tbuckley/cabot-search huggingface dataset:
HSR19-099: Harnessing the Voice of Patients With Genetic Mutations in NSCLC Treatment
Authors: Suepattra G. May, Caroline Huber, Alison R. Silverstein, Mark Linthicum, Jason Shafrin, Katie Brown, Upal Basu Roy, Jennifer Bright
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Targeted therapies for non-small lung cancer (NSCLC) have vastly improved survival and other outcomes for patients whose tumors have genetic mutations such as ALK, BRAF, EGFR, and ROS1. Identification of genetic mutations often indicates a mutation-specific course of therapy; however, the relationship between genetic mutation status, patient treatment preferences, and other determinants of patient value in NSCLC cancer care is not well understood. Methods: Qualitative study utilizing focus groups and in-depth interviews were conducted with metastatic NSCLC patients who had received systemic therapy. Interviews explored how patients valued and prioritized factors and attributes associated with NSCLC therapy. Interviews were audio-recorded, transcribed, and coded for key themes using MAXQDA qualitative data analysis software (VERBI, GmbH). Thematic analysis identified determinants of value that patients with genetic mutations considered most important in decision-making. Results: Of 19 total participants with metastatic NSCLC (mean [SD] age, 55.8 [12.6] years; 79% female), 15 (79%) reported a known genetic mutation. Most participants valued oncogene testing and indicated that they had developed a distinct identity based on their specific mutation. Further, participants in our study with identified mutations reported facing distinctly different decisions than those without known mutations. Participants also highlighted unmet needs for diagnosis, treatment, and support tailored to their patient subgroup, including a critical need for better provider training and awareness of genetic testing and mutation-specific treatment options. Across patient subgroups, mutation-specific social media and support networks were highly valued for the care and treatment information they provide, especially among those with rare mutations, limited treatment options, or less-experienced providers. Conclusions: Our study suggests important differences among NSCLC patients based on identified genetic mutations. As treatment for NSCLC evolves, so do the needs and preferences of patients, especially those with driver mutations. Our findings highlight the need for a better understanding of how mutation status may impact patient goals and preferences in order to provide the highest value care to each patient.
Gut bacteria signaling to mitochondria in intestinal inflammation and cancer
Authors: Dakota N. Jackson, Arianne L. Theiss
Journal: Gut Microbes (2019)

The gastrointestinal microbiome plays a pivotal role in physiological homeostasis of the intestine as well as in the pathophysiology of diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Emerging evidence suggests that gut microbiota signal to the mitochondria of mucosal cells, including epithelial cells and immune cells. Gut microbiota signaling to mitochondria has been shown to alter mitochondrial metabolism, activate immune cells, induce inflammasome signaling, and alter epithelial barrier function. Both dysbiosis of the gut microbiota and mitochondrial dysfunction are associated with chronic intestinal inflammation and CRC. This review discusses mitochondrial metabolism of gut mucosal cells, mitochondrial dysfunction, and known gut microbiota-mediated mitochondrial alterations during IBD and CRC.
Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy
Authors: Goele Bosmans, Iris Appeltans, Nathalie Stakenborg, Pedro J. Gomez‐Pinilla, Morgane V. Florens, Javier Aguilera‐Lizarraga, Gianluca Matteoli, Guy E. Boeckxstaens
Journal: Allergy (2019)

Abstract Background The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti‐inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy ( VGX ) and vagus nerve stimulation ( VNS ), on the development and severity of experimental food allergy. Methods Balb/C mice were first sensitized with ovalbumin ( OVA ) in the presence of alum. Prior to oral challenges with OVA , mice were subjected to VGX or VNS . Disease severity was determined by assessing severity and onset of diarrhoea, OVA ‐specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis. Results When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS , on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of α7n AC hR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX 3 CR 1 hi macrophages. Conclusions These results underscore the anti‐inflammatory properties of the vagus nerve and the potential of neuro‐immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune‐mediated diseases.
Helen Salisbury: Dis-integration of cancer care
Authors: Helen Salisbury
Journal: BMJ (2019)

We are lucky enough in our city to have a world class cancer treatment centre. But word is out that the contract for doing combined positron emission tomography and computed tomography scans for the region has been taken away from the local NHS trust and awarded to InHealth, a commercial provider of medical imaging. The contract, along with those for PET-CT imaging at other hospitals across the country, was put out to tender in 2016 by NHS England, and the local hospital’s bid was not chosen.1

There are several …
Randomized Phase 2 Trial of Ofatumumab and Bendamustine Versus Ofatumumab, Bendamustine, and Bortezomib Induction and Maintenance Therapy in Patients (pts) with Previously Untreated High Risk Follicular Lymphoma (FL): Results from CALGB 50904 (Alliance)
Authors: Kristie A. Blum, Sin-Ho Jung, Ian Barak, Eric D. Hsi, Nina D. Wagner-Johnston, Beth Christian, Jim Atkins, Bruce D. Cheson, John P. Leonard, Nancy L. Bartlett
Journal: Blood (2017)
A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF)
Authors: John J.V. McMurray, David L. DeMets, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Anna M. Langkilde, Felipe A. Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjöstrand, Scott D. Solomon
Journal: European Journal of Heart Failure (2019)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.
Trust did not need to suspend proceedings against anaesthetist while police investigated his actions, say judges
Authors: Clare Dyer
Journal: BMJ (2019)

Three appeal court judges have ruled that an NHS trust should have been allowed to go ahead with disciplinary proceedings against a consultant while a police investigation into his conduct was ongoing.1

Andrew Gregg, a consultant anaesthetist, won a High Court injunction in February 2018 barring North West Anglian NHS Foundation Trust from proceeding with its internal disciplinary process before police had finished investigating allegations that he had hastened two patients’ deaths.2 His solicitor had advised him that participating in the trust process could prejudice the criminal investigation.

Police decided in June 2018 to take no action against Gregg, who maintains that his actions were clinically appropriate, and the …
GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells
Authors: Eric L. Smith, Kim Harrington, Mette Staehr, Reed Masakayan, Jon Jones, Thomas J. Long, Khong Y. Ng, Majid Ghoddusi, Terence J. Purdon, Xiuyan Wang, Trevor Do, Minh Thu Pham, Jessica M. Brown, Carlos Fernandez De Larrea, Eric Olson, Elizabeth Peguero, Pei Wang, Hong Liu, Yiyang Xu, Sarah C. Garrett-Thomson, Steven C. Almo, Hans-Guido Wendel, Isabelle Riviere, Cheng Liu, Blythe Sather, Renier J. Brentjens
Journal: Science Translational Medicine (2019)

Early clinical results of chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) appear promising, but relapses associated with residual low-to-negative BCMA-expressing MM cells have been reported, necessitating identification of additional targets. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), normally expressed only in the hair follicle, was previously identified as expressed by mRNA in marrow aspirates from patients with MM, but confirmation of protein expression remained elusive. Using quantitative immunofluorescence, we determined that GPRC5D protein is expressed on CD138+ MM cells from primary marrow samples with a distribution that was similar to, but independent of, BCMA. Panning a human B cell-derived phage display library identified seven GPRC5D-specific single-chain variable fragments (scFvs). Incorporation of these into multiple CAR formats yielded 42 different constructs, which were screened for antigen-specific and antigen-independent (tonic) signaling using a Nur77-based reporter system. Nur77 reporter screen results were confirmed in vivo using a marrow-tropic MM xenograft in mice. CAR T cells incorporating GPRC5D-targeted scFv clone 109 eradicated MM and enabled long-term survival, including in a BCMA antigen escape model. GPRC5D(109) is specific for GPRC5D and resulted in MM cell line and primary MM cytotoxicity, cytokine release, and in vivo activity comparable to anti-BCMA CAR T cells. Murine and cynomolgus cross-reactive CAR T cells did not cause alopecia or other signs of GPRC5D-mediated toxicity in these species. Thus, GPRC5D(109) CAR T cell therapy shows potential for the treatment of advanced MM irrespective of previous BCMA-targeted therapy.
PIP4K2A as a negative regulator of PI3K in PTEN-deficient glioblastoma
Authors: Yong Jae Shin, Jason K. Sa, Yeri Lee, Donggeon Kim, Nakho Chang, Hee Jin Cho, Miseol Son, Michael Y.T. Oh, Kayoung Shin, Jin-Ku Lee, Jiwon Park, Yoon Kyung Jo, Misuk Kim, Patrick J. Paddison, Vinay Tergaonkar, Jeongwu Lee, Do-Hyun Nam
Journal: The Journal of Experimental Medicine (2019)

Glioblastoma (GBM) is the most malignant brain tumor with profound genomic alterations. Tumor suppressor genes regulate multiple signaling networks that restrict cellular proliferation and present barriers to malignant transformation. While bona fide tumor suppressors such as PTEN and TP53 often undergo inactivation due to mutations, there are several genes for which genomic deletion is the primary route for tumor progression. To functionally identify putative tumor suppressors in GBM, we employed in vivo RNAi screening using patient-derived xenograft models. Here, we identified PIP4K2A, whose functional role and clinical relevance remain unexplored in GBM. We discovered that PIP4K2A negatively regulates phosphoinositide 3-kinase (PI3K) signaling via p85/p110 component degradation in PTEN-deficient GBMs and specifically targets p85 for proteasome-mediated degradation. Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. Our results unravel a novel tumor-suppressive role of PIP4K2A for the first time and support the feasibility of combining oncogenomics with in vivo RNAi screen.
A promising approach to identifying health system discrimination and bias
Authors: Ronelle Burger
Journal: The Lancet Global Health (2019)

Madhukar Pai and colleagues' insightful Article1 on gender bias in tuberculosis care in India appears in this issue of The Lancet Global Health. It represents an important contribution to the neglected literature on health worker bias in patient care and case management. This issue matters not only because every patient has the right to care and equal and fair treatment, but also because bias and discrimination affect other shared goals, such as social justice and the effectiveness of health systems.
HSR19-098: Opportunities and Challenges of Managing Breakthrough Cancer Pain (BTCP): An Educational Exercise
Authors: Dean J. Mariano
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Cancer pain is one of the most feared symptoms of cancer and is usually moderate to severe in intensity, particularly in later stages. Opioids are the mainstay maintenance treatment of chronic cancer-related pain. However, between one third and two thirds of cancer patients treated with opioids still experience episodes of severe and debilitating pain known as breakthrough cancer pain (BTCP). Given the number of available treatment approaches for BTCP, healthcare professionals (HCPs) need guidance in selecting the treatment that best meets their patient’s needs and provide the best opportunity for a positive outcome. Aim: Describe the pathophysiology and characteristics of BTCP, its prevalence, and the negative impact on patients. Discuss the characteristics of ideal BTCP treatments and available options. Evaluate the concepts of dependence, addiction, and diversion; ways to minimize risk in cancer patients using opioids; and strategies to address issues. Apply shared decision-making resources to improve collaboration with clinician and patient for optimal BTCP management outcomes by providing best standard of care. Methods: 12 live expert faculty meetings held in oncology/hematology departments in community hospitals, regional cancer centers, and academic centers nationwide from November 17, 2017–June 01, 2018 (Table 1). Target audience of hematologists/oncologists, oncology nurses, physician assistants (PAs), nurse practitioners (NPs), palliative care physicians, pain management specialists, pharmacists, and other HCPs involved in the treatment of patients with BTCP. Results: Overall participation: 321 (anticipated 265; 186 CME completers); 193 oncology MDs; 61 oncology nurses/NP; 17 pharmacists; 22 PAs; 28 other HCPs interested in BTCP. Pre/post-test and 90-day follow-up surveys assessed. 0% commercial bias. Satisfaction of program rated 97%–100%; 96% intend to apply what they acquired to their practice; 97% have a strategy to combat BTCP; 99% are better able to describe BTCP and its negative impact on patients; 98% can better evaluate dependence, addiction, and diversion and to minimize risk of using opioids. +35% average pre- to post-test change with 4 of 5 questions achieving a P ≤.0001 at 90-day follow-up. 72% of participants implemented practice changes by 90-day follow-up. Conclusion: Results suggest that participation in this activity is associated with increased competence and positive practice changes for BTCP.
Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management
Authors: Stephanie A Amiel, Pablo Aschner, Belinda Childs, Philip E Cryer, Bastiaan E de Galan, Brian M Frier, Linda Gonder-Frederick, Simon R Heller, Timothy Jones, Kamlesh Khunti, Lawrence A Leiter, Yingying Luo, Rory J McCrimmon, Ulrik Pedersen-Bjergaard, Elizabeth R Seaquist, Sophia Zoungas
Journal: The Lancet Diabetes & Endocrinology (2019)
Update in Cystic Fibrosis 2018
Authors: Bonnie W. Ramsey, Gregory P. Downey, Christopher H. Goss
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Respiratory Cell and Molecular Biology (AJRCMB), and the Annals of the American Thoracic Society (AnnalsATS) in 2018 to provide readers with an overview of the important contributions to the rapidly evolving literature in the field of cystic fibrosis (CF) published in these three journals.The featured studies focus on advances in five major themes central to the understanding of the pathogenesis and treatment of CF: 1) therapies directed at the underlying defect, 2) early intervention strategies to delay disease progression, 3) respiratory tract infections, 4) inflammation, and 5) epidemiology and outcome measures.Because of word limitations, we regret that not every original contribution could be included.
EPR19-73: Risk of Gastrointestinal and Hepatic Toxicities in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Treated With CDK4/6 Inhibitors
Authors: Anita Sultan, Sriman Swarup, Somedeb Ball, Miguel Quirch, Meily Arevalo, Yin M. Myat, Ye Aung, Myo H. Zaw, Kyaw Z. Thein
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: CDK4 and CDK6 are cyclin-dependent kinases that control transition between G1 and S phases of the cell cycle, hence controlling cell cycle progression by reversible combination with cyclin D1. In cancer cell, CDK4/6 activity is overexpressed, which can lead to amplification or overexpression of the genes encoding for CDK 4/6 or the cyclin D. Additionally, loss of endogenous INK4 inhibitors can also lead to over activity of CDK4 and CDK6. We undertook a meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities associated with CDK 4/6 inhibitors. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018. In our analysis, we incorporated RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: A total of 4,557 patients with advanced breast cancer from 7 phase III and 1 phase II RCTs were eligible. The study arms used were palbociclib/ribociclib/abemaciclib or placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agents. The RR of all-grade side effects were as follows: diarrhea, 1.691 (95% CI: 1.220–2.345; P =.002); nausea, 1.632 (95% CI: 1.447–1.840; P &lt;.001); vomiting, 1.684 (95% CI: 1.256–2.259, P =.001); stomatitis, 2.160 (95% CI: 1.332–3.503; P =.002); elevated AST, 1.832 (95% CI: 1.312–2.558; P &lt;.001); and elevated ALT, 2.150 (95% CI: 1.649–2.803; P &lt;.001). The RR of high-grade side effects were as follows: diarrhea, 2.592 (95% CI: 0.853–7.877; P =.093); nausea, 1.326 (95% CI: 0.589–2.988; P =.496); vomiting, 1.089 (95% CI: 0.479–2.476; P =.839); stomatitis, 2.097 (95% CI: 0.502–0.753; P =.310); elevated AST, 2.274 (95% CI: 1.173–4.410; P =.015); and elevated ALT, 3.988 (95% CI: 2.387–6.663; P &lt;.001). Conclusions: Our study demonstrated that the risk of developing all grade GI toxicities and all grades of hepatic side effects including grade 3 and 4, was high in CDK 4/6 inhibitors group, compared to control arm, and prompt intervention with good supportive care is required.
CLO19-054: Initial Experience of a Newly Set-up Robotic Assisted Radical Prostatectomy Program From a Developing Country—Delineating the Learning Curve
Authors: Shantanu Tyagi, Arandam Roy, Ravimohan Mavuduru, Girdhar Bora, Tushar Aditya Narain, Arup Kumar Mandal
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Historically, the incidence of prostate cancer in India and in nonresident Indians is lower than that in Western populations. Our study aims to assess complications and short-term outcomes of robotic assisted radical prostatectomy (RARP) among postoperative patients from a tertiary care center of a developing country. Materials &amp; Method: Prospective cohort/next 50 group, surgery between July 2017 to September 2018: Preoperative variables included demographic profile, MRI findings, PSA values, prostate biopsy reports including the Gleason score, erectile function assessment using the IIEF-5 questionnaire. Intraoperative variables included duration of surgery, blood loss, status of neurovascular bundles, whether could be preserved, lymph node dissection, and its extent. Postoperative variables included complications following the surgery (Clavien-Dindo classification), hospital stay, time of indwelling catheter. Follow-up data included serum PSA levels, status of urinary continence (daily urinary pad log ), and sexual function (IIEF 5 scores) at 3 months from surgery, then every 3 months. Retrospective cohort/first 50, surgery between December 2014 to 30th June 2017: Preoperative, intraoperative, and postoperative variables were recorded like in prospective cohort and were followed prospectively during study period. Results: Preoperative variables were comparable between two groups (Tables 1–3).Operative duration was significantly better in “next 50” group (mean, 236 minutes; range, 100–450 minutes) as compared to “first 50” group (mean, 350 minutes; range, 178–560 minutes, Duration of hospital stay is significantly less in “next 50” group (mean, 2.6 vs 4.5 days). Postoperative complications were also less commonly noted in “next 50” group (5% vs 14%; Table 4). Comparative postoperative erectile dysfunction rates were significantly less in “next 50” group (6% vs 36%), and though the postoperative incontinence rates were less in “next 50” group, it was found to be statistically insignificant (Table 5). Conclusion: Robotic-assisted radical prostatectomy is a safe and feasible option for the treatment of clinically localized prostate cancer. After due course of training period favorable and promising results can be replicated at a newly set robotic program.
Incentive hope: A default psychological response to multiple forms of uncertainty
Authors: Patrick Anselme, Onur Güntürkün
Journal: Behavioral and Brain Sciences (2019)

Abstract Our target article proposes that a new concept – incentive hope – is necessary in the behavioral sciences to explain animal foraging under harsh environmental conditions. Incentive hope refers to a specific motivational mechanism in the brain – considered only in mammals and birds. But it can also be understood at a functional level, as an adaptive behavioral strategy that contributes to improve survival. Thus, this concept is an attempt to bridge across different research fields such as behavioral psychology, reward neuroscience, and behavioral ecology. Many commentaries suggest that incentive hope even could help understand phenomena beyond these research fields, including food wasting and food sharing, mental energy conservation, diverse psychopathologies, irrational decisions in invertebrates, and some aspects of evolution by means of sexual selection. We are favorable to such extensions because incentive hope denotes an unconscious process capable of working against many forms of adversity; organisms do not need to hope as a subjective feeling, but to behave as if they had this feeling. In our response, we carefully discuss each suggestion and criticism and reiterate the importance of having a theory accounting for motivation under reward uncertainty.
Abstract 14978: Quality Indicators for the Cardiovascular Intensive Care Unit: Systematic Review and Directors Survey
Authors: Michael Goldfarb, Lior Bibas, L. Kristin Newby, Timothy D Henry, Jason Katz, Sean van Diepen, Bojan Cercek
Journal: Circulation (2017)

Background: Quality indicators (QIs) are increasingly used in cardiovascular care as measures of performance but there is currently no consensus on indicators for the cardiovascular intensive care ...