tbuckley/cabot-search huggingface dataset:
Palliative medicine
Authors: M. Lloyd-Williams
Journal: BMJ (1999)

Although a young specialty, palliative medicine is now the 11th largest and one of the fastest growing, but still many people shrug their shoulders when asked what we do. After three and half years in post, I still get letters from the university addressed to me at the “Department of Palaeontology Medicine.” The word palliative is derived from the Latin “pallium,” which means to cloak or hide. Palliative medicine is the specialist care of patients who have a life threatening, incurable illness, with the aim of treating their symptoms so that they can live their remaining life as comfortably as possible. Despite many changes in medical education we still do not train new generations of doctors to deal with the reality of progressive chronic illness.

Palliative medicine encompasses a wide range of skills, both intellectual and people centred - the palliation of physical symptoms is a large part of the work, but the holistic care of patients includes their psychological, social, and spiritual wellbeing. This care often extends after the death of a patient to the bereaved relatives and friends. It provides an opportunity to work with medical colleagues in all specialties and with general practitioners and a wide range of paramedical staff. These close working relationships are often fostered by the shared care of individual patients and by the sharing of knowledge and skills. Some of the most challenging aspects of the work involve supporting patients and families in ethical decision making, often in highly charged emotional situations, and there is a need for considerable diplomacy.

Historically, specialists in palliative medicine largely worked in hospices - independent units often funded by the local community - but consultants now have an increasing role in hospital symptom control teams and …
Latent Rheumatic Heart Disease
Authors: Andrea Beaton, Twalib Aliku, Alyssa Dewyer, Marni Jacobs, Jiji Jiang, Chris T. Longenecker, Sulaiman Lubega, Robert McCarter, Mariana Mirabel, Grace Mirembe, Judith Namuyonga, Emmy Okello, Amy Scheel, Emmanuel Tenywa, Craig Sable, Peter Lwabi
Journal: Circulation (2017)

Background: Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes. Methods: This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect. Results: Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (interquartile range, 2.0–2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic improvement, respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome. Conclusions: Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.
Fifty‐two words for snow: dermatologists naming epidermal naevi
Authors: S. Asch, J.L. Sugarman
Journal: British Journal of Dermatology (2017)

In the April 2017 issue of BJD, Kuentz et al (1) report an FGFR2 mutation in a subtype of nevus sebaceus (NS). On review of the histopathology, we question the clinical diagnosis and feel that these cases may better fit with keratinocytic epidermal nevus (KEN) or remain unclassified “epidermal nevi”. Both KEN and NS are papillomatous with epidermal hyperplasia (2), and while the authors note “small foci of sebaceous glands and immature hair follicle buds”, they wisely observe that the early gestational age may have limited the full adnexal development and thus, it is possible these may have developed into other clinical subtypes of epidermal nevi.

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Mechanisms of gut microbiota-mediated bone remodeling
Authors: Jing Yan, Ayumi Takakura, Kambiz Zandi-Nejad, Julia F. Charles
Journal: Gut Microbes (2017)

The mechanisms underlying the systemic effects mediated by gut microbiota are under active investigation. In addition to local, direct effects of gut microbiota on the host, metabolic products from microbiota may act peripherally, reaching distal organs through the circulation. In our recent publication we demonstrated that gut microbiota influence bone remodeling distally, promoting both bone resorption and formation. We proposed that these effects are mediated, at least in part, by the induction of insulin like growth factor (IGF-1) by the microbiota metabolite short chain fatty acids (SCFA). Here we explore additional mechanisms by which microbial metabolites could directly or indirectly alter host bone remodeling. We discuss whether SCFA directly modulate bone resorption by their actions on osteoclasts, and test the possibility that serotonin is another gut microbiota derived long-distance mediator of effects on bone remodeling. A detailed understanding of the mechanisms of microbiota effect on bone remodeling could help establish potential therapeutic strategies to promote bone health.
Abstract 20701: Favorable and Unfavorable Vascular Responses Early After Second-Generation Drug Eluting Stent Implantation: An Optical Coherence Tomographic Study
Authors: Yuta Oishi, Shigeyuki Watanabe, Masahiro Toyama, Eiji Ojima, Yumiko Muta, Shunsuke Maruta, Yasuhisa Kuroda
Journal: Circulation (2016)

Introduction: Early phase vascular response to various types of second-generation drug eluting stents(DES) is not well known. Hypothesis: Early phase vascular response to second-generation stent va...
Use of electrospun collagen scaffolds as 3-D cellular models for testing anti-neoplastic agents
Authors: Chu Zhang, Olga Hartman, Kristin Sisson, John Rabolt, Nicholas Petrelli, Mary Farach-Carson
Journal: Cancer Research (2008)

5127   Epithelial tumors form from cells that are released from their natural basement membrane and form 3-D structures that interact with each other and with the microenvironment of the tissue around the tumor, often collagen. Cancer cells growing as monolayers on tissue culture plastic do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as perfect models for testing of pharmacologically active compounds, including those that are being tested as anti-neoplastics). This work seeks to create new 3-D cellular materials possessing properties more similar to those in native tissues surrounding cancers, specifically electrospun micro- and nanofibrous scaffolds that support tumor growth in 3-D. Electrospinning creates spider web type fibers on which cells are grown for characterization and testing of anti-cancer compounds. The fibers produced during the electrospinning process are nanoscale, with diameters ranging from 40 to 2000 nm compared to traditional textile fibers that have diameters of 5-200 μm. The primary advantage of electrospinning is that it uses tiny quantities (50-100mg-the quantity that might result from a custom synthesis) of polymer in solution to form micro- and nanofibers. A second advantage is that additional components, e.g., small molecules, a second polymer, or cell binding factors can be added to the polymer solution and often can be incorporated into the fiber during the electrospinning process. We have optimized conditions to grow cancer cells (prostate cancer bone metastatic line C4-2B and osteosarcoma line MG-63) on these matrices for use in cancer killing studies. Data indicate that while cells attach to plates coated with collagen approximately 4X more efficiently than they initially do to electrospun membranes, by day 5 there are 4-5X more cells growing on the scaffolds. MG-63 and C4-2B cells both migrate through the depth of the electrospun membrane and by day 5 confocal images show cell processes extending throughout the membrane. C4-2B cells begin to form small colonies resembling tumors by day 5. Cells on electrospun collagen are more resistant to killing by all agents tested to date including camptothecin, rapamycin, and docetaxel than are their counterparts on collagen coated plastic. We conclude that 3-D electrospun membranes are amenable to high throughput drug screening for cancer cell susceptibility and combination killing.
Sudden onset headache in a 50 year old woman
Authors: Divyansh Gulati, Michael William Shea, James Ray
Journal: BMJ (2017)

A 50 year old woman presented to the emergency department several hours after the sudden onset of a severe headache with associated neck stiffness, photophobia, and vomiting. She reported having a dental abscess, and was taking norethisterone regularly for persistent vaginal bleeding. She had a 50 pack year smoking history. She was afebrile, alert (Glasgow coma scale 15), and had no focal neurological signs. Blood tests were unremarkable, in particular her white blood cell and neutrophil counts were within the normal range. A non-contrast computed tomography (CT) scan of the head was obtained in the emergency department (fig 1⇓).



Fig 1  Non-contrast computed tomography (CT) scan of the head: (A) axial and (B) sagittal views





### 1. What is the diagnosis based on the history and CT scan?

#### Short answer

Cerebral venous thrombosis, seen by the “dense triangle sign,” a hyperdensity at the posterior part of the superior sagittal sinus (fig 2a⇓), and the “cord sign” (fig 2b⇓), a homogenous hyperdensity that fills a sinus. Diagnosis is usually made from magnetic resonance (MR) or CT venography.



Fig 2  Non-contrast CT scan of the …
Assessment of cancer control capacity and readiness: the role of the International Atomic Energy Agency
Authors: May Abdel-Wahab, Beatrix Lahoupe, Alfredo Polo, Eduardo Zubizarreta, Raja R Adnan, Peter Johnston, Arsen Juric, Farid El Haffar, Mathias Andre, Ahmed Meghzifene
Journal: The Lancet Oncology (2017)
Medullary Thyroid Carcinoma—We Should Do Better
Authors: Jessica E. Gosnell, Quan-Yang Duh
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
CD205, a target antigen for a novel antibody drug conjugate (ADC): Evaluation of antigen expression on non-Hodgkin lymphoma (NHL).
Authors: Vincenzo Canzonieri, Valter Gattei, Michele Spina, Annalisa Polizzi-Anselmo, Nickolas Attanasio, Angelo Kaplan, Mario Bigioni, Giuseppe Merlino, Mariagiuseppa Matera, Silvia Manunta, Rachel Dusek, Christian Rohlff, Valentina Fedi, Monica Binaschi, Andrea Ugo Enrico Pellacani, Cecilia Simonelli
Journal: Journal of Clinical Oncology (2017)

e14039 Background: CD205 is a type I C-type lectin receptor normally expressed on various APC and some leukocyte sub-populations, characterized by a cytoplasmic domain containing protein motifs crucial for endocytosis and internalization. These features make CD205 ideal to be exploited as target of a novel ADC. MEN1309/OBT076 is a humanized IgG1 antibody against CD205, conjugated through a cleavable linker to a potent maytansinoid microtubule disruptor, DM4. Indeed, impressive results were obtained in high and low CD205 expressing xenografts for solid tumours and NHL. In vitro experimental model describing the by-stander effect of MEN1309 was implemented. Methods:A retrospective analysis to evaluate the CD205 expression on archival NHL biopsies was performed in the CRO-National Cancer Institute, Aviano IT. An immunohistochemistry (IHC) was performed on 1 slide per case, using a commercial antibody NCL-L-DEC205 (clone 11A10, Leica Biosystems). All slides were visually evaluated and a validated staining scoring system was applied, ranging from negative score 0 to strong immunostaining score 3+. Percentages (from 0 to 100%) of negative and positive tumor cells (scored as follows: 1-25% = score 1; 26-50% = score 2; 51-75% = score 3; 76-100% = score 4) were reported for each individual slide.Evaluation of correlations between CD205 expression and clinical characteristics is ongoing. Results: 100 cases of Diffuse Large B Cells Lymphomas (DLBCL) and 33 of Follicular Lymphomas (FL) were analysed. 60% of DLBCL cases were positive for CD205 and 39% had more than 25% of positive cells (score ≥2), while the 16% showed 2+/3+ staining intensity. 79% of FL cases were CD205 positive and 66% had more than 25% of positive cells, while the 27% showed 2+/3+ staining intensity. Conclusions: CD205 is heterogeneously expressed in the majority of DLBCL and FL cases. Data on the correlation between CD205 expression and clinical features will be discussed.MEN1309 has shown anti-tumour activity in vitro and in vivo even in low antigen expressing tumours. Hence CD205 expression among NHL, even if heterogeneous, makes, both DLBCL and FL, promising settings in which to explore MEN1309 activity in an upcoming FIH trial.
<scp>EAACI</scp> Guidelines on allergen immunotherapy: IgE‐mediated food allergy
Authors: G. B. Pajno, M. Fernandez‐Rivas, S. Arasi, G. Roberts, C. A. Akdis, M. Alvaro‐Lozano, K. Beyer, C. Bindslev‐Jensen, W. Burks, M. Ebisawa, P. Eigenmann, E. Knol, K. C. Nadeau, L. K. Poulsen, R. van Ree, A. F. Santos, G. du Toit, S. Dhami, U. Nurmatov, Y. Boloh, M. Makela, L. O'Mahony, N. Papadopoulos, C. Sackesen, I. Agache, E. Angier, S. Halken, M. Jutel, S. Lau, O. Pfaar, D. Ryan, G. Sturm, E.‐M. Varga, R. G. van Wijk, A. Sheikh, A. Muraro
Journal: Allergy (2017)

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.
An early report: a modified porphyrin-linked metronidazole targeting intracellular Porphyromonas gingivalis in cultured oral epithelial cells
Authors: Ping Ye, Jiho Chang, Lin Feng Foo, Benjamin C-M Yap
Journal: International Journal of Oral Science (2017)

Porphyromonas gingivalis (P. gingivalis) has a strong association with the pathogenesis of periodontal disease. Recurrence of periodontal disease following therapy is attributed to numerous factors, and of growing interest is the potential problem of intracellular bacteria that are able to persist and multiply within the host cell, thereby facilitating relapse of infection. The effect of antibiotic therapy in controlling P. gingivalis is questionable. Accordingly, while metronidazole is very effective against anaerobic extracellular P. gingivalis by disrupting the DNA of anaerobic microbial cells, this antibiotic does not effectively penetrate into mammalian cells to inhibit intracellular bacteria. Therefore in the present study, a modified porphyrin-linked metronidazole adducts, developed in our laboratory, was used to kill intracellular P. gingivalis. A series of experiments were performed, including cytotoxicity assays and cellular uptake of adducts by flow cytometry coupled with live cell imaging analysis, P. gingivalis invasion and elimination assays, and the analysis of colocalization of P. gingivalis and porphyrin-linked metronidazole by confocal laser scanning microscopy. Findings indicated that P. gingivalis and porphyrin-linked metronidazole were colocalized in the cytoplasm, and this compound was able to kill P. gingivalis intracellular with a sufficient culture time. This is a novel antimicrobial approach in the elimination of P. gingivalis from the oral cavity. A modified antibiotic has been shown to effectively get inside cells and kill bacteria that can cause gum disease to return after treatment. The bacterium Porphyromonas gingivalis is a cause of gum disease, and treatment with the antibiotic metronidazole is not completely effective. Metronidazole kills P. gingivalis but, unlike the bacteria, cannot get inside cells. P. gingivalis that consequently persists inside cells in the mouth after treatment is thought to contribute to recurrence of gum disease. In their new study, Ping Ye from the University of Sydney, Australia, and colleagues modified metronidazole with porphyrin, a molecule that enabled the antibiotic to enter cultured human mouth cells and target the bacteria. The modified antibiotic killed bacteria inside cells effectively, indicating that it could treat gum disease and prevent its recurrence.
Evaluating Molecular Biomarkers for the Early Detection of Lung Cancer: When Is a Biomarker Ready for Clinical Use? An Official American Thoracic Society Policy Statement
Authors: Peter J. Mazzone, Catherine Rufatto Sears, Doug A. Arenberg, Mina Gaga, Michael K. Gould, Pierre P. Massion, Vish S. Nair, Charles A. Powell, Gerard A. Silvestri, Anil Vachani, Renda Soylemez Wiener
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Section:ChooseTop of pageAbstract <<Executive SummaryContentsOverviewIntroductionMethodsBackgroundResultsDiscussion: Clinical Appl...ConclusionsAppendix 1: DefinitionsAppendix 2: Additional Re...ReferencesCITING ARTICLES
Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program
Authors: Patience Browne, Pamela D. Noyes, Warren M. Casey, David J. Dix
Journal: Environmental Health Perspectives (2017)

The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action.This review describes the EDSP's use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay.Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points.A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304.
Apolipoprotein E4 Impairs Neuronal Insulin Signaling by Trapping Insulin Receptor in the Endosomes
Authors: Na Zhao, Chia-Chen Liu, Alexandra J. Van Ingelgom, Yuka A. Martens, Cynthia Linares, Joshua A. Knight, Meghan M. Painter, Patrick M. Sullivan, Guojun Bu
Journal: Neuron (2017)