tbuckley/cabot-search huggingface dataset:
In vitro and in vivo efficacy of the combined treatment of 150 khz tumor treating fields (TTFields) and sorafenib in hepatocellular carcinoma.
Authors: Uri Weinberg, Shiri Davidi, Karnit Gotlib, Einav Zeevi, Catherine Tempel- Brami, Rosa S. Schneiderman, Tali Voloshin, Moshe Giladi, Adrian Kinzel, Eilon David Kirson, Yoram Palti
Journal: Journal of Clinical Oncology (2019)

333 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. The aim of this work is to explore the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. N1S1 HCC cells were injected to the left lobe of the liver of SD rats. After 1 week, TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days and tumor growth was followed using MRI. Healthy rats were used to study safety of the use of TTFields (150 kHz) applied to the abdomen. Results: The optimal TTFields frequency was found to be 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 53-64% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number cells (2-way ANOVA, p &lt; 0.001) as compared to each treatment alone. Tumor growth was significantly reduced by the combined group compared to the control group (student t test, p &lt; 0.01). Safety studies did not reveal any adverse event associated with TTFields application to the rat abdomen. Conclusions: The results presented in this work demonstrate that TTFields can be a safe and effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.
Risk Factors for the Development of Cutaneous Melanoma after Allogeneic Hematopoietic Cell Transplantation
Authors: Megan Herr, Rochelle E. Curtis, Margaret A. Tucker, Heather R. Tecca, Eric A. Engels, Elizabeth Cahoon, Minoo Battiwalla, David K. Buchbinder, Mary E. D. Flowers, Ruta Brazauskas, Bronwen E. Shaw, Lindsay M. Morton
Journal: Blood (2018)
Incidence of pulmonary metastasis among patients with colorectal adenocarcinoma: Correlation between sidedness and RAS mutations.
Authors: Lara Azevedo Diniz, Diogo De Brito Sales, Larissa Machado, Amanda Karani, Milton Jose Barros, Rodrigo Gomes Taboada, Natasha Carvalho Pandolfi, Poliana de Andrade, Helano C. Freitas
Journal: Journal of Clinical Oncology (2019)

527 Background: Sidedness alongside with RAS status in colorectal adenocarcinoma has been proved to correlate with survival and response to systemic therapy. There are few data reporting how these clinical characteristics can predict the dissemination of metastasis. We hypothesize that lung metastasis were more common among those with RAS mutations and left colon primary cancers. Methods: In this study, 609 patients with stage I to IV colorectal adenocarcinoma were enrolled retrospectively. Patients were divided by sidedness, right and left and were also classified according to KRAS and NRAS status. The frequencies of lung metastasis were analyzed among the different groups. Results: Of the 609 patients analyzed, 129 (21.1%) had recurrent disease and 206 (33.8%) had synchronous metastasis. RAS status was available in 311 (92.8%) of the metastatic patients and 138(44.4%) were wild type. We found that 60 (34.7%) of the patients with RAS mutated tumors presented with metachronic or synchronous lung metastasis compared with 31 (22.5%) of the wild-type population (p = 0.019). Focusing only on sidedness, excluding rectal cancer since its already described increased incidence of lung metastasis, 47 (29.7%) of the patients with left sided colon cancer had lung metastasis compared with 8 (11.1%) of the right sided primary population (p = 0,002). It was observed similar frequencies of RAS mutations among patients with left (54.1%) and right (57.6%) sided tumor. Conclusions: RAS mutated colorectal adenocarcinoma is associated with an increased incidence of lung metastasis as well as left sided tumors where this finding seems to be independent of RAS status.
Tumor Microenvironment Regulation by the Endoplasmic Reticulum Stress Transmission Mediator Golgi Protein 73 in Mice
Authors: Congwen Wei, Xiaoli Yang, Ning Liu, Jin Geng, Yanhong Tai, Zhenyu Sun, Gangwu Mei, Pengyu Zhou, Yumeng Peng, Chenbin Wang, Xiaoli Zhang, Pingping Zhang, Yunqi Geng, Yujie Wang, Xiaotong Zhang, Xin Liu, Yanhong Zhang, Feixiang Wu, Xiang He, Hui Zhong
Journal: Hepatology (2019)

The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor‐promoting inflammation by up‐regulating UPR target genes and proinflammatory cytokines. However, the molecular basis of this endoplasmic reticulum (ER) stress transmission remains largely unclear. Here, we identified the secreted form of Golgi protein 73 (GP73), a Golgi‐associated protein functional critical for hepatocellular carcinoma (HCC) growth and metastasis, is indispensable for ER stress transmission. Notably, ER stressors increased the cellular secretion of GP73. Through GRP78, the secreted GP73 stimulated ER stress activation in neighboring macrophages, which then released cytokines and chemokines involved in the tumor‐associated macrophage (TAM) phenotype. Analysis of HCC patients revealed a positive correlation of GP73 with glucose‐regulated protein 78 (GRP78) expression and TAM density. High GP73 and CD206 expression was associated with poor prognosis. Blockade of GP73 decreased the density of TAMs, inhibited tumor growth, and prolonged survival in two mouse HCC models. Conclusion : Our findings provide insight into the molecular mechanisms of extracellular GP73 in the amplification and transmission of ER stress signals.
NIHR’s research signals in <i>The BMJ</i>
Authors: Sophie Cook, Tara Lamont, Rob Cook, Tansy Evans, Peter Davidson
Journal: BMJ (2019)

Decisions in healthcare are complex and different for every person.Keeping up to date with new research and guidance is key to dealing with uncertainty and delivering high quality personalised care.Both clinicians and patients need robust summaries and shortcuts to help put the findings of new studies into the context of wider evidence and clinical guidelines.With at least 75 trials and 11 systematic reviews published every day (numbers are likely to have risen since this 2010 estimate), 1 filters and selection processes are needed.
Atopic Asthma as an Unrecognized Risk Factor for Kawasaki Disease: A Population-Based Case-Control Study
Authors: Bong Seok Choi, Editt Nikoyan, Chung-Il Wi, Katherine S. King, Euijung Ryu, Youn Ho Sheen, Hee Yun Seol, Thomas G. Boyce, Jonathan N. Johnson, Young J. Juhn
Journal: Journal of Allergy and Clinical Immunology (2019)
Consolidative High Dose Chemotherapy and Autologous Stem Cell Transplant for Patients with Primary Central Nervous System (CNS) Lymphoma or Non-Hodgkin Lymphoma with CNS Involvement Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen
Authors: Patricia A. Young, Daria Gaut, Davis A. Kimaiyo, Jonathan A. Grotts, John P Chute, Gary J. Schiller, John M. Timmerman, Sven de Vos, Herbert A. Eradat
Journal: Blood (2018)
A phase Ib study of pembrolizumab (Pem) in combination with stereotactic body radiotherapy (SBRT) for resectable liver metastatic colorectal cancer (CRC).
Authors: Anita Ahmed Turk, Sam Joseph Lubner, Nataliya Volodymyrivna Uboha, Noelle K. LoConte, Daniel Mulkerin, David H. Kim, Kristina Matkowskyj, Sharon M. Weber, Daniel Abbott, Jens C. Eickhoff, Michael F. Bassetti, Dustin A. Deming
Journal: Journal of Clinical Oncology (2019)

680 Background: Adjunctive therapies are essential to enhance the effect of anti-PD1 therapies for the treatment of microsatellite stable (MSS) colorectal cancer. SBRT is utilized to treat liver metastatic CRC, causing an increase in immunogenic intratumoral and a rapid influx of responding immune cells. We hypothesize that radiation enhances immunogenicity of MSS CRC and potentiates effectiveness of PD-1 blockade. This phase Ib study examines the safety and efficacy of the sequential combination of SBRT and Pem in patients for whom the goal is to resect all sites of known disease. Methods: Key eligibility criteria include MSS CRC with liver-confined metastatic disease with the therapeutic goal of resection of all radiographic disease with one operation. Subjects must be a candidate for SBRT to 1-3 liver metastases. Prior surgery and systemic chemotherapy are allowed. Subjects receive sequential SBRT and cycle 1 of Pem prior to operative management. Postoperatively, patients complete cycles 2-9 of Pem followed by scheduled surveillance with imaging every 12 weeks. The primary objectives are to determine the safety of this regimen and the recurrence rate at one year following clearance of metastatic disease. Secondary objectives include time to recurrence, DFS, and OS. Results: Nine patients (median age 61.5 [range 39-69]) have completed the intended neoadjuvant therapy, operative management and at least one adjuvant cycle of Pem. All patients received prior FOLFOX. Any-grade AEs (&gt; 20%) through cycle 2 of Pem attributable to SBRT include fatigue (44%) and nausea (22%). Any-grade AEs related to Pem include lymphopenia (25%). Postoperative AEs included one case of biliary tract injury and biloma, not related to immunotherapy. One patient developed a rash following SBRT and Pem which may be an immunotherapy-related toxicity. No grade 3/4 immunotherapy AEs have occurred. Conclusions: The combination of SBRT, Pem, and surgical resection is well tolerated with no signal of increased immunotherapy-related toxicity. Clinical trial information: NCT02837263.
Maternal socioeconomic position and psoriasis
Authors: J. Groot, A.M. Nybo Andersen, A. Adam, T.E. Tind Nielsen, C. Blegvad, L. Skov
Journal: British Journal of Dermatology (2019)

Psoriasis is a common skin disease that is often characterized by well‐defined red or scaly patches on the skin. The disease affects approximately 0.4 percent of children in Denmark, with similar rates in other western countries. Psoriasis occurring in childhood may be referred to as paediatric‐onset psoriasis. In this Danish study, the authors aimed to find out whether children with a lower socioeconomic position (from families with lower education, income and employment) were more likely to suffer from paediatric‐onset psoriasis compared to those with a higher socioeconomic position. The authors used data from a study in which mothers and their children participated from pregnancy and the children's birth until the children were 11 years old. At the 11‐year follow‐up of children, mothers were asked whether their child had psoriasis. Information on socioeconomic position was gathered by using data from official databases on the mothers’ income, education and work. The authors investigated whether these factors affected the chances of their child developing paediatric‐onset psoriasis and found that they were strongly related. Children whose mothers had a lower education or income were more likely to have paediatric‐onset psoriasis than children whose mothers had a higher education or income. Social and economic circumstances at birth and in childhood appear to play a role in the risk of getting paediatric‐onset psoriasis.
Rethinking medicine: patients have feelings too
Authors: Richard Fitton
Journal: BMJ (2019)

In his book, Medical Nemesis , Ivan Illich says that doctors have misappropriated patients’ health—understandably with the advent of bacteriology, pharmacology, histology, anaesthetics, surgery, imaging, laboratory testing, and scientific medicine. Today, patients have greater knowledge and access to information, so an adult to adult relationship between doctors and the public is necessary.1

In 2000, my …
Evaluation and accurate diagnoses of pediatric diseases using artificial intelligence
Authors: Huiying Liang, Brian Y. Tsui, Hao Ni, Carolina C. S. Valentim, Sally L. Baxter, Guangjian Liu, Wenjia Cai, Daniel S. Kermany, Xin Sun, Jiancong Chen, Liya He, Jie Zhu, Pin Tian, Hua Shao, Lianghong Zheng, Rui Hou, Sierra Hewett, Gen Li, Ping Liang, Xuan Zang, Zhiqi Zhang, Liyan Pan, Huimin Cai, Rujuan Ling, Shuhua Li, Yongwang Cui, Shusheng Tang, Hong Ye, Xiaoyan Huang, Waner He, Wenqing Liang, Qing Zhang, Jianmin Jiang, Wei Yu, Jianqun Gao, Wanxing Ou, Yingmin Deng, Qiaozhen Hou, Bei Wang, Cuichan Yao, Yan Liang, Shu Zhang, Yaou Duan, Runze Zhang, Sarah Gibson, Charlotte L. Zhang, Oulan Li, Edward D. Zhang, Gabriel Karin, Nathan Nguyen, Xiaokang Wu, Cindy Wen, Jie Xu, Wenqin Xu, Bochu Wang, Winston Wang, Jing Li, Bianca Pizzato, Caroline Bao, Daoman Xiang, Wanting He, Suiqin He, Yugui Zhou, Weldon Haw, Michael Goldbaum, Adriana Tremoulet, Chun-Nan Hsu, Hannah Carter, Long Zhu, Kang Zhang, Huimin Xia
Journal: Nature Medicine (2019)
Phase 2 trial of durvalumab and radiation revaccination in patients with metastatic adenocarcinoma of the pancreas who have progressed through first-line chemotherapy.
Authors: Michael David Chuong, Shahed Nicolas Badiyan, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2019)

TPS461 Background: Emerging data suggest that immunotherapy combined with radiation therapy (RT) can lead to robust anti-tumor immune responses within many tumor types. While not highly immunogenic, pancreatic cancer has been shown to respond to immunotherapy especially when combined with RT. Our research hypothesis is that the combination of RT and immunotherapy (durvalumab) is well tolerated and stimulates a clinically significant pancreas-cancer specific immune response. Methods: Metastatic pancreatic cancer patients who have progressed through first-line chemotherapy will receive durvalumab every 4 weeks and will concurrently receive 24 Gy in 3 daily fractions to one pancreatic cancer lesion during week 3 followed by 24 Gy in 3 daily fractions to a second lesion during week 5. Durvalumab will continue until disease progression or unacceptable toxicity. Two lesions (instead of only one) will receive RT sequentially because of the potential for radiation “revaccination” to generate a more robust anti-tumor immune response, as our group previously published from a pancreas cancer mouse model. The primary objective is to evaluate whether the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data. Secondary endpoints include evaluation of toxicity, overall survival, overall response rate, clinical benefit rate, and time to in-field progression. We will evaluate whether there is any correlation between durvalumab plus RT and levels of CD8 T cells, regulatory T cells, or myeloid derived suppressor cells in the peripheral blood at various intervals before, during, and after therapy. We will use a 1-sided test with a 5% significance level (a) to test the uni-directional hypothesis that the median PFS is prolonged from 3 to 4.5 months by combining RT with durvalumab. With a statistical power (1-b) of the study of 80%, we estimate an accrual time of 26 months for a total sample size of 39 patients. A positive signal from this trial that RT revaccination with concurrent checkpoint inhibitor is effective and well tolerated would provide support for a randomized trial. Clinical trial information: NCT03490760.
Abstract 18252: "Appropriate Use" of In-Hospital Telemetry Services in the Modern Era: Insights From a Review of 177 Consecutive Code Blues
Authors: Christopher A Woolley, Scot W Nolan, Jill Waalen, Bruce J Kimura
Journal: Circulation (2017)

Background: Although the 1991 ACC guidelines and 2004 AHA practice standards for telemetry(T) reflect the historical benefit of early monitoring for arrhythmias in select admissions, few data exist on contemporary inpatients referred for T who later suffer a “code blue.” Objective: We sought to review the appropriate use of T, detection of causative arrhythmias, and the timing and outcomes for code blues in a tertiary hospital. Methods: Over a 3-year period in a 300-bed teaching hospital with 48% T beds, data that had been formally recorded from all inpatient ward “code blues” were reviewed and the code etiology categorized as arrhythmogenic(ARR) or nonarrhythmogenic(nonARR). A “code blue” event was defined as the activation of the hospital’s code team and the subsequent application of ACLS. Events in the ICU, operating or emergency rooms were excluded. The presence and length of T prior to the code, appropriateness (Class I/II vs. III) by AHA guidelines, and presence of a causative arrhythmia were record...
Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy
Authors: Kinsie E Arnst, Souvik Banerjee, Hao Chen, Shanshan Deng, Dong‐Jin Hwang, Wei Li, Duane D Miller
Journal: Medicinal Research Reviews (2019)

Microtubule (MT)-targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Newer generations of developed drugs attack these problems and alternative approaches such as the development of dual tubulin and kinase inhibitors are being investigated. This approach offers the potential to show increased efficacy and lower toxicities. This review covers different categories of MT-targeting agents, recent advances in dual inhibitors, and current challenges for this drug target.
Early Cytomegalovirus Reactivation and Donor Constellation Reduce Early and Late Relapse Incidence of Acute Myeloid Leukemia in a Long-Term Study
Authors: Amin T. Turki, Nikolaos Tsachakis-Mück, Saskia Leserer, Ji-Hee Yi, Evren Bayraktar, Rashit Bogdanov, Tobias Liebregts, Nina Kristin Steckel, Melanie Fiedler, Dietrich W. Beelen
Journal: Blood (2018)
Publisher Correction: c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells
Authors: Leona Gabryšová, Marisol Alvarez-Martinez, Raphaëlle Luisier, Luke S. Cox, Jan Sodenkamp, Caroline Hosking, Damián Pérez-Mazliah, Charlotte Whicher, Yashaswini Kannan, Krzysztof Potempa, Xuemei Wu, Leena Bhaw, Hagen Wende, Michael H. Sieweke, Greg Elgar, Mark Wilson, James Briscoe, Vicki Metzis, Jean Langhorne, Nicholas M. Luscombe, Anne O’Garra
Journal: Nature Immunology (2019)
Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial
Authors: Bertrand Tombal, Fred Saad, David Penson, Maha Hussain, Cora N Sternberg, Robert Morlock, Krishnan Ramaswamy, Cristina Ivanescu, Gerhardt Attard
Journal: The Lancet Oncology (2019)
Intravenous Administration of Recombinant Factor VIII Induces Immune Tolerance to Subcutaneous Turoctocog Alfa Pegol (SC N8-GP) in Humanized Hemophilia A Mice
Authors: Stine Louise Reedtz-Runge, Karin Weldingh, Heidi Schiøler Schultz, Anders Holm Millner, Frederik Rode, Bo Wiinberg, Mads Kjelgaard-Hansen
Journal: Blood (2018)
Days’ Supply of Initial Opioid Analgesic Prescriptions and Additional Fills for Acute Pain Conditions Treated in the Primary Care Setting — United States, 2014
Authors: Mallika L. Mundkur, Jessica M. Franklin, Younathan Abdia, Krista F. Huybrechts, Elisabetta Patorno, Joshua J. Gagne, Tamra E. Meyer, Judy Staffa, Brian T. Bateman
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During 2017, opioids were associated with 47,600 deaths in the United States, approximately one third of which involved a prescription opioid (1). Amid concerns that overprescribing to patients with acute pain remains an essential factor underlying misuse, abuse, diversion, and unintentional overdose, several states have restricted opioid analgesic prescribing (2,3). To characterize patterns of opioid analgesic use for acute pain in primary care settings before the widespread implementation of limits on opioid prescribing (2,3), patients filling an opioid analgesic prescription for acute pain were identified from a 2014 database of commercial claims. Using a logistic generalized additive model, the probability of obtaining a refill was estimated as a function of the initial number of days supplied. Among 176,607 patients with a primary care visit associated with an acute pain complaint, 7.6% filled an opioid analgesic prescription. Among patients who received an initial 7-day supply, the probability of obtaining an opioid analgesic prescription refill for nine of 10 conditions was <25%. These results suggest that a ≤7-day opioid analgesic prescription might be sufficient for most, but not all, patients seen in primary care settings with acute pain who appear to need opioid analgesics. However, treatment strategies should account for patient and condition characteristics, which might alternatively reduce or extend the anticipated duration of benefit from opioid analgesic therapy.
Abstract 17399: Sex Differences in the Rate of 30-Day Readmission After Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Luke Lam, Hyeong Jun Ahn, Kazue Okajima, Katie Schoenman, Todd B Seto, Ralph V Shohet, Jill Miyamura, Tetine L Sentell, Kazuma Nakagawa
Journal: Circulation (2017)

Background: Sex differences in the 30-day readmission rate of patients treated with percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI) have been inadequately studied. ...