tbuckley/cabot-search huggingface dataset:
Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
Authors: Francesco Sabbatino, Antonio Marra, Luigi Liguori, Giosuè Scognamiglio, Celeste Fusciello, Gerardo Botti, Soldano Ferrone, Stefano Pepe
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies in non-melanoma skin cancers, especially in basal cell carcinoma. The latter malignancy is often associated with both an impairment of the host immune response and a high mutation burden, suggesting that immune checkpoint inhibitor-based immunotherapy may be effective in the treatment of this tumor. <h3>Case presentation</h3> A 78-year-old woman was diagnosed with a metastatic non-small-cell-lung-cancer. Following the lack of response to two lines of systemic chemotherapy, she was treated with the anti-PD-1 monoclonal antibody nivolumab, obtaining a prolonged stable disease. Under nivolumab treatment, the patient developed a basal cell carcinoma of the nose. The latter was surgically resected. Immunohistochemical staining of tumor tissue showed a PD-L1 expression &lt; 1% and lack of human leukocyte antigen class I subunit (i.e. heavy and light chain) expression on tumor cells. In addition, a limited number of T cells (CD3+) was present in the tumor microenvironment, with a higher number of regulatory T cells (Foxp3+) and macrophages (Cd11b+) as compared to a low infiltration of activated cytotoxic T cells (CD8+/ Granzyme B+). Two months following the surgical removal of the tumor, while still on nivolumab treatment, the patient relapsed with a basal cell carcinoma in the same anatomic site of the previous surgical excision. The tumor displayed the same pathological characteristics. <h3>Conclusion</h3> Preclinical lines of evidence suggest a potential role of immune checkpoint inhibitors for basal cell carcinoma treatment. However, limited clinical data is available. In the patient we have described administration of the immune checkpoint inhibitor nivolumab for the treatment of a responsive non-small cell carcinoma was associated with the development and relapse of a basal cell carcinoma tumor. This association is likely to reflect the resistance of basal cell carcinoma cells to anti-PD-1 based immunotherapy because of a "cold" tumor microenvironment characterized by lack of human leukocyte antigen class I expression, low PD-L1 expression and high number of immune regulatory cells.
Updated Framework for Development of Evidence-Based Recommendations by the Advisory Committee on Immunization Practices
Authors: Grace Lee, Wendy Carr, Art Reingold, Paul Hunter, Grace Lee, Jon Temte, Doug Campos-Outcalt, Lorry Rubin, Sean O’Leary, Margot Savoy, Amir Qaseem, Nadine Sicard, Shainoor Ismail, Roshan Ramanathan, Rebecca Morgan, David Weber, Valéry Lavergne, Ned Calonge, Charles Wiysonge, Philippe DuClos, Melanie Marti, Thomas Harder, Gerhard Falkenhorst, Almea Matanock, Tamara Pilishvili, Kathleen Dooling, Carolyn Bridges, Megan Lindley, Tom Shimabukuro
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The Advisory Committee on Immunization Practices (ACIP)* is a federal advisory committee that provides expert advice to the Director of CDC and the Secretary of the U.S. Department of Health and Human Services in the form of recommendations on the use of vaccines and related agents for control of vaccine-preventable diseases in the U.S. civilian population (1,2). Work groups that gather, analyze, and prepare scientific information assist in the recommendation formulation process and present options for recommendations based on the scientific evidence they have assessed. Recommendations that are approved by a majority of ACIP's voting members are then reviewed by the Director of CDC and published in MMWR if approved by the director. This report briefly summarizes an update to the ACIP process for developing evidence-based recommendations that ACIP adopted at its February 2018 meeting.
Participant Protection in Phase 1 Pediatric Cancer Trials
Authors: Jonathan Kimmelman, Marcin Waligora, Holly Fernandez Lynch
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
Analysis of the first 2645 registrations at the research registry®: A global repository for all study types involving human participants
Authors: Alexander J Fowler, Naeem Dowlut, Richard Limb, Martinique Vella Baldacchino, Vinay Sonagara, Natalie George, Rachel Thavayogan, Buket Gundogan, Christopher Limb, Daniyal J Jafree, Riaz A Agha
Journal: International Journal of Surgery (2018)
Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers
Authors: Wouter Scheper, Sander Kelderman, Lorenzo F. Fanchi, Carsten Linnemann, Gavin Bendle, Marije A. J. de Rooij, Christian Hirt, Riccardo Mezzadra, Maarten Slagter, Krijn Dijkstra, Roelof J. C. Kluin, Petur Snaebjornsson, Katy Milne, Brad H. Nelson, Henry Zijlmans, Gemma Kenter, Emile E. Voest, John B. A. G. Haanen, Ton N. Schumacher
Journal: Nature Medicine (2018)
The bird’s-eye view on chromosome evolution
Authors: Guojie Zhang
Journal: Genome biology (2018)

The study of the evolution of chromosomal number and structure has long been of interest to evolutionary biologists. However, this research has been hindered by the lack of chromosome-level genome assemblies for multiple species across phylogenetic lineages. Three recent studies from same research group have demonstrated the power of bioinformatic approaches in producing chromosome level genome assemblies and reconstructing the karyotypic history of birds.
Ian Forgacs: flamboyant and modernising president of the British Society of Gastroenterology
Authors: Penny Warren
Journal: BMJ (2018)

Ian Forgacs

Credit: Helen Forgacs

Those at the 2016 awayday of the British Gastroenterology Society (BSG) did not expect Hamlet’s soliloquy to be on the agenda. But Ian Forgacs, the president, delighted in the unexpected. On the 400th anniversary of Shakespeare’s death, he performed the speech to a rapt audience. He was shrewd man with a disarming manner, and, as a colleague said, “He was born to be president. He handled it with aplomb.”

Forgacs worked to modernise the BSG and promote links worldwide, securing a memorandum of understanding with the Chinese Society of Gastroenterology. He was instrumental in delivering better training, including developing the specialty certificate examination, and he championed initiatives such as getting faster access to endoscopy.

Ian Christopher Forgacs was born on 13 October 1951 in Bromley, Kent. His mother, Eileen, was a nurse and his Hungarian father, Paul, a chest physician.

Forgacs and his younger brother, David, attended Sevenoaks School, where he …
How Community Health Workers Can Affect Health Care
Authors: Ryan Graddy, Michael Fingerhood
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Computed tomography abnormalities antedating mesothelioma diagnosis: a perspective on the natural history
Authors: Maged Hassan, Stamatoula Tsikrika, Rachelle Asciak, Rachel M. Mercer, Anwar El-Ganady, Najib M. Rahman
Journal: European Respiratory Journal (2018)

<b>Radiological evolution of MPM is difficult to infer. Previous pleural effusion or thickening warrants careful follow-up. Some patients don9t exhibit abnormalities a few months prior to diagnosis while others carry pleural abnormalities for several years.</b>http://ow.ly/uTGO30mJ8D2
Abstract 12684: Cardiorenal Outcomes and the Efficacy of Darbepoetin in Patients With Heart Failure, Reduced Ejection Fraction, Anemia and Advanced Chronic Kidney Disease
Authors: Akshay S Desai, Henry Krum, Changhong Yu, Scott M Wasserman, Eduard Apetrei, Vijay Chopra, Viacheslav Mareev, Aldo P Maggioni, John J McMurray, Marc A Pfeffer, Karl Swedberg, James B Young
Journal: Circulation (2014)

Background: Most trials in heart failure (HF) have excluded patients with advanced chronic kidney disease (CKD) and have not described renal as well as cardiovascular outcomes. We report cardiorenal outcomes in the RED-HF trial which randomized subjects with HF, EF≤40%, anemia, and creatinine ≤ 3 mg/dL to treatment with darbepoetin alfa (DA) or placebo. DA had no effect on mortality or the primary composite outcome of death from any cause or hospitalization for worsening heart failure. Methods: In RED-HF, we examined the association between CKD stage (defined by the KDOQI classification) and the primary composite outcome as well as the composite of death or end-stage renal disease (ESRD) in multivariable Cox models. Results: 379 of the 2278 enrolled subjects (16.7%) had Stage IV CKD (eGFR<30 mL/min/1.73m2). Stage IV CKD was associated with older age, female sex, white race, diabetes, hypertension, atrial fibrillation, loop diuretic use, more severe HF symptoms, lower hemoglobin, and lesser use of renin-an...
Abstract P226: HEalth Nutritional Index (HENI): A Health Burden Based Tool for Food and Diet Nutritional Evaluation
Authors: Katerina Stylianou, Victor L Fulgoni, Olivier Jolliet
Journal: Circulation (2018)

Introduction: The role of diets on human health is crucial and depends on the quality of the food we eat. A number of indexes help rank food items and evaluate diets based on their nutrient profiling and meeting dietary guidelines, respectively. Existing nutritional indexes fail to quantify the varying effects of major food groups and nutrients on human health. We introduce the HEalth Nutritional Index (HENI), a health burden-based scoring system in disability adjusted life years (DALYs) that uses epidemiological evidence from the Global Burden of Disease (GBD) to rank and evaluate food items and diets. Methods: HENI accounts for the health effects of 8 major food groups (nuts and seeds, whole grains, fruits, vegetables, milk, sugar-sweetened beverages, red meat, and processed meat) and 6 nutrients (omega-3, calcium, fiber, polyunsaturated fatty acids, trans fat, and sodium), identified by the GBD as dietary risk factors. The HENI factors are estimated by coupling age- and gender-adjusted outcome-specific incidence rates with risk ratios (RR) and severity factors, measuring positive or detrimental effects in avoided μDALY/g. We determine the food group and nutrient profile for each of the 5000+ consumed food items in the What We Eat in America 2009-2014 dataset, using multiple databases such as the Food Patterns Equivalents Database (FPED), the Food and Nutrient Database for Dietary Studies (FNDDS), and the USDA National Nutrient Database for Standard Reference (SR). We then derive the HENI scores for 100 kcal, 100 grams or 1 serving of each food item by multiplying the food group and nutrient composition by their respective HENI factors. Results: HENI factors for food group and nutrient range between -8 μDALY/g for sodium, up to 57 μDALY/g for omega-3 from fish and seafood. HENI score typically ranges from -30 avoided μDALY/100kcal for e.g. soft drinks, up to +50 avoided μDALY/100kcal, for beneficial food items such as fish, fruits, vegetables, and nuts. The majority of the health effect is associated with cardiovascular diseases, with some food items affecting certain cancers (e.g. health benefit for colorectal cancer with milk). Absolute HENI scores and ranking of food items vary substantially when using 100 kcal, 100 grams or 1 serving as a basis for comparison. In a sensitivity study, we consider the indirect effect of saturated fat via total blood cholesterol is considered which can play an important role for animal-based food items, requiring further investigation. The HENI factors are applicable under the assumption that the overall dietary intake of each GBD food group and nutrient is within the effective intake range, below the theoretical risk level limit. Conclusion: The proposed HENI index enables to quantify the human health impact of thousands of food items, bringing on the same scale different nutritional impacts, allowing for a comprehensive assessment of food items and diets.
Massive release of the histamine-degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients
Authors: Thomas Boehm, Birgit Reiter, Robin Ristl, Karin Petroczi, Wolfgang Sperr, Thomas Stimpfl, Peter Valent, Bernd Jilma
Journal: Allergy (2018)

Abstract Background Histaminolytic activity mediated by diamine oxidase (DAO) is present in plasma after induction of severe anaphylaxis in rats, guinea pigs, and rabbits. Heparin released during mast cell degranulation in the gastrointestinal tract might liberate DAO from heparin‐sensitive storage sites. DAO release during anaphylaxis has not been demonstrated in humans. Methods Plasma DAO, tryptase, and histamine concentrations of four severe anaphylaxis events were determined at multiple serial time points in two patients with systemic mastocytosis. The histamine degradation rates were measured in anaphylaxis samples and in pregnancy sera and plasma with comparable DAO concentrations. Results Mean DAO (132 ng/mL) and tryptase (304 ng/mL) concentrations increased 187‐ and 4.0‐fold, respectively, over baseline values (DAO 0.7 ng/mL, tryptase 76 ng/mL) during severe anaphylaxis. Under non‐anaphylaxis conditions, DAO concentrations were not elevated in 29 mastocytosis patients compared to healthy volunteers and there was no correlation between DAO and tryptase levels in mastocytosis patients. The histamine degradation rate of DAO in plasma from mastocytosis patients during anaphylaxis is severely compromised compared to DAO from pregnancy samples. Conclusion During severe anaphylaxis in mastocytosis patients, DAO is likely released from heparin‐sensitive gastrointestinal storage sites. The measured concentrations can degrade histamine, but DAO activity is compromised compared to pregnancy samples. For accurate histamine measurements during anaphylaxis, DAO inhibition is essential to inhibit further histamine degradation after blood withdrawal. Determination of DAO antigen levels might be of clinical value to improve the diagnosis of mast cell activation.
Introduction of novel agents in the treatment of primary CNS lymphoma
Authors: Christian Grommes, Lakshmi Nayak, Han W Tun, Tracy T Batchelor
Journal: Neuro-Oncology (2018)

Novel insights into the pathophysiology of primary central nervous system lymphoma (PCNSL) have identified the B-cell receptor and Toll-like receptor pathway as well as immune evasion and suppressed tumor immune microenvironment as a key mechanism in the pathogenesis of PCNSL. Small molecules and novel agents targeting these aberrant pathways have been introduced into clinical trials targeting the recurrent or refractory PCNSL patient population. Agents like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting. Here, we give an overview about the recent, exciting developments in PCNSL and summarize the results of clinical trials using novel agents in the recurrent and refractory salvage setting, which include immune checkpoint inhibitors, IMiDs, as well as BTK, phosphatidylinositol-3 kinase, and mammalian target of rapamycin inhibitors.
Comprehensive approach to diagnosis and treatment of newly diagnosed primary CNS lymphoma
Authors: Christian Grommes, James L Rubenstein, Lisa M DeAngelis, Andres J M Ferreri, Tracy T Batchelor
Journal: Neuro-Oncology (2018)

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the brain parenchyma, spinal cord, eyes, and cerebrospinal fluid without evidence of systemic, non-CNS involvement. PCNSL is uncommon and only a few randomized trials have been completed in the first-line setting. Over the past decades, the prognosis of PCNSL has improved, mainly due to the introduction and widespread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Despite this progress, durable remission is recorded in only 50% of patients, and therapy can be associated with significant late neurotoxicity. Here, we overview the epidemiology, clinical presentation, staging evaluation, prognosis, and current up-to-date treatment of immunocompetent PCNSL patients.
Abstract 14850: Independent Role of the Priming and Triggering of the NLRP3 Inflammasome in the Heart
Authors: Stefano Toldo, Eleonora Mezzaroma, Matthew D McGeough, Carla A Pena, Carlo Marchetti, Chiara Sonnino, Benjamin W Van Tassell, Adolfo G Mauro, Fadi N Salloum, Hal M Hoffman, Antonio Abbate
Journal: Circulation (2014)

Introduction: The NLRP3 inflammasome is activated in the heart following ischemic injury, and it promotes cardiac dysfunction. Ischemic injury establishes both a priming signal (leading to transcription of inflammasome components) and a trigger (NLRP3 activation). Whether activation of NLRP3 (in absence of priming) represents the limiting step in the formation of the inflammasome in the heart is unknown. Hypothesis: Both priming and the triggering signals in the heart are necessary for the formation of the inflammasome and ensuing cardiac dysfunction. Methods: We induced systemic expression of a floxed mutant NLRP3-A350V, that is constitutively active, in 10 mice using a tamoxifen-inducible Cre recombinase, to create a condition in which NLRP3 is activated, in absence or presence of priming with low dose LPS (2 mg/kg). Molecular analyses were performed on the heart and the spleen (myeloid organ not dependent on priming) to measure caspase-1 activity using a fluorogenic assay, mRNA expression of the component of the inflammasome (caspase-1 and IL-1β), and echocardiography to measure left ventricular (LV) dimension and systolic function. Results: NLRP3-A350V mutant mice had increased caspase-1 activity in the spleen but not in the heart and had normal LV systolic function (Figure), showing that in NLRP3 activation without priming is insufficient to induce inflammasome formation in the heart nor LV systolic dysfunction. Priming with LPS induced the expression of the inflammasome components in the heart which in absence of NLRP3 activation (control mouse) had no effects on LV systolic function, whereas in the presence of NLRP3 activation (mutant mouse) led to reduced LV systolic function and premature death (Figure). Conclusions: The inflammasome formation in the heart requires a priming signal to be coupled with activation of NLRP3 in order to induce LV dysfunction.
Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study
Authors: Olivier Rouvière, Philippe Puech, Raphaële Renard-Penna, Michel Claudon, Catherine Roy, Florence Mège-Lechevallier, Myriam Decaussin-Petrucci, Marine Dubreuil-Chambardel, Laurent Magaud, Laurent Remontet, Alain Ruffion, Marc Colombel, Sébastien Crouzet, Anne-Marie Schott, Laurent Lemaitre, Muriel Rabilloud, Nicolas Grenier, Nicolas Barry Delongchamps, Romain Boutier, Flavie Bratan, Serge Brunelle, Philippe Camparo, Pierre Colin, Jean-Michel Corréas, François Cornélis, François Cornud, Fanny Cros, Jean-Luc Descotes, Pascal Eschwege, Gaelle Fiard, Jean-Philippe Fendler, Hocine Habchi, Philippe Hallouin, Ahmed Khairoune, Hervé Lang, Yann Lebras, Frédéric Lefèvre, Bernard Malavaud, Paul Cezar Moldovan, Nicolas Mottet, Pierre Mozer, Pierre Nevoux, Gaele Pagnoux, Gilles Pasticier, Daniel Portalez, Eric Potiron, Athivada Soto Thammavong, Marc-Olivier Timsit, Arnault Viller, Jochen Walz
Journal: The Lancet Oncology (2018)