tbuckley/cabot-search huggingface dataset:
Whole-brain radiation practice pattern at a tertiary hospital with high-volume radiosurgery practice.
Authors: Lauren Boreta, Emily Yee, Susan Y. Wu, Steve E. Braunstein
Journal: Journal of Clinical Oncology (2019)

113 Background: Whole brain radiation (WBRT) is standard therapy used for palliation of brain metastases (BM). SRS is also used as primary treatment in patients with multiple BM, with WBRT reserved for salvage. We sought to describe WBRT practice patterns at a tertiary cancer center with a high-volume radiosurgical practice, and hypothesized that patients treated with WBRT at our institution had limited survival. Methods: Retrospective chart review was performed for patients treated with WBRT for BM from January 2013-Jan 2019. Patients with complete records were included in the analysis. Mann-Whitney U and chi-squared tests were for comparison of clinical factors. Results: Data for 100 patients receiving WBRT were available for analysis. Patients had NSCLC (32%) breast cancer (30%) and melanoma (9%). Median age was 52 (IQR 23). 43% of patients had SRS prior to WBRT, and 41% had 2+ SRS treatments prior to WBRT. 44% of patients had WBRT only. Median survival from diagnosis of BM was 9.3 months (IQR 17.9) and median survival from WBRT was 2.7 months (IQR 11.3). 35% of patients died within 30 days of WBRT, and 3% of patients died on treatment. 77% of patients had uncontrolled extracranial metastases and 43% of patients had imaging evidence of leptomeningeal disease (LMD). Of those with documented cause of death, 65% of patients with LMD died of neurologic causes, compared with 22% of those without LMD (p &lt; 0.001). Patients with KPS &lt; 70 had median survival of 2 months after WBRT, compared with 3.7 months in those with KPS &gt; 70. Patients treated with WBRT alone and those treated with salvage WBRT after SRS had median survival after WBRT of 2.1 months, however median survival from time of brain met diagnosis was 3.3 months in those treated with WBRT alone, versus 12.8 months in those treated with salvage WBRT (p &lt; 0.0001). Conclusions: This study reveals the poor prognosis of patients requiring WBRT at a tertiary cancer center. 35% patients died within 30 days of WBRT, in contrast to a prior study demonstrating 10% 30-day mortality after SRS, owing to differences in patient selection. The potential for poor outcome should be discussed with patients during shared-decision making, balancing toxicity or futility with potential benefits of treatment.
KDM6B Overexpression and TET2 Deficiency Cooperatively Drive Development of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia-like Phenotype in Mice
Authors: Yue Wei, Hong Zheng, Naran Bao, Rashmi Kanagal-Shamanna, Caleb Class, Hui Yang, Guillermo Montalban Bravo, Irene Ganan-Gomez, Kelly Soltysiak, Kim-Ann Do, Simona Colla, Carlos E. Bueso-Ramos, Guillermo Garcia-Manero
Journal: Blood (2019)
Randomized trial of prophylactic minocycline for erlotinib-associated skin rash in non-small cell lung cancer (PEARL trial)
Authors: K. Kusaka, A. Tamura, T. Kozuki, Y. Koreeda, T. Kita, T. Endo, T. Shibayama, N. Hatakeyama, M. Miura, N. Yamashita, M. Takenoyama
Journal: Annals of Oncology (2019)
Clonal Selection Drives NF-κB Activation in Recurrent Nasopharyngeal Carcinoma
Authors: Kartik Sehgal, David A. Barbie
Journal: Cancer Research (2019)

Abstract Cancer genomic profiling has improved our understanding of the key drivers of tumor development, clonal evolution, and recurrence, and aided precision medicine efforts to eradicate therapy-resistant cancer cell clones. In this issue, You and colleagues report these results for recurrent nasopharyngeal carcinoma, an aggressive malignancy associated with poor outcomes with recurrent disease. They identify a crucial contributory role of clonal NF-κB activating mutations in pathogenesis of recurrence in this cancer and provide a promising target for combinatorial therapeutic approaches. See related article by You et al., p. 5930
Antigenic competition in CD4 <sup>+</sup> T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial
Authors: Esper G. Kallas, Nicole A. Grunenberg, Chenchen Yu, Bryce Manso, Giuseppe Pantaleo, Martin Casapia, Lindsey R. Baden, Javier Valencia, Magdalena Sobieszczyk, Hong Van Tieu, Mary Allen, John Hural, Barney S. Graham, James Kublin, Peter B. Gilbert, Lawrence Corey, Paul A. Goepfert, M. Juliana McElrath, R. Paul Johnson, Yunda Huang, Nicole Frahm
Journal: Science Translational Medicine (2019)

T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.
Abstract 11123: Intermittent Fasting Lifestyle and Human Longevity in Cardiac Catheterization Populations
Authors: Benjamin D Horne, Ciera Bartholomew, Jeffrey L Anderson, Heidi T May, Kirk U Knowlton, Tami L Bair, Viet T Le, Bruce W Bailey, Joseph B Muhlestein
Journal: Circulation (2019)

Introduction: Since a rodent study of intermittent fasting (IF) and survival in 1946, animal models have repeatedly shown IF increases longevity. Human data, though, are limited to anecdotal longev...
PTH-093 Outcomes following the introduction of week 12 anti-tnf drug and antibody testing in patients with inflammatory bowel disease
Authors: A Boal, SI Squires, GD Naismith
Journal: Gut (2017)

Introduction  The use of anti-TNF drug and antibody testing has increased in clinical practice. Recent NICE guidance has advocated further research into clinical outcomes associated with testing. This report describes outcomes following the introduction of drug level and antibody testing (TDM) to our 12 week assessment criteria in treatment naive patients.  Method  In July 2015 the Royal Alexandra and Vale of Leven Hospitals introduced TDM as part of the clinical assessment of all patients commencing anti-TNF therapy. Those with previous anti-TNF exposure were excluded. Between July 2015 and December 2016, Infliximab (IFx) and Adalimumab (ADA) levels were measured at week 12. 54 patients commenced ADA (37 Crohns vs 17 Ulcerative Colitis) and 20 commenced IFx (7 Crohn’s disease vs 13 Ulcerative Colitis). In total 74 patients had TDM checked, in addition to symptom assessment and CRP measurement. The results were sub-categorised to determine patients with drug levels greater than or equal to 3 µg/mL [Group 1- therapeutic], less than 3 µg/mL, but greater than 0.8 µg/mL [Group 2-subtherapeutic] and less than 0.8 µg/mL [Group 3-undetectable].  Results  Group 1 had 62/74 (84%) with therapeutic levels. 3/62 (5%) developed antibodies. 54/62 (87%) reported good symptom control. There was a reduction in mean CRP of 87% over 12 weeks. 8/62 (13%) were symptomatic at week 12 and assessment by colonoscopy determined active disease, despite therapeutic levels.  Group 2 had 4/74 (5%) with subtherapeutic levels. 1/4 (25%) developed antibodies. 1/4 (25%) had dose increase in therapy. 1/4 (25%) had therapy withdrawn (in remission). 2/4 (50%) were maintained on current dose. There was a reduction in mean CRP of 24% over 12 weeks.  Group 3 had 8/44 (11%) with undetectable levels. 6/8 (75%) developed antibodies. 4/8 (50%) were withdrawn from treatment following assessment. 4/8 (50%) had active disease on colonoscopy and had a change of biological agent. There was a reduction in mean CRP by 20% over 12 weeks  Conclusion  At 12 weeks 16% of patients in this cohort had sub therapeutic or undetectable drug levels. This prompted further assessment, which facilitated either an early switch of therapy or treatment withdrawal. There is a lower level of antibody formation in the therapeutic and subtheraputic groups and greater reduction in CRP in the therapeutic group. 12 week TDM measurement appears to be a worthwhile addition to standard assessment.  Disclosure of Interest  None Declared
Neuronal impact of patient-specific aberrant NRXN1α splicing
Authors: Erin Flaherty, Shijia Zhu, Natalie Barretto, Esther Cheng, P. J. Michael Deans, Michael B. Fernando, Nadine Schrode, Nancy Francoeur, Alesia Antoine, Khaled Alganem, Madeline Halpern, Gintaras Deikus, Hardik Shah, Megan Fitzgerald, Ian Ladran, Peter Gochman, Judith Rapoport, Nadejda M. Tsankova, Robert McCullumsmith, Gabriel E. Hoffman, Robert Sebra, Gang Fang, Kristen J. Brennand
Journal: Nature Genetics (2019)
Quantitative chimerism in CD3-negative mononuclear cells predicts prognosis in acute myeloid leukemia patients after hematopoietic stem cell transplantation
Authors: Anne Bouvier, Jérémie Riou, Sylvain Thépot, Aurélien Sutra Del Galy, Sylvie François, Aline Schmidt, Corentin Orvain, Marie-Hélène Estienne, Alban Villate, Damien Luque Paz, Laurane Cottin, Bénédicte Ribourtout, Annaëlle Beucher, Yves Delneste, Norbert Ifrah, Valérie Ugo, Mathilde Hunault-Berger, Odile Blanchet
Journal: Leukemia (2019)
Sequential Matrix-RICE Therapy Followed By Autologous Stem Cell Transplant in Patients with Diffuse Large B-Cell Lymphoma and Secondary Central Nervous System Involvement: The International Extranodal Lymphoma Study Group-42 Phase II (MARIETTA) Trial
Authors: Andres JM Ferreri, Jeanette K. Doorduijn, Chiara Cattaneo, Maria Giuseppina Cabras, Jeffery Smith, Fiorella Ilariucci, Franco Narni, Teresa Calimeri, Alessandro Re, Jahanzaib Khwaja, Barbara Botto, Claudia Cellini, Luca Nassi, Kim Linton, Pam McKay, Jacopo Olivieri, Caterina Patti, Francesca Re, Alessandro Fanni, Vikram Singh, Jacoline Bromberg, Kelly Cozens, Elisabetta Gastaldi, Nicola Cascavilla, Andrew Davies, Christopher P Fox, Maurizio Frezzato, Wendy Osborne, Anna Marina Liberati, Urban Novak, Renato Zambello, Emanuele Zucca, Kate Cwynarski
Journal: Blood (2019)
Integrative systematic review meta-analysis and bioinformatics identifies MicroRNA-21 and its target genes as biomarkers for colorectal adenocarcinoma
Authors: Narjes Saheb Sharif-Askari, Fatemeh Saheb Sharif-Askari, Salman Yousuf Guraya, Riyad Bendardaf, Rifat Hamoudi
Journal: International Journal of Surgery (2019)

Advanced colorectal has poor survival and are difficult to treat. Therefore, there is an urgent need for biomarkers to diagnose this cancer at earlier manageable stages. Micro-RNAs (miRNAs) are amongst the most significant biomarkers that have shown promise in improving management and early detection of different types of cancers. However, since MiRNAs are non-coding, the main limitation of using them as biomarkers is that they do not have associated phenotype and therefore difficult to validate using other techniques. This makes it difficult to understand the mechanism of miRNA is disease initiation and progression, therefore any methodology that can provide semantics to miRNA expression would enhance the understanding of the role of miRNA in disease.Here we report an integrative meta-analysis and bioinformatics methodology that showed microRNA-21 and its associated target mRNA to be the most significant predictive biomarkers for colorectal adenoma and adenocarcinoma. After drawing key inferences by meta-analysis, the authors then developed a bioinformatics method to identify mir-21 gene targeting in a specific tissue using two different bioinformatics approaches; absolute GSEA (Gene Set Enrichment Analysis) and LIMMA (Linear Models for MicroArray data) to identify differentially expressed genes of miRNA-21.Results from GSEA intersection with mir-21 gene targets was a subset of longer gene list that was obtained from the GEO2R intersect. In our study, both of longer GEO2R gene target list and the more focused GSEA list established the fact that mir-21 target numerous functional pathways that are mostly interconnected. Our three steps bioinformatics approach identified ABCB1, HPGD, BCL2, TIAM1, TLR3, and PDCD4 as common targets for mir-21 in both of adenoma as well as adenocarcinoma suggesting they are biomarkers for early CRC.The approach in this study proposed combining the big data from the scientific literature together with novel bioinformatics to bring about a methodology that can be used to first identify which microRNAs are involved in a specific disease, and then to identify a panel of biomarkers derived from the microRNAs target genes, and from these target genes the functional significance of these microRNAs can be inferred providing better clinical value for the surgeon.
Bupropion: a new treatment for smokers
Authors: John Britton, Martin J Jarvis
Journal: BMJ (2000)

Bupropion was licensed in June by the Medicines Control Agency for use in the United Kingdom to help patients stop smoking. Bupropion is the first new pharmacological treatment for smokers to be introduced since nicotine replacement therapy 20 years ago. Bupropion can potentially have a huge impact on public health not only through the efficacy of the drug itself but also by making smoking cessation services more widely available.

There are about 13 million regular smokers in the United Kingdom.1 One in every two lifelong smokers will die prematurely from tobacco related causes.2 Interventions to help people stop smoking are cost effective in preventing that premature loss of life, and nicotine replacement products are the most effective treatment available.3 4 About 20% of those given nicotine replacement with support from specialist counsellors will remain non-smokers for one year and up to about 10% will remain non-smokers if given brief advice from a health professional in addition to nicotine replacement.3 This latter approach may potentially have a far greater impact on public health because wider coverage of the population can be achieved. It is also cost effective.5 However, nicotine replacement and counselling services …
HIV among women in the WHO European Region – epidemiological trends and predictors of late diagnosis, 2009-2018
Authors: Otilia Mårdh, Chantal Quinten, Giorgi Kuchukhidze, Nicole Seguy, Masoud Dara, Andrew J Amato-Gauci, Anastasia Pharris
Journal: Eurosurveillance (2019)

Human immunodeficiency virus (HIV) transmission among women remains an issue in the WHO European Region, with nearly 50,000 women diagnosed in 2018 and over half (54%) diagnosed late. Although new HIV diagnoses declined between 2009 and 2018 in the West of the Region, they increased in the Centre and East. Understanding the characteristics of women diagnosed with HIV can inform gender-sensitive prevention services including pre-exposure prophylaxis and early testing and linkage to care.
Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions
Authors: Marc Hilmi, Cindy Neuzillet, Julien Calderaro, Fouad Lafdil, Jean-Michel Pawlotsky, Benoit Rousseau
Journal: Journal for ImmunoTherapy of Cancer (2019)

Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide, due to its high incidence and poor prognosis. Frequent initial presentation at advanced stages along with impaired liver function limit the use of a broad therapeutic arsenal in patients with HCC. Although main HCC oncogenic drivers have been deciphered in recent years (<i>TERT, TP53, CTNNB1 mutations, miR122 and CDKN2A silencing</i>), therapeutic applications derived from this molecular knowledge are still limited. Given its high vascularization and immunogenicity, antiangiogenics and immune checkpoint inhibitors (ICI), respectively, are two therapeutic approaches that have shown efficacy in HCC. Depending on HCC immune profile, combinations of these therapies aim to modify the protumoral/antitumoral immune balance, and to reactivate and favor the intratumoral trafficking of cytotoxic T cells. Combination therapies involving antiangiogenics and ICI may be synergistic, because vascular endothelial growth factor A inhibition increases intratumoral infiltration and survival of cytotoxic T lymphocytes and decreases regulatory T lymphocyte recruitment, resulting in a more favorable immune microenvironment for ICI antitumoral activity. First results from clinical trials evaluating combinations of these therapies are encouraging with response rates never observed before in patients with HCC. A better understanding of the balance and interactions between protumoral and antitumoral immune cells will help to ensure the success of future therapeutic trials. Here, we present an overview of the current state of clinical development of antitumoral therapies in HCC and the biological rationale for their use. Moreover, translational studies on tumor tissue and blood, prior to and during treatment, will help to identify biomarkers and immune signatures with predictive value for both clinical outcome and response to combination therapies.
In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography
Authors: Kamel Madi, Katherine A. Staines, Brian K. Bay, Behzad Javaheri, Hua Geng, Andrew J. Bodey, Sarah Cartmell, Andrew A. Pitsillides, Peter D. Lee
Journal: Nature Biomedical Engineering (2019)
Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria
Authors: Ignacio Matos, Juan Martin-Liberal, Alonso García-Ruiz, Cinta Hierro, Maria Ochoa de Olza, Cristina Viaplana, Analia Azaro, Maria Vieito, Irene Braña, Gemma Mur, Javier Ros, Jose Mateos, Guillermo Villacampa, Roger Berché, Mafalda Oliveira, Maria Alsina, Elena Elez, Ana Oaknin, Eva Muñoz-Couselo, Joan Carles, Enriqueta Felip, Jordi Rodón, Josep Tabernero, Rodrigo Dienstmann, Raquel Perez-Lopez, Elena Garralda
Journal: Clinical Cancer Research (2019)

Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon.We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response.Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1-treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97-6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53-10.12; HR = 1.73, 95% CI, 1.05-2.85; P = 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07-6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88-8.67) were not statistically significant (HR 1.4, 95% IC, 0.70-2.77; P = 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs.HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice.
Intensity and quality of exertional dyspnoea in patients with stable pulmonary hypertension
Authors: Athénaïs Boucly, Capucine Morélot-Panzini, Gilles Garcia, Jason Weatherald, Xavier Jaïs, Laurent Savale, David Montani, Marc Humbert, Thomas Similowski, Olivier Sitbon, Pierantonio Laveneziana
Journal: European Respiratory Journal (2019)

Dynamic hyperinflation is observed during exercise in 60% of patients with clinically stable pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), intensifying exertional dyspnoea. The impact of dynamic changes in respiratory mechanics during exercise on qualitative dimensions of dyspnoea in these patients has not been evaluated.26 patients (PAH n=17; CTEPH n=9) performed an incremental symptom-limited cycle exercise test. Minute ventilation (V'E), breathing pattern, operating lung volumes and dyspnoea intensity were assessed throughout exercise. Dyspnoea quality was serially assessed during exercise using a three-item questionnaire (dyspnoea descriptors). The inflection point of tidal volume (VT) relative to V'E was determined for each incremental test. Changes in inspiratory capacity during exercise defined two groups of patients: hyperinflators (65%) and non-hyperinflators (35%). Multidimensional characterisation of dyspnoea was performed after exercise using the Multidimensional Dyspnea Profile.In hyperinflators, inspiratory capacity decreased progressively throughout exercise by 0.36 L, while remaining stable in non-hyperinflators. The "work/effort" descriptor was most frequently selected throughout exercise in both types of patients (65% of all responses). At the VT/V'E inflection, work/effort plateaued while "unsatisfied inspiration" descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the VT/V'E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the VT/V'E inflection may have important implications for symptom management in patients with pulmonary hypertension.
David Oliver: Do public campaigns relieve pressure on emergency departments?
Authors: David Oliver
Journal: BMJ (2019)

For several years the NHS has issued public campaigns urging people to use alternatives to hospital emergency departments. We have a growing problem with overcrowding, in departments that were often built for smaller numbers of patients attending and are struggling with staffing gaps. Performance against national four hour waiting time targets has worsened to the extent that new targets are now being piloted.1 Overall attendance at major emergency departments has grown yearly, reaching 6.2 million patients in 2019.2 In October one in six patients in emergency departments waited more than four hours for assessment or admission, the highest level since the target was introduced in 2004.3 Winter won’t improve things.

Research has shown that many people attending emergency departments could have been assessed and treated appropriately in other settings.4 An excellent example is a …