tbuckley/cabot-search huggingface dataset:
Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies
Authors: Alberto Puccini, Francesca Battaglin, Maria Laura Iaia, Heinz-Josef Lenz, Mohamed E Salem
Journal: Journal for ImmunoTherapy of Cancer (2020)

In the last few years, the unprecedented results of immune checkpoint inhibitors have led to a paradigm shift in clinical practice for the treatment of several cancer types. However, the vast majority of patients with gastrointestinal cancer do not benefit from immunotherapy. To date, microsatellite instability high and DNA mismatch repair deficiency are the only robust predictive biomarkers of response to immune checkpoint inhibitors. Unfortunately, these patients comprise only 5%-10% of all gastrointestinal cancers. Several mechanisms of both innate and adaptive resistance to immunotherapy have been recognized that may be at least in part responsible for the failure of immune checkpoint inhibitors in this population of patients. In the first part of this review article, we provide an overview of the main clinical trials with immune checkpoint inhibitors in patients with gastrointestinal cancer and the role of predictive biomarkers. In the second part, we discuss the actual body of knowledge in terms of mechanisms of resistance to immunotherapy and the most promising approach that are currently under investigation in order to expand the population of patients with gastrointestinal cancer who could benefit from immune checkpoint inhibitors.
Development of a new method to calculate individuals’ melanoma risk
Authors: K. Vuong, B.K. Armstrong, M. Drummond, J.L. Hopper, J.H. Barrett, J.R. Davies, D.T. Bishop, J. Newton‐Bishop, J.F. Aitken, G.G. Giles, H. Schmid, M.A. Jenkins, G.J. Mann, K. McGeechan, A.E. Cust
Journal: British Journal of Dermatology (2020)

Melanoma is a cancer that develops in the melanocytes, the pigment cells of the skin. Melanoma incidence rates, which show how common it is, have been increasing in people with fair skin, with the highest rates in Australia, New Zealand, North America and Europe. In Australia, one in 14 men and one in 24 women will be diagnosed with melanoma during their lifetime. Risk factors for melanoma include sun exposure, sunbed use, the number of moles on the skin, the skin's sensitivity to the sun, the number of freckles, skin colour, eye colour, hair colour, family history and a number of susceptibility genes (genes that place you at higher risk). Melanoma risk prediction models, which combine many individual melanoma risk factors into an overall risk, may be useful in the prevention of melanoma by matching prevention strategies (interventions) to the patient's melanoma risk levels. Many melanoma risk prediction models use self‐assessed risk factors because it is quicker and less costly compared to the clinical (medical) assessment of risk factors, but many people underestimate the number of moles they have. This study aims to derive a melanoma risk prediction model, which includes the number of moles on the body and solar lentigines (darker skin patches caused by the sun) as clinically‐assessed risk factors, and pigmentation (skin colour) characteristics, sun exposure, family history and history of skin cancer as self‐assessed risk factors. The number of moles is the strongest risk factor in the model. The model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma. In a clinical setting, this model may help clinicians identify patients for targeted prevention strategies based on the patient's melanoma risk. This is a summary of the study: Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines
THU0224 Anti-TNF-α Therapy Reduces Endothelial Cell Activation in Non-Diabetic Ankylosing Spondylitis Patients
Authors: R. Lόpez-Mejías, F. Genre, J.A. Miranda-Filloy, B. Ubilla, V. Mijares, B. Carnero-Lόpez, I. Gόmez-Acebo, T. Dierssen-Sotos, S. Remuzgo-Martínez, R. Blanco, T. Pina, C. González-Juanatey, J. Llorca, M.Ά. González-Gay
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Endothelial dysfunction can be detected by the presence of elevated levels of biomarkers of endothelial cell activation. In this study we aimed to establish whether correlations of these biomarkers with characteristics of patients with ankylosing spondylitis (AS) exist. We also studied the effect of anti-TNF-α therapy on these biomarkers. <h3>Methods</h3> Serum sE-selectin, MCP-1 and sVCAM-1 levels were measured by ELISA in 30 non-diabetic AS patients undergoing anti-TNF-α therapy, immediately before and after an infusion of infliximab. Correlations of these biomarkers with clinical features, systemic inflammation, metabolic syndrome, and other serum and plasma biomarkers of cardiovascular risk were studied. Potential changes in the concentration of these biomarkers following an infliximab infusion were also assessed. <h3>Results</h3> sE-selectin showed a positive correlation with CRP (p=0.02) and with other endothelial cell activation biomarkers such as sVCAM-1 (p=0.019) and apelin (p=0.008). sVCAM-1 negatively correlated with BMI (p=0.018), diastolic blood pressure (p=0.008) and serum glucose (p=0.04). sVCAM-1 also showed a positive correlation with VAS spinal pain (p=0.014) and apelin (p&lt;0.001). MCP-1 had a negative correlation with LDL-cholesterol (p=0.026) and ESR (p=0.017). Patients with hip involvement and synovitis and/or enthesitis in other peripheral joints showed higher levels of MCP-1 (p=0.004 and 0.02, respectively). A single infliximab infusion led to a significant reduction in sE-selectin (p=0.0015) and sVCAM-1 (p=0.04). <h3>Conclusions</h3> Endothelial dysfunction correlates with inflammation and metabolic syndrome features in patients with AS. A beneficial effect of the anti-TNF-α blockade on endothelial dysfunction, manifested by a reduction of levels of biomarkers of endothelial cell activation, was observed. <h3>Acknowledgements</h3> This study was supported by European Union FEDER funds and "Fondo de Investigaciόn Sanitaria" (Grants PI06/0024, PS09/00748, and PI12/00060) (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013, from "Instituto de Salud Carlos III" (ISCIII) (Spain). FG and BU are supported by funds from the RETICS Program (RIER). RLM is a recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (Spain). <h3>Disclosure of Interest</h3> None declared
Abstract 14819: Multimodality Image Approach to Evaluate the Delivery and Impact of a Novel Imageable Hydrogel Post Myocardial Infarction
Authors: Ricardo Avendano, Dan Midgett, Shin Rong Lee, Stephanie Thorn, Christi Hawley, Marina Mamarian, Selen Uman, Jay D Humphrey, James Duncan, Jason A Burdick, Albert J Sinusas
Journal: Circulation (2019)

Introduction: Myocardial Infarction (MI) is often complicated by post-MI left ventricular (LV) remodeling and heart failure. Recent efforts have been directed at the intramyocardial delivery of the...
An elastic gel consisting of natural polyphenol and pluronic for simultaneous dura sealing and treatment of spinal cord injury
Authors: Yu Wang, Changnan Xie, Peng Wang, Xinyu Wang, Changping Wang, Xiaojie Xun, Chaowei Lin, Zhihui Huang, Yiyun Cheng, Lei Li, Honglin Teng
Journal: Journal of Controlled Release (2020)
Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition
Authors: Martin Beaumont, Charlotte Paës, Eloïse Mussard, Christelle Knudsen, Laurent Cauquil, Patrick Aymard, Céline Barilly, Béatrice Gabinaud, Olivier Zemb, Sandra Fourre, Roselyne Gautier, Corinne Lencina, Hélène Eutamène, Vassilia Theodorou, Cécile Canlet, Sylvie Combes
Journal: Gut Microbes (2020)

In suckling mammals, the onset of solid food ingestion is coincident with the maturation of the gut barrier. This ontogenic process is driven by the colonization of the intestine by the microbiota. However, the mechanisms underlying the microbial regulation of the intestinal development in early life are not fully understood. Here, we studied the co-maturation of the microbiota (composition and metabolic activity) and of the gut barrier at the suckling-to-weaning transition by using a combination of experiments in vivo (suckling rabbit model), ex vivo (Ussing chambers) and in vitro (epithelial cell lines and organoids). The microbiota composition, its metabolic activity, para-cellular epithelial permeability and the gene expression of key components of the gut barrier shifted sharply at the onset of solid food ingestion in vivo, despite milk was still predominant in the diet at that time. We found that cecal content sterile supernatant (i.e. containing a mixture of metabolites) obtained after the onset of solid food ingestion accelerated the formation of the epithelial barrier in Caco-2 cells in vitro and our results suggested that these effects were driven by the bacterial metabolite butyrate. Moreover, the treatment of organoids with cecal content sterile supernatant partially replicated in vitro the effects of solid food ingestion on the epithelial barrier in vivo. Altogether, our results show that the metabolites produced by the microbiota at the onset of solid food ingestion contribute to the maturation of the gut barrier at the suckling-to-weaning transition. Targeting the gut microbiota metabolic activity during this key developmental window might therefore be a promising strategy to promote intestinal homeostasis.
Recurrent miscarriage
Authors: M Tasker, C Verduijn, T Anwar, A.J Dow, K Zaw, C.M Joshi, L Hanna, P Doody, H.J.A Carp, I Ben-Shlomo, S Mashiach, GordonH Ramsden, PaulR Manasse, PeterM Johnson, AdamH Balen, Lesley Regan, ElizabethJ Owen, HowardS Jacobs
Journal: The Lancet (1990)
Addressing Social Determinants of Health in the Care of Patients With Heart Failure: A Scientific Statement From the American Heart Association
Authors: Connie White-Williams, Laura P. Rossi, Vera A. Bittner, Andrea Driscoll, Raegan W. Durant, Bradi B. Granger, Lucinda J. Graven, Lisa Kitko, Kim Newlin, Maria Shirey
Journal: Circulation (2020)

Heart failure is a clinical syndrome that affects >6.5 million Americans, with an estimated 550 000 new cases diagnosed each year. The complexity of heart failure management is compounded by the number of patients who experience adverse downstream effects of the social determinants of health (SDOH). These patients are less able to access care and more likely to experience poor heart failure outcomes over time. Many patients face additional challenges associated with the cost of complex, chronic illness management and must make difficult decisions about their own health, particularly when the costs of medications and healthcare appointments are at odds with basic food and housing needs. This scientific statement summarizes the SDOH and the current state of knowledge important to understanding their impact on patients with heart failure. Specifically, this document includes a definition of SDOH, provider competencies, and SDOH assessment tools and addresses the following questions: (1) What models or frameworks guide healthcare providers to address SDOH? (2) What are the SDOH affecting the delivery of care and the interventions addressing them that affect the care and outcomes of patients with heart failure? (3) What are the opportunities for healthcare providers to address the SDOH affecting the care of patients with heart failure? We also include a case study (Data Supplement) that highlights an interprofessional team effort to address and mitigate the effects of SDOH in an underserved patient with heart failure.
Urinary Tract Infections in Older Men
Authors: Manuel Etienne, Tatiana Galperine, François Caron
Journal: New England Journal of Medicine (2016)

Key Clinical PointsUrinary Tract Infections in Older Men The prevalence of bacteriuria and the incidence of urinary tract infection are substantially higher among older men than among younger men. The majority of older men with urinary tract infection have underlying urologic abnormalities. Effective treatment of infection requires determining whether the site of infection is the kidney, bladder, or prostate. Effective management of symptomatic episodes requires selection of antimicrobial therapy on the basis of urine culture. Chronic bacterial prostatitis requires prolonged antimicrobial therapy (30 days). Men with recurrent episodes who do not have urologic abnormalities that can be corrected or identified may require long-term suppressive therapy with antimicrobial agents.
Targeting T-Cell Receptor β-Constant Domain for Immunotherapy of T-Cell Malignancies
Authors: Paul Michael Maciocia, Patrycja Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U. Akarca, Shimobi Onuoha, David Cole, Andrew Sewell, Karl S Peggs, David C. Linch, Teresa Marafioti, Martin A Pule
Journal: Blood (2016)
THE TREATMENT OF MULTIPLE SCLEROSIS
Journal: JAMA (1922)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical Prostatectomy
Authors: Stephen J. Freedland, Elizabeth B. Humphreys, Leslie A. Mangold, Mario Eisenberger, Frederick J. Dorey, Patrick C. Walsh, Alan W. Partin
Journal: JAMA (2005)

The natural history of biochemical recurrence after radical prostatectomy can be long but variable. Better risk assessment models are needed to identify men who are at high risk for prostate cancer death early and who may benefit from aggressive salvage treatment and to identify men who are at low risk for prostate cancer death and can be safely observed.To define risk factors for prostate cancer death following radical prostatectomy and to develop tables to risk stratify for prostate cancer-specific survival.Retrospective cohort study of 379 men who had undergone radical prostatectomy at an urban tertiary care hospital between 1982 and 2000 and who had a biochemical recurrence and after biochemical failure had at least 2 prostate-specific antigen (PSA) values at least 3 months apart in order to calculate PSA doubling time (PSADT). The mean (SD) follow-up after surgery was 10.3 (4.7) years and median follow-up was 10 years (range, 1-20 years).Prostate cancer-specific mortality.Median survival had not been reached after 16 years of follow-up after biochemical recurrence. Prostate-specific doubling time (<3.0 vs 3.0-8.9 vs 9.0-14.9 vs > or =15.0 months), pathological Gleason score (< or =7 vs 8-10), and time from surgery to biochemical recurrence (< or =3 vs >3 years) were all significant risk factors for time to prostate-specific mortality. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer-specific survival at year 15 after biochemical recurrence.Clinical parameters (PSADT, pathological Gleason score, and time from surgery to biochemical recurrence) can help risk stratify patients for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. These preliminary findings may serve as useful guides to patients and their physicians to identify patients at high risk for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy to enroll them in early aggressive treatment trials. In addition, these preliminary findings highlight that survival in low-risk patients can be quite prolonged.
Targeting aberrant DNA hypermethylation as a driver of ATL leukemogenesis by using the new oral demethylating agent OR-2100
Authors: Tatsuro Watanabe, Satoshi Yamashita, Hiroshi Ureshino, Kazuharu Kamachi, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Nao Yoshida, Naoko Hattori, Hideaki Nakamura, Akemi Sato, Atsushi Kawaguchi, Naoko Sueoka-Aragane, Kensuke Kojima, Seiji Okada, Toshikazu Ushijima, Shinya Kimura, Eisaburo Sueoka
Journal: Blood (2020)
Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline
Authors: James D. Chalmers, Irena F. Laska, Frits M.E. Franssen, Wim Janssens, Ian Pavord, David Rigau, Melissa J. McDonnell, Nicolas Roche, Don D. Sin, Daiana Stolz, Samy Suissa, Jadwiga Wedzicha, Marc Miravitlles
Journal: European Respiratory Journal (2020)

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD. Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology. After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL −1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn. A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.
Two cases of food-borne botulism in Finland caused by conserved olives, October 2011
Authors: K Jalava, K Selby, A Pihlajasaari, E Kolho, E Dahlsten, N Forss, T Bäcklund, H Korkeala, T Honkanen-Buzalski, T Hulkko, Y Derman, A Järvinen, H Kotilainen, L Kultanen, P Ruutu, O Lyytikaïnen, M Lindström
Journal: Eurosurveillance (2011)

In October 2011 in Finland, two persons fell ill with symptoms compatible with botulism after having eaten conserved olives stuffed with almonds. One of these two died. Clostridium botulinum type B and its neurotoxin were detected in the implicated olives by PCR and mouse bioassay, respectively. The olives were traced back to an Italian manufacturer and withdrawn from the market. The public and other European countries were informed through media and Europe-wide notifications.
Comparison of 68Ga-FAPI and 18F-FDG PET/CT in a Patient With Cholangiocellular Carcinoma
Authors: Yizhen Pang, Bing Hao, Qihang Shang, Long Sun, Haojun Chen
Journal: Clinical Nuclear Medicine (2020)

Abstract The present study compared 68 Ga-FAPI and 18 F-FDG PET/CT in a patient with cholangiocellular carcinoma. In this case, 68 Ga-FAPI PET shows much higher tumor-to-background contrast of primary tumor and reveals more metastatic lesions, especially the micrometastases of bones, than 18 F-FDG PET.
Radiomics as Applied in Precision Medicine
Authors: Faiq Shaikh, Benjamin Franc, Francisca Mulero
Journal: Clinical Nuclear Medicine (2020)

Radiomics can be defined as the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput from medical images obtained with various modalities, including nuclear medicine modalities of Single photon emission computed tomography (SPECT) and Positron emission tomography (PET). We describe it as the process of transferring the medical imaging interpretation knowledge and skill set from humans to machines in a way that they can see more, process more information, and have deeper insights into what the disease is and how it behaves and might respond to therapeutic intervention. Radiomics methods can be applied across various cancers to identify tumor phenotype characteristics in the images that correlate with their likelihood of survival, as well as their association with the underlying driving biology. Identifying this characteristic set of features called tumor signature holds tremendous value in predicting cancer behavior and progression, which in turn has the potential to predict cancer's response to various therapeutic options (Fig. 3.1). Moreover, we are beginning to see the application of radiomics principles in non-oncologic indications as well, such as cardiovascular disease. In allowing us to have this capacity, radiomics holds the promise of driving the engine of precision medicine. However, there are numerous challenges in the validation methods needed to establish radiomics as a clinically viable solution.
CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma
Authors: Quan Zhou, Yangyang Qi, Zewei Wang, Han Zeng, Hongyu Zhang, Zhaopei Liu, Qiuren Huang, Ying Xiong, Jiajun Wang, Yuan Chang, Qi Bai, Yu Xia, Yiwei Wang, Li Liu, Le Xu, Bo Dai, Jianming Guo, Yu Zhu, Weijuan Zhang, Jiejie Xu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Patients with BRCA1-associated protein 1 (BAP1)-mutant clear cell renal cell carcinoma (ccRCC) have worse prognosis. C-C chemokine receptor 5 (CCR5) plays an important role in ccRCC development and its expression is elevated in BAP1-mutant tumors.533 patients with ccRCC from The Cancer Genome Atlas cohort and 797 patients with ccRCC from the Shanghai cohort were enrolled. In vitro and in vivo studies were conducted with human ccRCC tumors and murine tumor models. The association between BAP1 and CCR5 or its ligands was assessed by immunohistochemistry, flow cytometry, real-time PCR and ELISA. Survival was compared between different subpopulations of patients using Kaplan-Meier curve. Therapeutic effect of CCR5 blockade was validated using human ccRCC tumors and murine models.Expression of CCR5 and its ligands were elevated in BAP1-mutant patients with ccRCC. High CCR5 expression was indicative of poor prognosis in BAP1-low group of patients. CCR5 blockade prolonged the survival of tumor-bearing mice, resulting in enhanced cytotoxicity of T cells and antigen presentation of dendritic cells but repressed immune checkpoint expression. CCR5 ligands could recruit CCR5+ regulatory T cells to the tumor microenvironment. Additionally, BAP1-mutant ccRCC tumor cells secreted CCR5 ligands, which increased programmed cell death ligand 1 expression. However, both processes could be inhibited by CCR5 blockade. Study limitations include the unclear impact of CCR5 expressed by other cell populations.CCR5 in BAP1-mutant ccRCC results in an immune-suppressive microenvironment. Targeting CCR5 could provide a potential therapeutic benefit for patients.NCT01358721, CA209-009.