tbuckley/cabot-search huggingface dataset:
RNA N6‐methyladenosine methyltransferase‐like 3 promotes liver cancer progression through YTHDF2‐dependent posttranscriptional silencing of SOCS2
Authors: Mengnuo Chen, Lai Wei, Cheuk‐Ting Law, Felice Ho‐Ching Tsang, Jialing Shen, Carol Lai‐Hung Cheng, Long‐Hin Tsang, Daniel Wai‐Hung Ho, David Kung‐Chun Chiu, Joyce Man‐Fong Lee, Carmen Chak‐Lui Wong, Irene Oi‐Lin Ng, Chun‐Ming Wong
Journal: Hepatology (2017)

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have predominantly focused on DNA methylation, histone modifications, and chromatin remodeling. Recently, diverse and reversible chemical modifications of RNAs have emerged as a new layer of epigenetic regulation. N6‐methyladenosine (m6A) is the most abundant chemical modification of eukaryotic messenger RNA (mRNA) and is important for the regulation of mRNA stability, splicing, and translation. Using transcriptome sequencing, we discovered that methyltransferase‐like 3 (METTL3), a major RNA N6‐adenosine methyltransferase, was significantly up‐regulated in human hepatocellular carcinoma (HCC) and multiple solid tumors. Clinically, overexpression of METTL3 is associated with poor prognosis of patients with HCC. Functionally, we proved that knockdown of METTL3 drastically reduced HCC cell proliferation, migration, and colony formation in vitro . Knockout of METTL3 remarkably suppressed HCC tumorigenicity and lung metastasis in vivo . On the other hand, using the CRISPR/dCas9‐VP64 activation system, we demonstrated that overexpression of METTL3 significantly promoted HCC growth both in vitro and in vivo . Through transcriptome sequencing, m6A sequencing, and m6A methylated RNA immuno‐precipitation quantitative reverse‐transcription polymerase chain reaction, we identified suppressor of cytokine signaling 2 (SOCS2) as a target of METTL3‐mediated m6A modification. Knockdown of METTL3 substantially abolished SOCS2 mRNA m6A modification and augmented SOCS2 mRNA expression. We also showed that m6A‐mediated SOCS2 mRNA degradation relied on the m6A reader protein YTHDF2‐dependent pathway. Conclusion : METTL3 is frequently up‐regulated in human HCC and contributes to HCC progression. METTL3 represses SOCS2 expression in HCC through an m6A‐YTHDF2‐dependent mechanism. Our findings suggest an important mechanism of epigenetic alteration in liver carcinogenesis. (H epatology 2018;67:2254‐2270).
Inflammation, age and changing microbiology: the search for causation in the cystic fibrosis airways
Authors: Geraint B. Rogers
Journal: European Respiratory Journal (2017)

Since the first reports of bacterial lung infections in patients with cystic fibrosis (CF) almost 80 years ago, concerted efforts have been made to identify the microbes responsible and to determine their contribution to lung disease. However, while CF respiratory microbiology has helped to shape clinical practice, our understanding of the relationships between microbial colonisation of the lung, inflammation and disease remains relatively poor. A survey of CF BALF reports lung microbiota to vary with age and inflammation but causality remains hard to pin down <http://ow.ly/hEjX30fVMoL>
Hospitalization costs for nausea and vomiting: A savings opportunity.
Authors: Eric Roeland, Joseph Ma, Gary Binder, Robert Goldberg, Robert Paglia, Russell L. Knoth, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2017)

155 Background: Nausea and vomiting (NV) are tracked by CMS as 2 of 10 top drivers of potentially avoidable hospital admissions for patients with cancer. These admissions pose a savings opportunity, yet limited literature exists on the costs of chemotherapy-induced NV (CINV). Burke’s 2010 assessment of 19,139 patients from 2004-2007 found CINV hospitalizations cost $7,448 and comprised the majority of overall CINV events and costs vs ambulatory events. Rashid (2016) evaluated 1,682 patients with metastatic breast cancer from 2007-2011 and found CINV admissions cost $10,074 in 2013 US dollars. Using data from the US Agency for Healthcare Research and Quality ’s Healthcare Cost and Utilization Project website (HCUPnet), and after applying adjustment factors from recent literature, we evaluated the cost of NV hospitalizations. Methods: Data on US hospital discharges for NV (based on primary discharge diagnosis) were obtained for 2014 from HCUPnet. Charges were adjusted using Smith’s (2015) model showing commercial insurers paid 48.7% of their hospital charges. They were further modified to include professional fees equaling 26.4% of facilities paid amounts, as reported by Peterson (2015). The CPI-Medical rate was used to adjust costs to 2016 dollars. A US payer perspective was used. The proportion of total NV discharges due to CINV is not known; it is also unknown whether charges for CINV differ from those for NV overall. Results: HCUPnet reported 37,730 hospital discharges for NV, with mean charges of $23,603 per event. The mean payment to hospitals, after adjustment to reflect amounts insurers actually paid, was estimated at $11,232 per event. Adding physicians’ professional fees incurred in the hospital setting yet normally charged separately yielded a total hospitalization cost of $14,197 ($15,120 in 2016 US dollars). Conclusions: Hospitalization for NV is common and costly; adjusted paid amounts averaged &gt; $15,000 per discharge, a level consistent with the CINV literature. This economic impact, in addition to the consequences for patients’ quality of life, suggests the need for continued advances in preventing CINV and optimizing compliance with national antiemetic guidelines, particularly for chemotherapy with high emetogenic potential.
Successful integration of palliative care services into the multidisciplinary multiple myeloma clinics: An observational study based on a single institution experience.
Authors: Neil Nagovski, Amanda Brahim, Patrick Taylor Reynolds, Marco Ruiz
Journal: Journal of Clinical Oncology (2017)

142 Background: The pain syndromes, both acute and chronic are prevalent and often the only complaints affecting the patients’ quality of life and functional capacity. Here we describe our experience of successful integration of palliative care service into multiple myeloma (MM) management in a form of the disease specific multidisciplinary clinic. Methods: We have established a dedicated monthly multidisciplinary clinic for all patients diagnosed with symptomatic MM as a pilot project to incorporate different specialties involved in MM care with the goal to improve on disease management, increase compliance with office visits, reduce emergency department visits and benefit a healthcare system. Patients were able to have the same day visits with medical oncologist, radiation oncologists, palliative care physician, integrative medicine and medical psychologist. Over the course of two years (April 2015 through March 2017), we provided care to 39 unique MM patient. Results: After medical/transplant oncology encounters (N = 601), the most encountered specialists were palliative care (N = 208), followed by radiation oncology (N = 34) and integrative medicine/medical psychology (N = 33). The rate of missed office visits for multidisciplinary clinic was 5%, compared to average 7% for all cancer patients at our center. The rates of emergency department visits were rising in proportion to non-compliance with multidisciplinary clinic visits (correlation coefficient 0.43) Conclusions: Patients with MM cared for at the multidisciplinary clinic had better compliance with office visits and fewer unplanned emergency department visits in comparison patients with other oncologic disorders. The rates of emergency departmentvisits were proportional to non-compliance with multidisciplinary clinic visits. The degree of utilization of integrative medicine and psychology was comparable to radiation oncology encounters suggesting that psychological, behavioral, dietary interventions, complementary, physical therapies and rehabilitation have an important and growing role in MM management.
Risk of health-related quality of life events from pain and fatigue among patients with hormone receptor-positive HER-2 negative metastatic breast cancer treated with CDK 4/6 inhibitor.
Authors: Myat M. Han, Kyaw Zin Thein, Myo Zaw, Aung Tun, Paul D'Cunha, Fred L. Hardwicke, Catherine Jones
Journal: Journal of Clinical Oncology (2017)

215 Background: Molecular heterogeneity in breast cancer has led to increasing attention in the role of cell cycle signaling especially the cyclins and their associated proteins, cycle-dependent kinases (CDK), in carcinogenesis and treatment resistance in hormone receptor-positive metastatic breast cancer. Many CDK 4/6 agents have been proven beneficial. Nevertheless, health-related quality of life from pain and fatigue remains a concern. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine these risks. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention back pain, pain in arms and legs, arthralgia and fatigue as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: A total of 2671 patients with hormone receptor-positive HER2-negative metastatic breast cancer from four phase 3 studies and one phase 2 study were eligible for analysis. The study arms used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arms utilized placebo in combination with letrozole or fulvestrant. The relative risk (RR) of all-grade back pain was 0.97 (95% CI: 0.81- 1.16; p = 0.76); all-grade pain in arms and legs was 0.98 (95% CI: 0.74- 1.30; p = 0.90); all-grade arthralgia was 0.98 (95% CI: 0.75- 1.27; p = 0.88); and all-grade fatigue was 1.35 (95% CI: 1.20- 1.52; p &lt; 0.0001). The RR of high-grade back pain was 1.47 (95% CI: 0.51- 4.23; p = 0.46); high-grade pain in arms and legs was 0.12 (95% CI: 0.02- 0.73; p = 0.02); high-grade arthralgia was 1.14 (95% CI: 0.40- 3.26; p = 0.79); and high-grade fatigue was 3.06 (95% CI: 1.41- 6.61; p = 0.004). Conclusions: Patients on CDK4/6 inhibitor-based regimens experienced a significant increase in all-grades of fatigue with a relative risk of 3.06 for grade 3 and 4 fatigue whereas they noted a decrease in high-grade pain in the arms and legs favoring CDK 4/6 inhibitor based regimens.
Spirituality among Latino caregivers of patients with advanced cancer: A qualitative study.
Authors: Marvin Omar Delgado-Guay, Susana McCollom, Alejandra Palma, Eva Rossina Duarte, Monica Grez, Laura Tupper, Eduardo Bruera
Journal: Journal of Clinical Oncology (2017)

180 Background: Caregivers of cancer patients often face significant physical, social, and emotional distress. There has been limited research on the association between Latino Caregivers’ spirituality/religiosity, meaning, and spiritual pain. Methods: We interviewed 336 Latino Caregivers of patients at Palliative Care clinics in Chile, Guatemala, and the US. Five open-ended questions were asked about spirituality, religion, meaning, and spiritual pain. Answers were transcribed and data analyzed. The analytic framework was based on an interpretive phenomenological analysis. Initial themes were grouped into themes, connections between themes were developed until a thematic rationale was achieved. Results: Latino caregivers’spirituality and religious beliefs were described as an anchor during the painful witnessing of a loved-ones’suffering. Main themes emerged about relationships, inner strength, hope, and acceptance/reconciliation. It was reported as an integrative force to help them to cultivate hope and love walking through their love one’s illness and their journey as caregivers. They expressed meaning as a manifestation of spirituality together with their love to others(spouse, family, others). The presence of Spiritual Pain was common and manifested as suffering and potential loss of loved ones, and broken relationship with Higher Power, that triggered a profound experience of their own pain(both spiritual and emotional) and their own quality of life. This was expressed in physical terms such as “heartache” and “soul ache.” Through discernment, prayer, and relationships with loved-ones, spirituality was integrated as a healing force during the caregiver journey. Spirituality was reported as a substance of hope weaved into an integrative process, as caregivers reconciled the tension of faith with sorrow. Conclusions: Spirituality and religious beliefs are reported as fundamental for Latino Caregivers. Despite these elements, Spiritual Pain is common and affects all aspects of their humanity. Most of them experienced a reconciliation experience with the broken relationships with themselves, with others or with Higher Power.
Rising incidence of heart failure demands action
Authors: Faiez Zannad
Journal: The Lancet (2017)

Heart failure is a life-threatening syndrome with substantial morbidity and mortality and is a burden to patients, their carers, and health systems. Estimates of heart failure incidence and prevalence are difficult to generate. Accurate epidemiological estimates of heart failure, however, are crucial to ensure resources are appropriately and adequately allocated to treat patients with existing disease, and to inform prevention methods among those at risk.
Risk of ovarian function recovery should be considered when switching from treatment with adjuvant tamoxifen to aromatase inhibitor therapy in women with chemotherapy‐induced amenorrhea
Authors: Clement Chung
Journal: CA A Cancer Journal for Clinicians (2017)

Key Points In this study, the risk of a return to menses and/or premenopausal estradiol/follicle‐stimulating hormone levels by 30 months after a switch from adjuvant tamoxifen to aromatase inhibitor therapy in women with postmenopausal estradiol levels at the time of the switch was 15.2% (38 of 250 patients) for women who had chemotherapy‐induced amenorrhea and were aged younger than 50 years at the time of breast cancer diagnosis. The risk was 1.2% (1 in 79 women) for women who were aged 50 to 54 years but still were premenopausal at the time of breast cancer diagnosis.
How well are reporting guidelines and trial registration used by dermatology journals to limit bias? A meta-epidemiological study
Authors: C. Cook, J.X. Checketts, P. Atakpo, N. Nelson, M. Vassar
Journal: British Journal of Dermatology (2017)

Reporting guidelines were created to ensure research is reported in a transparent, complete manner that minimizes reporting bias. Further, these guidelines assist editors and peer reviewers when reviewing manuscripts for publication and readers when critically appraising published articles 1. Though reporting guidelines and trial registration have been associated with improved reporting quality, the full effect of these guidelines has yet to manifest because many journals do not require their use 2.

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Nivolumab for patients with metastatic uveal melanoma previously untreated with ipilimumab: A single-institutional retrospective study
Authors: K. Namikawa, A. Takahashi, A. Tsutsumida, T. Mori, N. Motoi, S. Jinnai, Y. Kage, Y. Muto, E. Nakano, N. Yamazaki
Journal: Annals of Oncology (2017)
Editorial: Tumor Necrosis Factor Antagonists: Killing Two Birds With One Biologic Stone
Authors: Joan M. Bathon, Jon T. Giles, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2017)

Forty years have passed since it was first recognized that patients with autoimmune rheumatic disease have an increased risk of fatal and non-fatal cardiovascular (CV) events (1) Although initial reports focused on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), similar findings were verified subsequently in patients with psoriasis (Ps) and/or psoriatic arthritis (PsA) and spondyloarthritis. An early feature of the atherosclerotic lesion is infiltration with inflammatory cells, particularly monocytes/macrophages, and the presence of these cells in mature plaque elevates the risk of plaque rupture and thrombosis (2). In the general population, modest elevations of circulating inflammatory proteins, including C-reactive protein (CRP), interleukin-6 (IL-6) and soluble endothelial adhesion proteins, are associated with an increased risk of acute CV events (3).

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Development of a Prompt Radiation Oncology Mediated Palliative Treatment (PROMPT) program for handling urgent cases at an academic hospital.
Authors: Jared R. Robbins, Monica Shukla, Manpreet Bedi, Candice Aitken Johnstone
Journal: Journal of Clinical Oncology (2017)

173 Background: Oncology inpatients frequently need urgent palliative radiation therapy (RT). Evaluating and treating these unscheduled patients adds challenge and stress to all members of the radiation oncology team. To efficiently and compassionately address these situations, and ensure prompt, evidence-based, quality treatment, we developed the PROMPT program. This included scheduling designated consult slots for emergencies, adding flexible CT simulation times, assigning palliative-specific dosimetrists, and engaging support staff to improve workflow. The purpose of this project was to evaluate the PROMPT program with various quality metrics and identify areas for further improvement. Methods: Patient data from inpatient encounters for academic year 2016-2017 (July 1, 2016 to June 30, 2017) were reviewed. The day of the consultation, reason for consult, date of simulations, and dose fractionation were recorded. Time from consult to simulation, and treatment initiation were calculated. Results: A total of 270 inpatient consults (199 new and 71 established) were evaluated. During the inpatient stay, 141 CT simulations and 121 verification simulations were performed. For those treated with palliative intent, 87% were simulated within one day of consult (72% same day, 15% next day). The median time from consult to the start of treatment was 1 day with 56% starting treatment within 1 day and 75% within 3 days. The most common reasons for RT were bone metastases (30%), brain metastases (19%), airway obstruction (15%), soft tissue masses (11%), and spinal cord compression (7%). For bone metastases, the median time from consult to end of treatment was 6 days with hypofractionated regimens being commonly employed in 86% (55% received 20 Gy in 5 fractions, and 31% received single fraction). Of those that started RT as inpatients, 13% stopped prior to completion, usually to enter hospice. Conclusions: The PROMPT program provided rapid identification of patients requiring palliative RT and an effective and efficient path from consultation to treatment. Implementing similar programs at other centers could facilitate improved care of palliative patients.
Pharmacist who helped his father die walks free after being acquitted of murder
Authors: Clare Dyer
Journal: BMJ (2017)

A pharmacist charged with murdering his elderly father in the family home with a lethal dose of stolen morphine has walked free with a suspended sentence, after pleading guilty to assisting a suicide.

Bipin Desai, 59, was acquitted of murder after the judge directed the jury to find him not guilty.

Mr Justice Green said that Desai had been “wrongly accused” of murdering his father, Dhirajlal Desai, 85, who had “repeatedly and insistently beseeched” his son to help him die. He described the son’s action as a “final act of assistance, kindness, and compassion” as his father’s carer.

Desai told police that he had given his father …
223Ra Therapy in Patients With Advanced Castration-Resistant Prostate Cancer With Bone Metastases
Authors: Maarten J. van der Doelen, Malou C.P. Kuppen, Marianne A. Jonker, Niven Mehra, Marcel J.R. Janssen, Inge M. van Oort, Winald R. Gerritsen
Journal: Clinical Nuclear Medicine (2017)

To identify pre-therapeutic variables associated with overall survival (OS) in patients treated with Ra.Data from 45 CRPC patients treated with Ra were retrospectively analyzed. All patients who received at least one Ra injection were included in the study. Cox proportional hazard regression models were used to estimate hazard ratio's (HR) and to test for association.Twenty-one patients (47%) received six Ra injections and 24 patients (53%) received one to five Ra injections. Median OS since start of Ra was 13.0 months (95% confidence interval (CI) 8.2-17.8). Patients who completed Ra therapy had a median OS of 19.7 months (95% CI 14.9-24.6), while patients who received one to five Ra injections had a median OS of 5.9 months (95% CI 3.8-8.1; P < 0.001).Univariable analysis showed poor baseline ECOG performance status (PS), baseline opioid use, lowered baseline hemoglobin, and elevated prostate-specific antigen, alkaline phosphatase and lactate dehydrogenase (LD) levels were significantly associated with OS. Multivariable Cox regression analysis demonstrated that poor baseline ECOG PS (HR 10.6) and high LD levels (HR 7.7) were pre-therapeutic variables that predicted poor OS.In a multivariable Cox regression model, good baseline ECOG PS and low LD levels were significantly associated with longer OS in patients treated with Ra. These variables may be used for stratification of CRPC patients for Ra therapy. Prospective studies to evaluate these variables are warranted, to develop a nomogram to select patients properly. In this retrospective study, predictors of overall survival in 45 metastatic castration-resistant prostate cancer patients treated with Ra therapy were evaluated. Baseline ECOG performance status and lactate dehydrogenase levels turned out to be significant in a multivariable prediction model for overall survival.
Underuse of the Sentinel Lymph Node Biopsy for High-Risk Squamous Cell Carcinoma of the Skin
Authors: Omeed Ahadiat, Shauna Higgins, Steve Kwon, Ashley Wysong
Journal: JAMA Dermatology (2017)

This study examines the underuse of the sentinel lymph node biopsy in the management of high-risk squamous cell carcinoma.
Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates
Authors: Hadeer M. Abdelaziz, Mohamed Gaber, Mahmoud M. Abd-Elwakil, Moustafa T. Mabrouk, Mayada M. Elgohary, Nayra M. Kamel, Dalia M. Kabary, May S. Freag, Magda W. Samaha, Sana M. Mortada, Kadria A. Elkhodairy, Jia-You Fang, Ahmed O. Elzoghby
Journal: Journal of Controlled Release (2017)