tbuckley/cabot-search huggingface dataset:
Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial
Authors: Robert J. Canter, Steven K. Grossenbacher, Jennifer A. Foltz, Ian R. Sturgill, Jiwon S. Park, Jesus I. Luna, Michael S. Kent, William T. N. Culp, Mingyi Chen, Jaime F. Modiano, Arta M. Monjazeb, Dean A. Lee, William J. Murphy
Journal: Journal for ImmunoTherapy of Cancer (2017)

We have previously shown that radiotherapy (RT) augments natural killer (NK) functions in pre-clinical models of human and mouse cancers, including sarcomas. Since dogs are an excellent outbred model for immunotherapy studies, we sought to assess RT plus local autologous NK transfer in canine sarcomas.Dog NK cells (CD5dim, NKp46+) were isolated from PBMCs and expanded with irradiated K562-C9-mIL21 feeder cells and 100 IU/mL recombinant human IL-2. NK homing and cytotoxicity ± RT were evaluated using canine osteosarcoma tumor lines and dog patient-derived xenografts (PDX). In a first-in-dog clinical trial for spontaneous osteosarcoma, we evaluated RT and intra-tumoral autologous NK transfer.After 14 days, mean NK expansion and yield were 19.0-fold (±8.6) and 258.9(±76.1) ×106 cells, respectively. Post-RT, NK cytotoxicity increased in a dose-dependent fashion in vitro reaching ~ 80% at effector:target ratios of ≥10:1 (P < 0.001). In dog PDX models, allogeneic NK cells were cytotoxic in ex vivo killing assays and produced significant PDX tumor growth delay (P < 0.01) in vivo. After focal RT and intravenous NK transfer, we also observed significantly increased NK homing to tumors in vivo. Of 10 dogs with spontaneous osteosarcoma treated with focal RT and autologous NK transfer, 5 remain metastasis-free at the 6-month primary endpoint with resolution of suspicious pulmonary nodules in one patient. We also observed increased activation of circulating NK cells after treatment and persistence of labelled NK cells in vivo.NK cell homing and cytotoxicity are increased following RT in canine models of sarcoma. Results from a first-in-dog clinical trial are promising, including possible abscopal effects.
Clinical profile and outcomes of carcinoma anal canal: A single institution experience
Authors: D. Koppaka, K.C. Lakshmaiah, K.G. Babu, L. Dasappa, L.A. Jacob, M.C.S. Babu, K.N. Lokesh, A.H. Rudresha, L.K. Rajeev, S.C. Saldanha
Journal: Annals of Oncology (2017)
Modeling of quality of life in older adults with advanced cancer: Data from a URCC NCORP multisite trial.
Authors: Marie Anne Flannery, Eva Culakova, Huiwen Xu, Kah Poh Loh, Charles Stewart Kamen, Megan Wells, Jodi Geer, Mark Allen O'Rourke, Nicholas Vogelzang, William Dale, Paul Duberstein, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2017)

218 Background: While the importance of symptom assessment is well recognized in Palliative Care (PC), limited evidence is available on the growing population of older adults with advanced cancer. Increasingly geriatric assessment (GA), which incorporates validated tools to assess health status, is advocated as a component of the care for older patients with cancer, but is not routinely incorporated into PC evaluations. We tested the hypothesis that variability in QoL for older adults with advanced cancer would be predicted by both symptoms and GA. Methods: Data from an ongoing cluster RCT conducted at 68 oncology practices were analyzed. Inclusion criteria were: &gt; 70 years old, advanced solid tumor diagnosis, impairment in at least 1 GA domain (e.g., function). Multiple reliable and valid objective assessments and self-report measures for each GA domain were completed. Symptoms were assessed by MD Anderson Symptom Inventory (MDASI). Hierarchical regression modeling was conducted. The dependent variable was FACT score at Time 2 (4-6 weeks). The independent (Time 1) variables were entered in 3 steps: 1) gender, race, educational level( &lt; or &gt; high school), cancer type ( GI / Lung or other), receiving chemotherapy; 2) MDASI, 3) GA measures: Polypharmacy, Blessed Orientation and Memory Concentration Test, % weight loss, Short Physical Performance Battery, Instrumental Activities of Daily Living (IADL), Older Adult Resource Survey (OARS) Comorbidity, OARS Medical Social Support, and Generalized Anxiety Disorder-7. Results: N = 342 at time 1 (Mean age 77 years, 43% female, 90% white, 51% high school graduates, 49% GI or Lung cancer, 68% on chemotherapy). N = 303 at time 2(11% attrition due to death or withdrawal). Overall, 46% of variance in QoL was explained (demographic and disease characteristics: 4% [p = .05], symptoms: 32% [p &lt; .0001], GA measures: 10% [p &lt; .0001]). Significant individual GA predictors of worse QoL were lower social support, higher anxiety, impairment in IADLs, and poorer physical performance. Conclusions: Findings suggest that GA explains variance in quality of life scores for older adults with advanced cancer and reinforce the importance of symptom assessment and management in this population. Clinical trial information: NCT02107443.
Abstract 13510: No-reflow in Reperfused Myocardium Does Not Contribute to Final Infarct Size in Pigs
Authors: Andreas Skyschally, Petra Kleinbongard, Gerd Heusch
Journal: Circulation (2016)

The no-reflow phenomenon is a frequent complication in patients with reperfused acute myocardial infarction and associated with a worse prognosis. It is unclear whether cardioprotection, apart from infarct size (IS) reduction, has also a beneficial impact on the extent of no-reflow. In an anesthetized pig model of myocardial ischemia/reperfusion, we have now used established conditioning maneuvers as a tool to distinguish damage and protection from it in the myocardium, expressed as final IS, and in the coronary microcirculation, expressed as area of no-reflow (ANR). Myocardial ischemia was induced by transient occlusion of the left anterior descending coronary artery (LAD). Myocardial blood flow was measured with microspheres. Cardioprotection was induced by local ischemic preconditioning (IPC; n=10; 2 x 3 min LAD occlusion/2 min reperfusion 15 min prior to 60 min LAD occlusion), remote ischemic preconditioning (RIPC; n=10; 4x5 min hindlimb occlusion/reperfusion 90 min prior to 60 min LAD occlusion), or ischemic postconditioning (POCO; n=6; 4x1 min LAD re-occlusion/reperfusion at 1 min reperfusion after 60 min LAD occlusion). Pigs without protection (PLA; n=10) served as controls. After 180 min reperfusion, the ANR (intra-atrial injection of thioflavin S) and the area at risk (AAR; intra-atrial injection of blue dye with re-occluded LAD) were demarcated. IS was determined by post-mortem triphenyl-tretrazolium chloride (TTC) staining. The AAR and myocardial blood flow during ischemia were not different among groups. IS reduction was similar with IPC, RIPC, and POCO (PLA: 37±3% of AAR; IPC*: 21±3%; RIPC*: 17±2; POCO*: 24±5%; mean±SEM; *p&lt;0.05 vs. PLA). Only IPC and RIPC reduced the ANR (PLA: 28±4% of AAR; IPC*: 4±3%; RIPC* 9±2%), whereas POCO did not (24±5%). All conditioning maneuvers protected the myocardium, but the microcirculation was only protected by conditioning maneuvers applied prior to LAD occlusion. POCO’s protection of myocardium, but not coronary microcirculation might be related to different time frames or to different underlying mechanisms of injury and/or protection in the two compartments. Nevertheless, the remaining no-reflow observed with POCO did not result in greater infarction.
Functional Brain Imaging Updates on the Horizon
Authors: Jennifer Abbasi
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Tackler’s head position relative to the ball carrier is highly correlated with head and neck injuries in rugby
Authors: Shogo Sobue, Takayuki Kawasaki, Yoshinori Hasegawa, Yuki Shiota, Chihiro Ota, Takeshi Yoneda, Shigeyuki Tahara, Nobukazu Maki, Takahiro Matsuura, Masahiro Sekiguchi, Yoshiaki Itoigawa, Tomohiko Tateishi, Kazuo Kaneko
Journal: British Journal of Sports Medicine (2017)

To characterise the tackler's head position during one-on-one tackling in rugby and to determine the incidence of head, neck and shoulder injuries through analysis of game videos, injury records and a questionnaire completed by the tacklers themselves.We randomly selected 28 game videos featuring two university teams in competitions held in 2015 and 2016. Tackles were categorised according to tackler's head position. The 'pre-contact phase' was defined; its duration and the number of steps taken by the ball carrier prior to a tackle were evaluated.In total, 3970 tackles, including 317 (8.0%) with the tackler's head incorrectly positioned (ie, in front of the ball carrier) were examined. Thirty-two head, neck or shoulder injuries occurred for an injury incidence of 0.8% (32/3970). The incidence of injury in tackles with incorrect head positioning was 69.4/1000 tackles; the injury incidence with correct head positioning (ie, behind or to one side of the ball carrier) was 2.7/1000 tackles. Concussions, neck injuries, 'stingers' and nasal fractures occurred significantly more often during tackles with incorrect head positioning than during tackles with correct head positioning. Significantly fewer steps were taken before tackles with incorrect head positioning that resulted in injury than before tackles that did not result in injury.Tackling with incorrect head position relative to the ball carrier resulted in a significantly higher incidence of concussions, neck injuries, stingers and nasal fractures than tackling with correct head position. Tackles with shorter duration and distance before contact resulted in more injuries.
Abstract 24021: Sacubitril/Valsartan Attenuates Fibrosis and Improves Left Ventricular Function in a Rabbit Model of HFrEF
Authors: Juan Torrado, Chad Cain, Adolfo G Mauro, Ramzi A Ockaili, Francisco Romeo, John Nestler, Teja Devarakonda, Anindita Das, Fadi N Salloum
Journal: Circulation (2017)

Background: Sacubitril/Valsartan (SAC/VAL), a drug combining a neprilysin inhibitor and an angiotensin receptor blocker, was shown to reduce myocardial infarct size and left ventricular (LV) dysfunction in preclinical models of myocardial infarction (MI). In the PARADIGM-HF trial, SAC/VAL prevented the clinical progression of patients with heart failure (HF) more effectively than enalapril. Whether SAC/VAL attenuates cardiac fibrosis and improves LV function in a rabbit model of MI-induced HF with reduced ejection fraction (rEF) is unknown. Methods: Anesthetized adult male NZW rabbits (~2.5kg) underwent left thoracotomy and the left anterior descending (LAD) coronary artery was identified and occluded for 45 min followed by reperfusion. Weekly echocardiography was performed to confirm reduced EF (~40%), which was uniformly achieved at 5 weeks post MI. Subsequently, rabbits were randomized to orally receive placebo (volume-matched water, BID), SAC/VAL (10 mg/kg, BID) or VAL (9.1mg/kg/day) starting on week 6. At 10 weeks post MI, rabbits were sacrificed and hearts were harvested, fixed with 10% formalin and embedded in paraffin to assess myocardial fibrosis (Picrosirius red staining). Operators performing echocardiography, Picrosirius red staining and analysis were blinded to treatment allocation. Results: Two weeks after treatment initiation, a significant improvement in LVEF was observed in the SAC/VAL group compared to both placebo and VAL, a benefit that lasted throughout the entire study (Fig. A). The functional improvement observed was associated with a significant reduction in LV scar size compared to placebo at week 10 (Fig. B). However, when compared to VAL, the decrease in scar size did not reach statistical significance despite a clear trend. Conclusion: Our results suggest that SAC/VAL may offer superior benefits compared to equivalent dose of stand-alone VAL in attenuating LV scar size and improving LVEF in a rabbit model of ischemic HFrEF.
Sensitivity to the Deficits Associated With Traumatic Brain Injury or Chronic Traumatic Encephalopathy
Authors: Michael Hoffmann
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Surto de sarampo em adultos no noroeste da Grécia
Authors: G Mantzios, M Mastora, E Liapis, I Giannakakis, N K Akritidis
Journal: Eurosurveillance (1997)

A incidencia global do sarampo, na Grecia, diminuiu de forma notavel apos a introducao da vacinacao (ainda que nao haja disponiveis dados precisos), mas ainda ocorrem surtos esporadicos. Em 1965, a vacina monovalente antisarampo foi introduzida na Grecia e substituida em 1989 pela vacina tripla anti Sarampo, Parotidite, Rubeola (VASPR). A infeccao atinge quase sempre criancas mas tambem se encontram casos em adultos.
Demographics and disposition of patients in an academic outpatient palliative care practice.
Authors: Ali John Zarrabi, Karen Armstrong, Kimberly A. Curseen, Tammie E. Quest
Journal: Journal of Clinical Oncology (2017)

166 Background: Outpatient PC clinics strive to improve value by improving quality of care for patients while reducing cost. Justifying investment in outpatient PC necessitates characterizing the demographics and disposition of the patients whom these clinics serve. We sought to detail our outpatient palliative care practice in an urban academic medical center in the Southeast to serve a model for other institutions building a financial case for outpatient palliative medicine. Methods: A retrospective analysis from 2014-2017 was conducted on clinical and administrative data from the outpatient supportive oncology cohort at an urban Southern academic center. We performed multivariable logistic regression, t-tests, and chi square analyses to assess associations among variables of interest for patients. Results: Of our outpatient palliative care cohort of 3137 patients, 151 identify as white (51%) and 1377 as black (48%). Among whites 140 (9%) expired and 91% went to hospice compared to 151 (11%) nonwhites expired and 89% nonwhites went to hospice. Furthermore, 21% of non-whites were enrolled in commercial insurance while 79% were enrolled in government insurance compared to 28% whites in commercial insurance and 72% enrolled in government insurance. There were significant correlations among race, age, length of stay (LOS), and discharge disposition (p &lt; 0.05) and race and payer mix (X 2 = 17.67 df = 2 , p = .0001). White patients and older patients (P &lt; 0.05) were more likely to enter hospice care compared with minority patients (t = -.655, P &lt; 0.0001). Finally, 2942 patients (94%) received opioid pain medications, and over 90% had &gt; 5 readmissions. Conclusions: In our academic outpatient palliative care clinic we found most patients had governmental insurance, most were prescribed opiates, and older patients and white patients had significantly greater LOS and hospice enrollment compared to black patients. These data illustrate the diversity, payer mix, and disposition to expect when building a case to develop an outpatient palliative care practice in an academic urban medical center.
OC-066 Gut specific regulatory t cells – a new frontier for crohn’s disease therapy
Authors: R Goldberg, C Scotta, D Cooper, P Irving, J Sanderson, N Shpigel, F Marelli-Berg, G Lombardi, G Lord
Journal: Gut (2017)

Introduction  We have recently shown that Tregs isolated from the peripheral blood of patients with Crohn’s Disease (CD) can be expanded in vitro for therapeutic purposes. This is a critical step to developing cell based therapy for Crohn’s disease. The immune system used retinoic acid (ATRA) to induce a4b7 and thus prime Tregs to home to the gut. We sought use ATRA in-vitro in order to engineer gut specific Tregs for our Phase 1 trial in Crohn’s Disease. We then validated our findings in-vitro and in-vivo.  Method  Tregs were isolated from peripheral blood of CD patients. ATRA supplementation was tested in standard culture conditions. The expression of a4b7 was assessed by flow cytometry. Suppression assays were performed using autologous effector T cells (Teff). An ibidi flow chamber system coated with recombinant human MAdCAM-1 was used for in-vitro trafficking experiments. SCID mice xenografted with foetal intestinal small bowel were used for in-vivoexperiments.  Results  Ex-vivo expansion of Tregs in the presence of ATRA significantly induced the expression of a4b7 compared to Rapamycin alone (5.57%±3.12 vs 82.8%±9.5, p=0.0057) Cells treated with Rapa+ATRA maintained their superior suppressive ability compared to Rapamycin treated Tregs (95.8%±3.5% vs 91.15%±10.1% p=ns; at Treg:Teff 1:1 ratio). RAPA+ATRA Tregs did not produce IFNy or IL17 under pro-inflammatory cytokine challenge. When flowed through a MAdCAm-1 coated chamber, significantly higher numbers of Rapa+ATRA treated cells were observed to roll (Rapa 0.83±0.40 vs Rapa+ATRA 10.17±2.54 p=0.005), crawl (Rapa 0 vs Rapa+ATRA 4±0.89 p=0.001) and firmly adhere (Rapa 0.33±0.21 vs Rapa+ATRA 36.8±1.78, p  Conclusion  The addition of ATRA to Treg culture in-vitro confers a gut homing phenotype. This is functionally relevant in-vitro and in-vivo. The treatment maintains the highly suppressive and phenotypically stable phenotype of these cells. These gut specific Tregs will be implemented in our first in man trial Treg therapy for Crohn’s disease.  Disclosure of Interest  None Declared
Anal Cancer Risk Among People With HIV Infection in the United States
Authors: Vivian Colón-López, Meredith S. Shiels, Mark Machin, Ana P. Ortiz, Howard Strickler, Philip E. Castle, Ruth M. Pfeiffer, Eric A. Engels
Journal: Journal of Clinical Oncology (2017)

Purpose People with HIV infection have an elevated risk of anal cancer. However, recent calendar trends are incompletely described, and which population subgroups might benefit from cancer screening is unknown. Methods We used linked data from HIV and cancer registries in nine US areas (1996 to 2012). We calculated standardized incidence ratios to compare anal cancer incidence in people with HIV infection with the general population, used Poisson regression to evaluate anal cancer incidence among subgroups of people with HIV and to assess temporal trends, and estimated the cumulative incidence of anal cancer to measure absolute risk. Results Among 447,953 people with HIV infection, anal cancer incidence was much higher than in the general population (standardized incidence ratio, 19.1; 95% CI, 18.1 to 20.0). Anal cancer incidence was highest among men who have sex with men (MSM), increased with age, and was higher in people with AIDS than in those without AIDS (ie, HIV only; adjusted incidence rate ratio, 3.82; 95% CI, 3.27 to 4.46). Incidence among people with HIV increased steeply during 1996 to 2000 (annual percentage change, 32.8%; 95% CI, -1.0% to 78.2%), reached a plateau during 2001 to 2008, and declined during 2008 to 2012 (annual percentage change, -7.2%; 95% CI, -14.4% to 0.6%). Cumulative incidence after a 5-year period was high for MSM with HIV only age 45 to 59 or ≥ 60 years (0.32% to 0.33%) and MSM with AIDS age 30 to 44, 45 to 59, or ≥ 60 years (0.29% to 0.65%). Conclusion Anal cancer incidence is markedly elevated among people with HIV infection, especially in MSM, older individuals, and people with AIDS. Recent declines may reflect delayed benefits of HIV treatment. Groups with high cumulative incidence of anal cancer may benefit from screening.
New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital Imaging
Authors: Hailey E. Brighton, Steven P. Angus, Tao Bo, Jose Roques, Alicia C. Tagliatela, David B. Darr, Kubra Karagoz, Noah Sciaky, Michael L. Gatza, Norman E. Sharpless, Gary L. Johnson, James E. Bear
Journal: Cancer Research (2017)

Abstract Targeted therapeutics that are initially effective in cancer patients nearly invariably engender resistance at some stage, an inherent challenge in the use of any molecular-targeted drug in cancer settings. In this study, we evaluated resistance mechanisms arising in metastatic melanoma to MAPK pathway kinase inhibitors as a strategy to identify candidate strategies to limit risks of resistance. To investigate longitudinal responses, we developed an intravital serial imaging approach that can directly visualize drug response in an inducible RAF-driven, autochthonous murine model of melanoma incorporating a fluorescent reporter allele (tdTomatoLSL). Using this system, we visualized formation and progression of tumors in situ, starting from the single-cell level longitudinally over time. Reliable reporting of the status of primary murine tumors treated with the selective MEK1/2 inhibitor (MEKi) trametinib illustrated a time-course of initial drug response and persistence, followed by the development of drug resistance. We found that tumor cells adjacent to bundled collagen had a preferential persistence in response to MEKi. Unbiased transcriptional and kinome reprogramming analyses from selected treatment time points suggested increased c-Kit and PI3K/AKT pathway activation in resistant tumors, along with enhanced expression of epithelial genes and epithelial-mesenchymal transition downregulation signatures with development of MEKi resistance. Similar trends were observed following simultaneous treatment with BRAF and MEK inhibitors aligned to standard-of-care combination therapy, suggesting these reprogramming events were not specific to MEKi alone. Overall, our results illuminate the integration of tumor–stroma dynamics with tissue plasticity in melanoma progression and provide new insights into the basis for drug response, persistence, and resistance. Significance: A longitudinal study tracks the course of MEKi treatment in an autochthonous imageable murine model of melanoma from initial response to therapeutic resistance, offering new insights into the basis for drug response, persistence, and resistance. Cancer Res; 78(2); 542–57. ©2017 AACR.