tbuckley/cabot-search huggingface dataset:
Clinical and demographic variables of young adult (YA) patients referred to inpatient supportive care.
Authors: Sujin Ann-Yi, Angelique Wong, Jimin Wu, Maira Charone, Karen Baumgartner, Cindy L. Carmack, Debra Castro, Diana Guzman, Manju P Joy, Leela Kuriakose, Kevin Madden, John M Najera, Imelda Pangemanan, Sabeena Qasim Rajani, Monica Raznahan, Holly A Stewart, Kimmie Tallie, Kimberson Cochien Tanco, Donna S. Zhukovsky, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

168 Background: Literature suggests that YA cancer patients have unique psychosocial issues and more emotional distress compared to older aged patients. Our study aimed to evaluate clinical and demographic factors of YA cancer patients that may impact physical and psychosocial symptom expression. Methods: A retrospective review was conducted on randomly selected patients seen during 2013-2015 of 3 age groups: 18-39 (YA), 40-64, and 65 and older on demographic, medical, psychosocial history, Morphine Equivalent Daily Dose (MEDD), Edmonton Symptom Assessment Scare (ESAS) scores, and Eastern Cooperative Oncology Group (ECOG) scores which are completed at time of initial consultation with the supportive care inpatient mobile team. Results: 896 (YA = 297, 40-64 cohort = 300, 65 and older = 299) patients were reviewed. YA cohort was associated with being female (n = 179 (60%), p = 0.03), more frequently non-white (Black and Hispanic = 124 (42%), p &lt; 0.00), higher ECOG scores (ECOG 0-2 = 83(39%), p &lt; 0.00) more psychiatric history (n = 95(32%), p = 0.00) and worse ESAS sleep scores (median = 6, p = 0.02). The YA cohort also had higher pain expression than the 65 and older cohort (p = .02). The YA group was more likely to have children younger than 18 years old (n = 171(58%), p &lt; 0.00). Patients with children less than 18 years of age reported higher pain expression (median = 6, p = .05), sleep (median = 6, p = 0.01), and financial distress (median = 2, p = 0.02). Conclusions: Contrary to other findings, YA cancer patients did not report higher symptoms or distress when compared to older age cohorts, with the exception of higher insomnia compared to other age cohorts and higher pain expression than the oldest age cohort. YA with young children reported higher level of pain, sleep and financial distress. Our findings suggest that the YA population may benefit from specialized psychosocial services to address their unique social needs, particularly to address concerns related to being parents of young children.
Molecular Characterization of Malignant Mesothelioma: Time for New Targets?
Authors: Charu Aggarwal, Steven M. Albelda
Journal: Cancer Discovery (2018)

Malignant pleural mesothelioma (MPM) is an aggressive lethal malignancy for which very few therapeutic options exist. In this issue of Cancer Discovery, Hmeljak and colleagues report on a comprehensive integrative analysis of histology-independent genomic characteristics of MPM. They confirm previous observations that inactivation of tumor suppressor genes is the predominant oncogenic mechanism. This study provides a scientific rationale for potentially novel therapeutic options, including immune-checkpoint targeting VISTA and small-molecule inhibitors targeting the epigenome, DNA-repair pathways, and aurora kinase.See related article by Hmeljak et al., p. 1548.
Patterns of anti-cancer therapy use in the last 14 days of life in a community cancer institute.
Authors: Caitlyn McNaughton, Selah Lynch, Kristina Braine Newport, Riley Wong, Sarah Svetec, Jason Moore, Rachel Holliday, Randall A. Oyer, Shanthi Sivendran
Journal: Journal of Clinical Oncology (2018)

66 Background: Studies have shown that aggressive cancer care at end of life is associated with decreased quality of life, decreased median survival, and increased cost of care. This study describes the patients most likely to receive aggressive anti-cancer therapy at the end of life in a community cancer institute. Methods: We performed a retrospective review of 213 patients who received anti-cancer therapy in our institution and died between July 2016-April 2017. Data collected included primary malignancy, death date, date of last anti-cancer treatment, hospice enrollment, healthcare utilization, Oncology Care Model (OCM) enrollment, and clinical assessments at last office visit prior to a treatment decision before death. Data were analyzed using univariate logistic regression to determine feature importance. Results: Of the 201 patients who died of cancer, 36 (17%) received anti-cancer therapy within the last 14 days of life. Several factors were significantly positively correlated with receiving anti-cancer therapy at end of life, including enrollment in OCM (p &lt; 0.001), frequency of hospital utilization (p &lt; 0.001), death in hospital (p&lt;0.001), referral to hospice (p&lt;0.001), and hematologic malignancy (p = 0.014). Conclusions: In our community cancer institute, enrollment in OCM, frequency of hospitalizations, death in a hospital, referral to hospice, and hematologic malignancy diagnosis were predictive of receiving aggressive anticancer therapy at the end of life, suggesting that these factors should have greater importance in our clinic. Taken as a whole, these data will help inform clinicians and patients in choices regarding care near the end of life.
Disease-modifying therapies for multiple sclerosis
Authors: Floriana De Angelis, Nevin A John, Wallace J Brownlee
Journal: BMJ (2018)

### What you need to know

A 32 year old woman with multiple sclerosis presented to her general practitioner with a five day history of numbness and weakness in the right leg. She felt well in herself and did not describe any symptoms to suggest an intercurrent infection. She had been taking weekly intramuscular injections of interferon beta-1a for the previous 18 months and reported flu-like symptoms that could last for up to 24 hours after each dose. She asked if there was a need to change her treatment and what alternatives were available. 

Multiple sclerosis is a chronic, immune-mediated, demyelinating disorder of the central nervous system affecting over two million people worldwide.1 It is a major cause of physical disability in young adults and can have profound implications for cognition, emotional wellbeing, and employment. Patients commonly present with unilateral visual loss (due to optic neuritis), double vision, sensory symptoms, limb weakness, or imbalance.2 The diagnosis is based on clinical features and findings on magnetic resonance imaging (MRI), sometimes supported by lumbar puncture and other investigations.23

Nearly 80-85% of people with multiple sclerosis experience a relapsing course: episodes (attacks or relapses) of new or worsening neurological symptoms lasting at least 24 hours, followed by full or partial recovery, in the absence of fever or infection (fig 1).3 If left untreated, most people with relapsing multiple sclerosis develop disability over time. This can …
Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA (ctDNA) in metastatic breast cancer.
Authors: Charlotte Victoria Fribbens, Isaac Garcia-Murillas, Matthew Beaney, Sarah Hrebien, Karen Howarth, Michael Epstein, Nitzan Rosenfeld, Alistair E. Ring, Stephen R. D. Johnston, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2017)

1015 Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have a high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Methods: Seventy-one patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study to collect plasma samples for ctDNA analysis every three months on therapy, and at disease progression. All plasma samples were analysed with ESR1 multiplex digital PCR assays, and samples at disease progression were analysed by InVision (enhanced tagged-amplicon sequencing). Mutations were tracked back through samples prior to disease progression to study the evolution of mutations on therapy. Results: Of the 34 patients who progressed on first line AI, 53% (18/34) had ESR1 mutations detectable at progression. Sequencing of progression plasma ctDNA identified polyclonal RAS mutations in 10.7% (3/28) progressing patients (2 polyclonal KRAS, 1 monoclonal HRAS), all of whom also had ESR1 mutations, and a patient with an activating p.R248C FGFR3 mutation. ESR1 mutations were subclonal in 78.6% (11/14) patients, with all RAS mutations being rare subclones. In serial tracking prior to progression, ESR1 mutations were detectable in plasma with a median of 5.3 months (95% CI 2.9-NA) prior to clinical progression. Conclusions: ESR1 mutations are found at high frequency in patients progressing on AI, but are frequently sub-clonal and may not be the sole driver of AI resistance in these patients. Poly-clonal KRAS mutations are identified as a novel mechanism of resistance to AI, associated with detection of ESR1 mutations.
Abstract 17409: Therapeutic Inhibition of RIP1 Improves Metabolic Dysfunction and Inhibits Atherosclerosis in Mouse Models of Cardiometabolic Diseases
Authors: Denuja Karunakaran, Michele Geoffrion, My Anh Nguyen, Lister Zachary, Joshua Kandiah, Ana Mompeon, Hailey Wyatt, Adam Turner, Majid Nikpay, Ella deKemp, Calvin Pan, Mary-Ellen Harper, Aldons Lusis, Ruth McPherson, Richard Lee, Katey J Rayner
Journal: Circulation (2017)

Introduction: Chronic activation of the innate immune system drives inflammation and contributes directly to obesity, insulin resistance and atherosclerosis. Previously we showed that necroptosis, ...
Evaluation of the in vivo efficacy, toxicity and lymphatic drainage of loco-regional administered polymer-lipid hybrid nanoparticles (PLN) loaded with doxorubicin in a murine solid tumor model
Authors: Toshiyuki Shimada, Masakazu Ueda, Hiromitsu Jinno, Seiichiro Ishii, Tadashi Ikeda, Junji Watanabe, Kazuhiro Ishihara, Masaki Kitajima
Journal: Cancer Research (2006)

3070  Background: aclitaxel (PTX) is hardly soluble in water. Therefore, PTX is used with Cremophor EL (CrEL) to enhance its solubility. Because of the content of CrEL, however, serious hypersensitivity reaction and neuropathy have been reported. On the other hand, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer is water-soluble and biocompatible. As it can stably incorporate hydrophobic materials, it is available for the transporter of PTX. In addition, it may prevent some unfavorable effects resulting from the addition of CrEL. Epidermal growth factor receptor (EGFR) overexpression is correlated with a poor prognosis in cancer patients. As one element of a multidisciplinary treatment, we have developed targeted therapy aimed at EGFR. We also reported that the cytotoxicity of PTX incorporated in EGF-Conjugated MPC polymer against EGFR overexpression cell lines (A431 and BT-20) was significantly higher than that of PTX incorporated in MPC polymer. In this study, we investigated the antitumor effect of PTX incorporated in EGF-conjugated MPC polymer against cancer with EGFR overexpression. Materials and methods: MBN was dissolved in PBS containing EGF and agitated for 2 days at 4°C. After removing p-nitrophenol by dialysis, EGF-conjugated PMBN was obtained. PTX dissolved in ethanol was added to MPC polymer aqueous solution, followed by vortexing of the mixture solution. The ethanol was removed by evaporation to prepare PTX incorporated in EGF-conjugated PMBN (PTX-PMBN-EGF). PTX in unconjugated PMBN (PTX-PMBN) was also prepared. EGFR-overexpressing squamous carcinoma cells (A431) (106/site) were injected into nude mice s.c. in the bilatero-abdominal region. After the tumor volume reached 100 mm3, PTX-PMBN-EGF, PTX-PMBN, PTX and saline were injected i.p. for 5 consecutive days. All reagents except saline contained PTX at the concentration of 15mg/kg. Results: he growth of A431 cell tumor in mice was inhibited by PTX-PMBN-EGF, PTX-PMBN and PTX. The growth inhibitory rates at 21days after treatment were 97.4%, 70.4% and 69.2%, respectively. The growth inhibitory rate of PTX-PMBN-EGF was significantly higher than that of PTX-PMBN. There was no significant difference in the survival time between PTX-PMBN-EGF group and PTX-PMBN group. No adverse effects including weight loss were observed in every group. Conclusion: hese results suggested that Paclitaxel incorporated in EGF-conjugated MPC polymer may represent a potent targeted therapy for cancer with EGFR overexpression.
The Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) ERS Clinical Research Collaboration: a new dawn in asthma research
Authors: Ratko Djukanovic, Ian M. Adcock, Gary Anderson, Elisabeth H. Bel, Giorgio W. Canonica, Hui Cao, Kian Fan Chung, Donna E. Davies, Céline Genton, Toni Gibson-Latimer, Dominique Hamerlijnck, Elise Heuvelin, Renaud Louis, Stephanie Korn, Maxim Kots, Namhee Kwon, Riad Naddaf, Scott S. Wagers
Journal: European Respiratory Journal (2018)

<b>SHARP (Severe Heterogeneous Asthma Research collaboration, Patient-centred) is set up to harmonise severe asthma management across Europe and unravel the heterogeneity of severe asthma in a patient-centred way</b>http://ow.ly/s1x730mwLpk
What should be in hospital doctors' continuing professional development?
Authors: Lorelei Jones, Fiona Moss
Journal: Journal of the Royal Society of Medicine (2018)

Objective To ask those most affected by continuing professional development for senior doctors – patients, other professional groups and doctors themselves – what it needs to encompass. Design The nominal group technique. Participants Six groups of between seven and nine members (n = 49). Separate groups were held for nurses and therapists (n = 9), patient representatives (n = 8), medical directors (n = 8), consultants (n = 8) and medical trainees (n = 7). An additional group consisted of ‘Darzi Fellows’ (n = 9), trainee doctors who were undertaking a leadership fellowship. Setting Groups were held at the Royal Society of Medicine in London. Main outcome measures Priorities for the content of continuing professional development for senior hospital doctors, ranked in order of importance. Themes derived from analysis of group discussions. Results We present the ranked priorities of different groups for what should be included in continuing professional development for senior hospital doctors. Analysis of group discussions identified the following three themes: developing and supporting the system of care; changes in the way medicine is practised; and personal wellbeing and caring for colleagues. Conclusions The implication of our findings for providers of continuing professional development is to consider the balance of content. Doctors and other healthcare professionals need to keep up with scientific advances and technical developments. But in addition, they need to be adept at working with the system changes required for translation of research into practice, the development of new ways of working, and for the organisational changes that underpin continual quality and safety improvement.
Characterising the respiratory microbiome
Authors: Rebecca L. Watson, Emma M. de Koff, Debby Bogaert
Journal: European Respiratory Journal (2018)

<b>Studying the respiratory microbiome provides critical novel insights into respiratory disease pathogenesis which may improve clinical management, and we should strive to standardise study design, laboratory procedures and statistical methods in the field</b>http://ow.ly/qNF330mWrEK
An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia
Authors: Toshiro Saito, Jihoon Nah, Shin-ichi Oka, Risa Mukai, Yoshiya Monden, Yasuhiro Maejima, Yoshiyuki Ikeda, Sebastiano Sciarretta, Tong Liu, Hong Li, Erdene Baljinnyam, Diego Fraidenraich, Luke Fritzky, Peiyong Zhai, Shizuko Ichinose, Mitsuaki Isobe, Chiao-Po Hsu, Mondira Kundu, Junichi Sadoshima
Journal: Journal of Clinical Investigation (2018)

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of trans-Golgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria.
Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
Authors: Xianjun Dong, Zhixiang Liao, David Gritsch, Yavor Hadzhiev, Yunfei Bai, Joseph J. Locascio, Boris Guennewig, Ganqiang Liu, Cornelis Blauwendraat, Tao Wang, Charles H. Adler, John C. Hedreen, Richard L. M. Faull, Matthew P. Frosch, Peter T. Nelson, Patrizia Rizzu, Antony A. Cooper, Peter Heutink, Thomas G. Beach, John S. Mattick, Ferenc Müller, Clemens R. Scherzer
Journal: Nature Neuroscience (2018)
Third-generation cephalosporin and carbapenem resistance in Streptococcus mitis/oralis. Results from a nationwide registry in the Netherlands
Authors: J. van Prehn, M.I. van Triest, W. Altorf-van der Kuil, K. van Dijk, J.W.T. Cohen Stuart, A.J.L. Weersink, K. van Dijk, D. Notermans, M.L. van Ogtrop, M.M. Jager, B.F.M. Werdmuller, B.C. van Hees, P.H.J. van Keulen, J. Alblas, W. Altorf-van der Kuil, L. Blijboom, S.C. de Greeff, S. Groenendijk, J. van Heereveld, R. Hertroys, J.C. Monen, D.W. Notermans, E.A. Reuland, A.F. Schoffelen, M.I. van Triest, C.C.H. Wielders, S.H.S. Woudt, P.H.J. van Keulen, J.A.J.W. Kluytmans, E.M. Kraan, E.E. Mattsson, F.W. Sebens, E. de Jong, H.M.E. Frénay, B. Maraha, A.J. van Griethuysen, A. Demeulemeester, B.B. Wintermans, M. van Trijp, A. Ott, None E. Bathoorn, M. Lokate, J. Sinnige, A.J.L. Weersink, E.I.G.B. de Brauwer, F.S. Stals, W. Silvis, L.J. Bakker, J.W. Dorigo-Zetsma, B. Ridwan, K. Waar, A.T. Bernards, S.P. van Mens, N. Roescher, M.H. Nabuurs-Franssen, H. Wertheim, B.M.W. Diederen, L. Bode, M. van Rijn, S. Dinant, O. Pontesilli, P. de Man, M.A. Leversteijn-van Hall, E.P.M. van Elzakker, A.E. Muller, N.H. Renders, D.W. van Dam, B.M.W. Diederen, A.G.M. Buiting, A.L.M. Vlek, A. Reuland, F.N.J. Frakking, I.T.M.A. Overdevest, R.W. Bosboom, T. Trienekens, G.J.H.M. Ruijs, M.J.H.M. Wolfhagen
Journal: Clinical Microbiology and Infection (2018)
Scheme to train overseas doctors in the NHS will expand, says newspaper report
Authors: Abi Rimmer
Journal: BMJ (2018)

A scheme that allows doctors from outside the European Union to live and train in the UK before returning home is set to be expanded, the Guardian has reported.

The newspaper reported on 29 November that the number of non-EU doctors allowed to enter the UK as part of the medical training initiative (MTI) would be increased to as many as 3000, up from the 1000 places currently available.1

The MTI was launched by the health department in 2009, and 3950 doctors have been through it. Under the current …
Chemical coping and efficacy of buprenorphine for cancer pain.
Authors: Amy Allen Case, Eric Hansen, Chitra Nadagoundla, Chong Wang
Journal: Journal of Clinical Oncology (2018)

200 Background: The management of cancer-related pain is challenging in the age of the opioid epidemic. Patients who struggle with substance misuse or chemical coping use these substances to dull emotional and or existential suffering. Buprenorphine is often used for cancer pain due to less reported euphoria when compared to other opioids. Methods: We conducted a retrospective review of patients in an outpatient palliative care clinic at a tertiary comprehensive cancer center who were prescribed buprenorphine for cancer pain. Total oral morphine equivalent (OME), as well as use of adjuvant non-opioid neuropathic pain medication, were assessed prior to transition to buprenorphine. Chemical coping behavior was defined as patients taking opioids for emotional pain in excess of the maximum prescribed amount. Pain scores were reported before and after buprenorphine administration using a Likert pain scale (0-10). Patients were also assessed for the presence of withdrawal symptoms after transition to buprenorphine. Results: Patients were predominantly female (75%), slightly more than half had a psychiatric diagnosis (56%), a majority were on non-opioid neuropathic pain medication (93%), and the majority were identified as chemical copers (75%). For all patients, the mean pain score prior to buprenorphine (pain pre) was 8.3 and the mean pain score on follow up post buprenorphine (pain post) was 6.1, with a reduction in mean pain score (pain change) of -2.0 (p = 0.059). Patients without chemical coping behaviors reported a significantly greater reduction in pain scores compared to patients with chemical coping (pain change -5.0 vs -1.3, p = 0.02). Illicit drug use and psychiatric co-morbidity were not associated with differences in reported pain scores. Only a small number of patients reported withdrawal symptoms (6%) during buprenorphine transition. Conclusions: Rotation to buprenorphine led to a trend of reduction in pain score, though not statistically significant. Patients without chemical coping experienced greater reductions in pain score than those with chemical coping behavior. Illicit drug use and psychiatric co-morbidity were not associated with differences in reported pain.
Treatment Regimens for Patients with Newly Diagnosed Multiple Myeloma Who Are Ineligible for Stem Cell Transplantation: A Systematic Literature Review and Network Meta-Analysis
Authors: Jesus F San-Miguel, Thierry Facon, Meletios A Dimopoulos, Maria-Victoria Mateos, Michele Cavo, Bart Heeg, Sophie van Beekhuizen, Marta Pisini, Sandhya Nair, Annette Lam, Mary Slavcev
Journal: Blood (2018)
Impact of Checkpoint Inhibitor Pneumonitis on Survival in NSCLC Patients Receiving Immune Checkpoint Immunotherapy
Authors: Karthik Suresh, Kevin J. Psoter, Khinh Ranh Voong, Bairavi Shankar, Patrick M. Forde, David S. Ettinger, Kristen A. Marrone, Ronan J. Kelly, Christine L. Hann, Benjamin Levy, Josephine L. Feliciano, Julie R. Brahmer, David Feller-Kopman, Andrew D. Lerner, Hans Lee, Lonny Yarmus, Russell K. Hales, Franco D’Alessio, Sonye K. Danoff, Jarushka Naidoo
Journal: Journal of Thoracic Oncology (2018)
JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition
Authors: Anna Sophia McKenney, Allison N. Lau, Amritha Varshini Hanasoge Somasundara, Barbara Spitzer, Andrew M. Intlekofer, Jihae Ahn, Kaitlyn Shank, Franck T. Rapaport, Minal A. Patel, Efthymia Papalexi, Alan H. Shih, April Chiu, Elizaveta Freinkman, Esra A. Akbay, Mya Steadman, Raj Nagaraja, Katharine Yen, Julie Teruya-Feldstein, Kwok-Kin Wong, Raajit Rampal, Matthew G. Vander Heiden, Craig B. Thompson, Ross L. Levine
Journal: Journal of Clinical Investigation (2018)