tbuckley/cabot-search huggingface dataset:
Anxiety, depression, pain, and social support in a large representative cancer population.
Authors: Sarah Kathryn Galloway, Patrick Meadors, Danielle Boselli, Declan Walsh
Journal: Journal of Clinical Oncology (2019)

76 Background: Pain is one of the most common cancer symptoms. Individuals in pain often experience psychological distress in the form of anxiety and depression. Social support is an important resource utilized by patients to cope with cancer. Aims: (1) Identify clinicodemographic factors influencing cancer pain; (2) examine social support as a moderator of the relation between anxiety, depression and cancer pain. Methods: Participants included stage I-IV cancer patients (N = 11,815) who completed a routine tablet-based psychosocial distress screening at a large academic hybrid, multi-site, community-based cancer institute (Jan 2017- Jan 2019). Participants were matched to the Cancer Registry (N = 7,333); clinicodemographic factors were incorporated into lasso regression models. Models identified pain predictors from self-reported anxiety, depression and social support. Analyses examined if the effect of anxiety and depression on pain differed by levels of social support. Results: Median age was 59 (RNG, 18-101), 61% female and 77% white. Tumor site (GI, Gyn, head/neck), advanced disease, black race, and lower income were independently associated with severe pain. Anxiety (β = 0.48, p &lt; .001) and depression (β = 0.69, p &lt; 0.001) were related to pain intensity after accounting for clinicodemographic factors. The effect of depression on pain differed by level of social support (p = 0.009). The effect of anxiety on pain differed in patients reporting transportation issues (p = 0.035). Conclusions: This is the largest study to date examining cancer pain intensity, psychological factors of anxiety and depression, and social support. Our data suggests that patient characteristics of race, income, tumor site, and disease staging independently predict pain intensity. Anxiety and depression are significant factors of pain intensity; these associations remain after accounting for patient characteristics. Social support buffers the negative impact of anxiety/depression on pain. Clinicians who treat cancer pain should be attuned to modifiable psychological factors which can greatly influence a patient’s pain experience. Findings emphasize the need for interdisciplinary multimodal approaches for cancer pain.
Tumour mutation burden analysis in a 5660-cancer-patient cohort reveals cancer type-specific mechanisms for high mutation burden
Authors: Y.-S. Zang, X.-D. Jiao, X.-C. Zhang, B. Qin, D. Liu, L. Liu, J. Ni, Z. Ning, L. Chen, L. Zhu, S. Qin, J. Zhou, S. Ying, X. Chen, A. Li, T. Hou, A. Lizaso, H.-H. Zhang, K. Liu, Z. Wang
Journal: Annals of Oncology (2019)
Investigating cortisol excess or deficiency: a practical approach
Authors: Fahmy W F Hanna, Basil G Issa, Brian Kevil, Anthony A Fryer
Journal: BMJ (2019)

### What you need to know

A 67 year old woman with no significant medical history required urgent orthopaedic surgery after a fall. In preparation, her bloods were collected and a random cortisol was requested, which came back at 763 nmol/L. She did not have diabetes or hypertension. The anaesthetist reviewed and commented: “High cortisol, not safe for surgery until further evaluation.” 

A 24 year old man with previously well controlled type 1 diabetes presented with repeated hypoglycaemic episodes. Serum cortisol in clinic at 9 am came back as 143 nmol/L. 

Cortisol, secreted by the adrenal cortex, regulates blood pressure, glucose metabolism, and physiological responses to stress. Both cortisol over-secretion (hypercortisolism, Cushing’s syndrome) and under-secretion (hypocortisolism such as in Addison’s disease) are uncommon: the prevalence of Addison’s disease is 6-9 per 100 000,1 while that of Cushing’s syndrome is 4/100 000.2 However, given the potential for life threatening consequences (such as in acute adrenal crisis) and the range of associated non-specific symptoms, it is critical for clinicians to understand how to interpret and manage cortisol status. Cortisol excess could be due to an adrenal cortisol-secreting tumour or to a functional pituitary tumour (Cushing’s disease), or, less commonly, malignant tumours can …
SLC20A1 at the Interface between Macrophages and Red Blood Cells
Authors: Federica Quattrone, Riem Gawish, Rui Martins, Anna-Dorothea Gorki, Martin Watzenboeck, Anastasiya Hladik, Karin Lakovits, Manuele Rebsamen, Enrico Girardi, Giulio Superti-Furga, Sylvia Knapp
Journal: Blood (2019)
Combination effects of nobiletin with CDDP on gastric cancer cells
Authors: Nobunari Yoshimizu, Yoshihide Otani, Yoshiro Saikawa, Tsunehiro Takahashi, Masashi Yoshida, Toshiharu Furukawa, Tetsuro Kubota, Koichiro Kumai, Toshiki Tomita, Kaori Kameyama, Yasunori Okada, Akira Ito, Masaki Kitajima
Journal: Cancer Research (2004)

838  Flavonoids are polyphenolic compounds found in various foods of plant origin. Over 4000 flavonoids have been discovered and categorized according to structural class, hydroxylation pattern, other substitutions, degree of polymerization, and conjugation. Epidemiological studies indicate that flavonoid ingestion is associated with a reduced risk of certain forms of cancer and chronic disease. Recently, citrus flavonoids including nobiletin, found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, are known to suppress MMPs production and exert anticancer activity in vitro. We have already reported the suppression of peritoneal nodules formation of gastric cancer cells in peritoneal dissemination model of SCID mouse (Jpan J Cancer Res, 92:1322-1328, 2001). We next investigate the anti-tumor effects and the combination effect of nobiletin and CDDP on gastric cancer cells.   Human gastric cancer cell lines, TMK-1, MKN-45, MKN-74 and KATO-III and mouse fibroblast cell, clone A-31were used for this study. The direct cytotoxicity of nobiletin was examined by MTT assay and the effect on cell cycle was measured by DNA histogram using flow cytometry. On the basis of the data obtained we then evaluated the combined effect on gastric cancer of nobiletin with a conventional anti-cancer drug, CDDP. Nobiletin significantly showed the direct cytotoxicity on four cell lines examined in a concentration-dependent manner. In contrast, nobiletin had no significant direct cytotoxicity on Clone A-31. Apoptosis was observed and the block of cell cycle was evident at G1 phase by nobiletin. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control. Our results suggest that nobiletin may represent one component of a new treatment protocol for the suppression of gastric cancer, with less side-effects over existing therapy. Much investigation of dosage remains to be done, however, the present study suggests a promising new model for clinical investigation of advanced gastric cancer.
Racial disparities in end-of-life care among Louisiana cancer decedents in a population-based study from 2011-2017.
Authors: Laura M Perry, Leah E. Walsh, Ronald Horswell, Lucio Miele, San Chu, Brian Melancon, John Lefante, Christopher M. Blais, Michael Hoerger
Journal: Journal of Clinical Oncology (2019)

46 Background: Cancer patients’ comfort near the end of life is often undermined by unnecessary aggressive treatments. Furthermore, Black adults receive more aggressive end of life care compared to White adults. We hypothesized that these inequalities would be especially pronounced in Louisiana given regional trends of high cancer mortality coupled with inaccessibility to high quality cancer care. Methods: This was a retrospective analysis of end-of-life care using a Patient-Centered Outcomes Research Institute (PCORI)-funded PCORnet database in the Deep South, called Research Action for Health Network (REACHnet). Of 3,089,092 individuals included, 1,290 met eligibility criteria for the present study: 1) died in Louisiana with a metastatic cancer diagnosis between January 1, 2011 and December 31, 2017, 2) had at least one outpatient clinic visit within six months of death, and 3) self-identified as White or Black. In collaboration with the Louisiana Clinical and Translational Science (LA CaTS) Center, we extracted data on five validated indicators of aggressive care in the final 30 days of life: chemotherapy use, inpatient hospitalizations, ED admissions, ICU admissions, and mechanical ventilation. Hypotheses were analyzed using binary logistic regression to examine whether patient race (White vs. Black) was associated with receipt of each indicator of aggressive end-of-life care, while controlling for sex, age, number of comorbidities, and cancer type. Results: Patients were either White ( n = 875, 67.8%) or Black ( n = 415, 32.2%) adults, and the majority were ≥60 years old (72.4%). Most patients (85.0%) received at least one indicator of aggressive care in the last 30 days of life ( M = 1.91, SD = 1.23), most commonly inpatient hospitalizations (77.0%). Black individuals were more likely than White individuals to be hospitalized ( OR = 1.66, 95% CI: 1.21 to 2.27, p= .002) or admitted to the ED ( OR= 1.57, 95% CI: 1.16 to 2.13, p= .004) during their last month of life, but race was not associated with other indicators. Conclusions: Findings have implications for informing healthcare decision making near the end of life for patients, families, and clinicians in the Deep South.
A Verdict for Glimepiride: Effective and Not Guilty of Cardiovascular Harm
Authors: Matthew C. Riddle
Journal: Diabetes Care (2019)

Amazingly, whether sulfonylureas pose unacceptable risks compared with other treatments for diabetes has been debated for nearly 50 years. Ever since increased mortality was associated with tolbutamide in the University Group Diabetes Program (UGDP) (1), a warning of potential cardiovascular risk for drugs in this class has been mandated. Their tendency to cause both nonsevere and severe hypoglycemia worries patients and providers alike, who fear that hypoglycemia may precipitate serious cardiovascular events. Despite these concerns, sulfonylureas continue to be widely used for type 2 diabetes because they reliably improve glycemic control, lack symptomatic side effects other than hypoglycemia, and are very inexpensive. A recent commentary in Diabetes Care questioned whether the modern drugs in this class—glimepiride and gliclazide—deserve the shadow of guilt cast over them by studies of older sulfonylureas (2). They are conveniently dosed once daily and are less likely to cause hypoglycemia than the older agents, especially glyburide (also called glibenclamide). Unlike glyburide, they do not oppose ischemic preconditioning, a cardioprotective mechanism (3), and meta-analytic evidence suggests they are associated with lower rates of cardiovascular events than glyburide (4).

Up to now, high-quality evidence to resolve the risk-versus-benefit debate has been lacking. Epidemiologic analyses of clinical databases and meta-analyses of short-term clinical studies comparing a sulfonylurea with placebo or an active comparator have shown conflicting results (5–8). Some studies comparing sulfonylureas with metformin suggest higher cardiovascular risk with sulfonylureas (9), but it is unclear whether this is because sulfonylureas are harmful or metformin is protective. Experience in the UK Prospective Diabetes Study (UKPDS) favors the latter interpretation. Over 10 years of randomized comparison with a conventional lifestyle-based regimen in the UKPDS, basal insulin or a sulfonylurea did not alter cardiovascular outcomes, whereas metformin reduced cardiovascular and all-cause mortality (10). But because metformin is preferred as …
Co-production of a research and advocacy agenda for Inclusion Health
Authors: Serena Luchenski, Chantal Edge, Niccola Hutchinson-Pascal, Binta Sultan, Georgia Black, Stan Burridge, Luke Johnson, Natasha Palipane, Diana Margot Rosenthal, Cassandra Fairhead, Emma King, Dan Lewer, Velvet Dibley, Zana Khan, Lucie Collinson, Neha Pathak, Alistair Story, Andrew Hayward
Journal: The Lancet (2019)
Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study
Authors: Katri Lindfors, Jake Lin, Hye-Seung Lee, Heikki Hyöty, Matti Nykter, Kalle Kurppa, Edwin Liu, Sibylle Koletzko, Marian Rewers, William Hagopian, Jorma Toppari, Annette-Gabriele Ziegler, Beena Akolkar, Jeffrey P Krischer, Joseph F Petrosino, Richard E Lloyd, Daniel Agardh
Journal: Gut (2019)

Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children.
Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?
Authors: Andrew B. Nixon, Kurt A. Schalper, Ira Jacobs, Shobha Potluri, I-Ming Wang, Catherine Fleener
Journal: Journal for ImmunoTherapy of Cancer (2019)

The immunologic landscape of the host and tumor play key roles in determining how patients will benefit from immunotherapy, and a better understanding of these factors could help inform how well a tumor responds to treatment. Recent advances in immunotherapy and in our understanding of the immune system have revolutionized the treatment landscape for many advanced cancers. Notably, the use of immune checkpoint inhibitors has demonstrated durable responses in various malignancies. However, the response to such treatments is variable and currently unpredictable, the availability of predictive biomarkers is limited, and a substantial proportion of patients do not respond to immune checkpoint therapy. Identification and investigation of potential biomarkers that may predict sensitivity to immunotherapy is an area of active research. It is envisaged that a deeper understanding of immunity will aid in harnessing the full potential of immunotherapy, and allow appropriate patients to receive the most appropriate treatments. In addition to the identification of new biomarkers, the platforms and assays required to accurately and reproducibly measure biomarkers play a key role in ensuring consistency of measurement both within and between patients. In this review we discuss the current knowledge in the area of peripheral immune-based biomarkers, drawing information from the results of recent clinical studies of a number of different immunotherapy modalities in the treatment of cancer, including checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T cells, and anti-cancer vaccines. We also discuss the various technologies and approaches used in detecting and measuring circulatory biomarkers and the ongoing need for harmonization.
Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
Authors: Meagan B. Ryan, Ferran Fece de la Cruz, Sarah Phat, David T. Myers, Edmond Wong, Heather A. Shahzade, Catriona B. Hong, Ryan B. Corcoran
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Although KRAS represents the most commonly mutated oncogene, it has long been considered an “undruggable” target. Novel covalent inhibitors selective for the KRASG12C mutation offer the unprecedented opportunity to target KRAS directly. However, prior efforts to target the RAS–MAPK pathway have been hampered by adaptive feedback, which drives pathway reactivation and resistance. Experimental Design: A panel of KRASG12C cell lines were treated with the KRASG12C inhibitors ARS-1620 and AMG 510 to assess effects on signaling and viability. Isoform-specific pulldown of activated GTP-bound RAS was performed to evaluate effects on the activity of specific RAS isoforms over time following treatment. RTK inhibitors, SHP2 inhibitors, and MEK/ERK inhibitors were assessed in combination with KRASG12C inhibitors in vitro and in vivo as potential strategies to overcome resistance and enhance efficacy. Results: We observed rapid adaptive RAS pathway feedback reactivation following KRASG12C inhibition in the majority of KRASG12C models, driven by RTK-mediated activation of wild-type RAS, which cannot be inhibited by G12C-specific inhibitors. Importantly, multiple RTKs can mediate feedback, with no single RTK appearing critical across all KRASG12C models. However, coinhibition of SHP2, which mediates signaling from multiple RTKs to RAS, abrogated feedback reactivation more universally, and combined KRASG12C/SHP2 inhibition drove sustained RAS pathway suppression and improved efficacy in vitro and in vivo. Conclusions: These data identify feedback reactivation of wild-type RAS as a key mechanism of adaptive resistance to KRASG12C inhibitors and highlight the potential importance of vertical inhibition strategies to enhance the clinical efficacy of KRASG12C inhibitors. See related commentary by Yaeger and Solit, p. 1538
SAT0139 A controlled long-term treatment of fibromyalgia patients with sertraline
Authors: P Sarzi-Puttini, R Pettorossi, A Baffigi, M Cazzola, T Fiorini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The pathophysiology of Fibromyalgia syndrome (FM) is mostly uncertain and the conventional medication therapy results from empirical research. FM is a common disorder that is estimated to affect 2–4% of the population. Serotonin reuptake inhibitors are now used in FM due to their interference in the serotonin metabolism. <h3>Objectives</h3> To evaluate the relative efficacy and tolerability of Sertraline in the long-term treatment of fibromyalgia patients. <h3>Methods</h3> Fifty patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered in a 6-month prospective, controlled trial; all patients were treated with Sertraline (50–100 mg/day). Symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or analgesic was allowed at optimal doses that were established on the basis of each patient?s needs. Five control examinations were planned (at baseline, after 15 days at month 1,2,3, and 6). Primary efficacy measures were (1) patient self assessment of pain on a 10 cm visual analogue scale (VAS), (2) tender point index (TPI) which is the sum of individual tenderness severity at each of the 18 standard ACR tender points and (3) Fibromyalgia Impact Questionnaire (FIQ). Other six secondary clinical efficacy measures were selected: physician and patients' global assessment of the disease, sleep quality assessment using a 100-mm visual analogue scale, Health Assessment Questionnaire (HAQ) the Hamilton rating scale for depression (HRSD) and the Hamilton rating scale for anxiety (HRSA). Tolerability assessment was based on the occurrence of any adverse events. <h3>Results</h3> All primary efficacy measures were significantly improved after 1 month of treatment (p &lt; 0.05) and maintained a significant improvement throughout the study. No further improvement was however observed after 3 months of treatment. Most of the secondary efficacy measures improved significantly; in particular HRDS and HRSA (p &lt; 0.01) improved after 1 month of treatment. After 6 months of treatment, 23 patients (45%) were still on treatment with Sertraline. Most of the withdrawals were due either to inefficacy (12 patients), side-effects (7 patients) or lost to follow-up (8 patients). <h3>Conclusion</h3> Our data confirm the long-term efficacy of sertraline in a discrete percentage of patients with fibromyalgia.
Sexual violence against women: a multidisciplinary integrated care model
Authors: Giussy Barbara, Federica Facchin, Paolo Vercellini, Cristina Cattaneo, Alessandra Kustermann
Journal: BMJ (2019)

Ades and colleagues say that women who have experienced sexual violence require multidisciplinary, trauma informed care tackling their medical and psychological needs, either short or long term.1 Our sexual and domestic violence service, founded in 1996, adopts an integrated multidisciplinary approach, with a team composed of gynaecologists, psychologists, social workers, forensic practitioners, …
Therapy of Paediatric B-ALL with a Fast Off Rate CD19 CAR Leads to Enhanced Expansion and Prolonged CAR T Cell Persistence in Patients with Low Bone Marrow Tumour Burden, and Is Associated with a Favourable Toxicity Profile
Authors: Sara Ghorashian, Anne Marijn Kramer, Shimobi Onuoha, Gary Wright, Jack Luke Bartram, Rachel Richardson, Sarah J Albon, Joan Casanovas Company, Fernanda Castro, Bilyana Popova, Krystal Villanueva, Jenny Yeung, Aleks Guvenel, Patrycja Wawrzyniecka, Danielle Pinner, Jan Chu, Giovanna Lucchini, Juliana Silva, Oana Ciocarlie, Arina Lazareva, Sarah Inglott, Kimberly Gilmour, Gulrukh Ahsan, Kim Champion, Andre Lopes, Allan Hackshaw, Farzin Farzaneh, Robert Chiesa, Kanchan Rao, Denise Bonney, Sujith Samarasinghe, Nicholas John Goulden, Ajay Vora, Paul Veys, Rachael E Hough, Robert Wynn, Martin Pule, Persis J Amrolia
Journal: Blood (2019)
Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
Authors: M. Miki, S. Takao, M. Konishi, Y. Shigeoka, M. Miyashita, H. Suwa, M. Imamura, T. Okuno, K. Hirokaga, Y. Miyoshi, K. Murase, A. Yanai, K. Yamagami, K. Akazawa
Journal: Annals of Oncology (2019)
OCM community oncology palliative care program: Sites of patient care in last 180 days before hospice or death by cancer types.
Authors: Adil Jamal Akhtar, Karna Sheth, Jeffrey H. Margolis, Karma Maxwell, Tammy Scott-Barney, Andrew A. Muskovitz, George Howard, Richard Philip Zekman, Yusuf Qamruzzaman, Samer Ballouz, Lexi Stortz, Maria Fabbiano, Mitchell Folbe, Mohammed Ibrahim
Journal: Journal of Clinical Oncology (2019)

69 Background: Michigan Health Professionals (MHP) participates in Oncology Care Model (OCM). A community oncology program for early and timely involvement of palliative care (PC) was launched in 2017 to achieve OCM goals of high quality, cost-effective, coordinated care. Previously, we showed that early enrollment in PC increased hospice utilization, decreased hospitalization and outpatient facility cost in last 30-days of death or end of OCM episode. PC improved quality of care in OCM patients. This study aims to see the effect of PC by patient care setting in the last 180-days before hospice or death. Methods: Retrospective claims review was performed with PC patients referred from September 2017 – December 2018. Last 180-days was defined by the entry into hospice, patient death, or OCM claim limit (12/31/2018), whichever was first to occur. OCM claims were analyzed by Integra Connect. Patient care setting utilization, in days (LOS), was identified for FACILITY: inpatient, skilled nursing, outpatient facility (ER, observation, etc.), physician office, and HOME HEALTH: home health agency visits. When no claim was found within the last 180-days, the patient was assumed to be at home or with no-care (HOME). Results: PC-Engaged patients had lower LOS in FACILITY + HOME HEALTH care settings and more days at HOME vs PC declined or unable to reach (average difference of 14 days). PC-Engaged patients had lower LOS in FACILITY + HOME HEALTH vs. matched PC-not referred patients who died or entered hospice (average difference of 26 days). In lung cancer, PC-Engaged patients had lower LOS in FACILITY + HOME HEALTH vs. PC declined or unable to reach (average difference of 27 days). In pancreatic cancer, PC-Engaged patients had lower LOS in FACILITY + HOME HEALTH vs. PC declined or unable to reach (average difference of 17 days). Conclusions: Patients who are PC-Engaged spent more time at home and less time in facilities over the last 6 months before end-of-life. Patients who were referred to PC with advanced lung and pancreatic cancer showed the most opportunity for impact with PC engagement. Study was limited by OCM claims available as of June 2019. Results may be refreshed as more data becomes available.