiently provide practice-changing evidence”. Enrolment of a representative sample of the general oncology population in clinical trials is essential to ensure that outcomes are generalizable and to ensure equity and social justice. Our aims were to 1) determine the characteristics of all cancer patients compared to those enrolled on a clinical trial and 2) to determine factors and outcomes associated with clinical trial participation. Methods: We assembled a large cohort of patients diagnosed with all solid malignancies between 2004 and 2016 in a large Canadian province. We collected information on age, sex, tumor type, Charlson comorbidity index (CCI), year of diagnosis, treatment type (surgery, chemo, radiation, and immunotherapy). Logistic regression was used to identify factors associated with clinical trial participation. Cox regression models were constructed to determine overall survival (OS). Results: We identified 146,294 patients with a cancer diagnosis, of which 43% were men and the mean age at diagnosis was 61 years (SD 15.6). Approximately 3% (4,364/146,294) of all patients were enrolled in a clinical trial. Baseline characteristics showed that clinical trial patients were younger (mean age 58 years vs 61 years), had fewer comorbidities (CCI 0 = 83% vs. 73%) and more often male (45% vs 43%). Compared to all patients, clinical trial patients were more likely to be younger (OR 0.98, p &lt; 0.001), male (OR 1.21, 95% CI 1.10-1.32 p &lt; 0.001), and to have a diagnosis of brain (OR 3.8, 95% CI 2.86-5.05, p &lt; 0.001), kidney (OR 2.61, 95% CI 1.93-3.52) or breast cancer (OR 2.38, 95% CI 1.84-3.08). Compared to all patients and those not treated on clinical trial, patients on clinical trial had improved OS (HR 0.81, 95% CI 0.77-0.85, p &lt; 0.001). Conclusions: Only a small proportion of real world patients are treated within a clinical trial. Characteristics of clinical trials patients are significantly different from all patients with cancer. More representative clinical trials are needed in order to reflect the real world cancer population.
Abstract 13495: Efficacy of Intravenous Magnesium for Cardioversion of Atrial Fibrillation
Authors: Bharath Rajagopalan, Deepika Narasimha, Ashish Bhatia, Chee H Kim, Donald F Switzer, Anne B Curtis
Journal: Circulation (2014)

Background: Low serum magnesium (Mg) levels are associated with an increased risk of atrial fibrillation (AF). Intracellular deficiency of Mg has been demonstrated in patients with various supraven...
Methyltransferase Dot1l preferentially promotes innate IL-6 and IFN-β production by mediating H3K79me2/3 methylation in macrophages
Authors: Xiang Chen, Xingguang Liu, Yunkai Zhang, Wanwan Huai, Qingqing Zhou, Sheng Xu, Xi Chen, Nan Li, Xuetao Cao
Journal: Cellular and Molecular Immunology (2018)