tbuckley/cabot-search huggingface dataset:
Abstract 16154: Head and Shoulder Elevation Improves Cerebral Perfusion Pressure During Active Compression-decompression CPR and Conventional CPR in a Porcine Cardiac Arrest Model
Authors: Johanna C Moore, Ryu Hyun Ho, Michael Lick, Adamantios Tsangaris, Scott McKnite, Anja Metzger, Jennifer Rees, Demetris Yannopoulos, Guillaume Debaty, Sang Do Shin, Taeyun Kim, Keith Lurie
Journal: Circulation (2015)

Background: Chest compressions during conventional cardiopulmonary resuscitation (C-CPR) increase arterial and venous pressures simultaneously, delivering bidirectional high pressure compression waves to the brain. It is possible that this may be detrimental neurologically and could be partially overcome by elevating the head during CPR. Previous animal study work using a tilt table has shown that a 30° head up position for the entire body during CPR significantly increases cerebral blood flow and cerebral perfusion pressure (CerPP) over a period of 5 minutes. We hypothesize that elevating the head and shoulders only will increase CerPP over a prolonged period of time with two different CPR techniques. Methods: Female farm pigs were sedated, intubated, anesthetized, and placed on a table designed to elevate the head and shoulders to 30°. After 8 min of untreated ventricular fibrillation and 2 min of automated C-CPR in the supine position, pigs were randomized to head up (HUP) or supine (SUP) CPR for 20 more min. In Group A, pigs were treated after 2 min of C-CPR with automated active compression decompression (ACD) CPR at 100 cycles/min plus an impedance threshold device (ITD), randomized to HUP (n=8) or SUP (n=8). In Group B, pigs were randomized after 2 min of C-CPR to treatment with HUP (n=7) or SUP (n=7) automated C-CPR. After 22 total min of CPR, defibrillation was performed. The primary outcome of the study was the comparison of CerPP at 22 min between HUP and SUP positions within each group. Results: After 22 min of CPR, CerPP (mmHg) was 39±7 with HUP versus 14±4 with SUP CPR (p=0.013) in Group A and 3.4±2.2 with HUP versus -6.3±2.6 with SUP CPR (p = 0.014) in Group B. There was no significant difference within groups for coronary perfusion pressure (CPP) after 22 min, but CPP trended higher with HUP in Group A (32.0 ± 4.9) versus SUP (18.8 ± 4.7)(p=0.072). The CPPs in Group B were 5.8 ± 1.1 with HUP versus 3.3±1.8 with SUP CPR, p=0.26). In Group A, 6/8 pigs were resuscitated in both positions where no pigs could be resuscitated in Group B. Conclusions: The HUP position using two different CPR techniques significantly improved CerPP over a prolonged period of time. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.
Identification of Novel Pathways of Osimertinib Disposition and Potential Implications for the Outcome of Lung Cancer Therapy
Authors: A. Kenneth MacLeod, De Lin, Jeffrey T.–J. Huang, Lesley A. McLaughlin, Colin J. Henderson, C. Roland Wolf
Journal: Clinical Cancer Research (2018)

Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor used in treatment of non-small cell lung cancer. A full understanding of its disposition and capacity for interaction with other medications will facilitate its effective use as a single agent and in combination therapy.
Validation of nuclear-localized AR-V7 on circulating tumor cells (CTC) as a treatment-selection biomarker for managing metastatic castration-resistant prostate cancer (mCRPC).
Authors: Howard I. Scher, Ryon P Graf, Nicole A. Schreiber, Eric Winquist, Brigit McLaughlin, David Lu, Sarah Orr, Martin Fleisher, Lori Lowes, Amanda K. L. Anderson, Yipeng Wang, Ryan Vance Dittamore, Alison L Allan, Gerhardt Attard, Glenn Heller
Journal: Journal of Clinical Oncology (2018)

273 Background: A previous analysis of 161 patients (pts) tested for nuclear-localized AR-V7(+) CTCs showed a therapy interaction between AR-V7 positivity and improved overall survival (OS) on taxane chemotherapy vs. androgen receptor signaling inhibitors (ARSI). To validate the use of the biomarker result for physician decision making, we prospectively analyzed an independent, multicenter, blinded, cross-sectional cohort (n = 225) to confirm a therapy interaction with AR-V7. We corrected for possible pt selection bias by the treating physician by analyzing the association of therapy to OS in low and high risk groups defined by the test cohort. Methods: Two analyses were performed: (1) the validation of a therapy interaction between AR-V7 positivity and superior OS benefit for pts treated with taxanes in the context of use for 2 nd + line pts; and (2) as the choice between ARSI or taxanes was at the discretion of the attending physician, pt risk was incorporated into the predictive biomarker assessment. A pt-specific risk score was developed from line of therapy and other covariates to stratify pts as low and high risk, and the association of AR-V7 status and OS was performed within each risk group to correct for physician decision making and address possible confounding with treatment assignment. Results: (1) A therapy interaction between AR-V7(+) pts and lower risk of death on taxanes vs. ARSI (HR: 0.23, p = 0.003, 95% CI: 0.09 – 0.61) was validated. (2) In the validation cohort, high risk AR-V7(+) pts had an OS benefit when treated with taxanes (p = 0.02) and the AR-V7(-) pts had an improved OS with ARSI therapy (p = 0.02). AR-V7 incidence was low in the low risk pts, precluding the analysis for this sub-cohort. Conclusions: The results validate that the nuclear-localized AR-V7(+) biomarker has an interaction with therapy and improved survival on taxanes. Further, when adjusting for pt risk, the biomarker is predictive of OS in the high risk group. Nuclear-localized AR-V7 protein in CTCs can aid in the decision between ARSI and taxane chemotherapy in the 2 nd or greater line of therapy for mCRPC.
WHO grade III gliomas: a 3-year institutional retrospective case series analysis of the correlation between IDH-1 mutation, Ki67 and progression free survival (2012-1015)
Authors: Aditaya Kumar, Athanasios Grivas
Journal: Neuro-Oncology (2018)

To assess the correlation between Ki67 proliferation index, IDH-1 mutation status and perform a subset analysis of progression free survival in World Health Organisation (WHO) Grade III gliomas A 3 year retrospective case series analysis. Patients newly diagnosed with pathological WHO grade III glioma 2012–2015. Electronic interrogation of case notes in NHS Greater Glasgow &amp; Clyde and Scottish National PACS. 44 patients (male:female ratio 1.2:1). Mean age was 52yrs (range: 20-74yrs). 63.6% were anaplastic astrocytomas, 18.2% anaplastoc oligodendrogliomas, 6.8% oligodendrogliomas, 9.1% were oligoastrocytoma and 2.3% were anaplastic pleomorphic xanthoastrocytoma. IDH-1 mutation occurred in 65.9% of patients. Ki67 ranged from 4–40 (IDH-1 wild type range: 4–40; IDH-1 mutated range: 6–40). Student’s t-test showed no statistical significance between IDH-1 mutation status and Ki67 index (p=0.51). Progression free survival was assessed using the Kaplan-Meier method and log-rank test was used for comparison between groups defined by IDH-1 mutation status and high versus low Ki67 proliferation index (high Ki67 ≥ 20). Ki67 status was not significantly linked to progression free survival in patients with IDH-1 mutated disease (z=1.24, p=0.22); however patients with wild type IDH-1and high Ki67 had significantly shorter progression free survival than those with low Ki67 (z=2.15, p<0.05). Contrary to the published literature we find no correlation between IDH-1 mutation status and Ki67 in grade III glioma. Progression free survival is not significantly correlated with Ki67 status in IDH-1 mutated disease. Patients with wild type IDH-1 and high Ki67 have significantly shorter progression free survival than those with low Ki67.
Anti-bullying programme is launched by orthopaedic trainees
Authors: Abi Rimmer
Journal: BMJ (2017)

A programme to tackle a culture of bullying, undermining, and harassment in trauma and orthopaedic surgery has been launched by the British Orthopaedic Trainees Association and the British Orthopaedic Association.

The #HammeritOut initiative, launched earlier this month www.bota.org.uk/hammer-it-out, is supported by several organisations, including the Academy of Medical Royal Colleges and the Royal College of Surgeons.

The initiative aims to create a “positive workplace culture” in trauma and orthopaedics.

Simon Fleming, president of the British Orthopaedic Trainees Association, said that the initiative …
PBX3 Is Part of an EMT Regulatory Network and Indicates Poor Outcome in Colorectal Cancer
Authors: Sebastian Lamprecht, Markus Kaller, Eva Marina Schmidt, Cristina Blaj, Tobias S. Schiergens, Jutta Engel, Andreas Jung, Heiko Hermeking, Thomas G.P. Grünewald, Thomas Kirchner, David Horst
Journal: Clinical Cancer Research (2018)

Purpose: Colorectal cancers are composed of phenotypically different tumor cell subpopulations within the same core genetic background. Here, we identify high expression of the TALE transcription factor PBX3 in tumor cells undergoing epithelial-mesenchymal transition (EMT), analyze PBX3 regulation, and determine clinical associations in colorectal cancer.Experimental design: We used transcriptomic and in situ analyses to identify PBX3 expression in colorectal cancer and cell biology approaches to determine its regulation and function. Clinical associations were analyzed in independent tissue collections and gene expression datasets of colorectal cancers with recorded follow-up data.Results: PBX3 was expressed in tumor cells with high WNT activity undergoing EMT at the leading tumor edge of colorectal cancers, whereas stromal cells were PBX3 negative. PBX3 expression was induced by WNT activation and by the EMT transcription factors SNAIL and ZEB1, whereas these effects were mediated indirectly through microRNA miR-200. PBX3 was required for a full EMT phenotype in colon cancer cells. On the protein level, PBX3 expression indicated poor cancer-specific and disease-free survival in a cohort of 244 UICC stage II colorectal cancers, and was associated with metastasis in a case-control collection consisting of 90 cases with or without distant metastasis. On the mRNA level, high PBX3 expression was strongly linked to poor disease-free survival.Conclusions: PBX3 is a novel indicator of EMT in colorectal cancer, part of an EMT regulatory network, and a promising prognostic predictor that may aid in therapeutic decision making for patients with colorectal cancer. Clin Cancer Res; 24(8); 1974-86. ©2018 AACR.
Less than full time trainees experience “undermining behaviour” in workplace, study finds
Authors: Matthew Limb
Journal: BMJ (2016)

More than half of surgical trainees who have taken up flexible training have experienced “undermining behaviour” in the workplace as a result, a study has found.

The reported problems included bullying and harassment by consultants and colleagues and discrimination in allocating jobs. Researchers are calling for “cultural change” to counter “unacceptable” behaviours and damaging perceptions and for flexible training to be made easier to access.

Rhiannon Harries, study leader, said that the findings were a cause for alarm. She told BMJ Careers, “The attitude to people undertaking flexible training within surgery is still very negative. We need to address the mindset of trainers, managers within the hospital setting, trainees, and medical students themselves so that it’s seen as possible to do flexible training, and it should be recognised as a growing …
RNA Biomarkers: Glycan Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection (Adv. Healthcare Mater. 3/2018)
Authors: Mo‐Yuan Shen, Jie‐Fu Chen, Chun‐Hao Luo, Sangjun Lee, Cheng‐Hsuan Li, Yung‐Ling Yang, Yu‐Han Tsai, Bo‐Cheng Ho, Li‐Rong Bao, Tien‐Jung Lee, Yu Jen Jan, Ya‐Zhen Zhu, Shirley Cheng, Felix Y. Feng, Peilin Chen, Shuang Hou, Vatche Agopian, Yu‐Sheng Hsiao, Hsian‐Rong Tseng, Edwin M. Posadas, Hsiao‐hua Yu
Journal: Advanced Healthcare Materials (2018)

In article number 1700701, Hsiao-hua Yu and co-workers purified circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This platform not only captures CTCs with high efficiency and specificity, but also, released these cells gently by a competitive-binding mechanism. The purified CTCs provide well-preserved RNA transcripts for the analysis of the expression level of several PCa-specific RNA biomarkers, which could provide clinical insights into the disease and valuable information for cancer diagnosis and therapeutics.
Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8+ T Cells
Authors: Glenn R. Bantug, Marco Fischer, Jasmin Grählert, Maria L. Balmer, Gunhild Unterstab, Leyla Develioglu, Rebekah Steiner, Lianjun Zhang, Ana S.H. Costa, Patrick M. Gubser, Anne-Valérie Burgener, Ursula Sauder, Jordan Löliger, Réka Belle, Sarah Dimeloe, Jonas Lötscher, Annaïse Jauch, Mike Recher, Gideon Hönger, Michael N. Hall, Pedro Romero, Christian Frezza, Christoph Hess
Journal: Immunity (2018)
Survival of second-line irinotecan-based chemotherapy in early relapse patients with gastric cancer after adjuvant chemotherapy: Exploratory subgroup analysis of TRICS trial.
Authors: Kazuhiro Nishikawa, Kenta Murotani, Kazumasa Fujitani, Hiroshi Inagaki, Yuske Akamaru, Shinya Tokunaga, Masakazu Takagi, Shigeyuki Tamura, Naotoshi Sugimoto, Tadashi Shigematsu, Takaki Yoshikawa, Tohru Ishiguro, Masato Nakamura, Yumi Miyashita, Satoshi Morita, Akira Tsuburaya, Junichi Sakamoto, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2018)

99 Background: Second-line chemotherapy (SLC) was reported to improve the survival of advanced gastric cancer (AGC). The TRICS trial which a randomized phase III study of second-line irinotecan plus cisplatin versus irinotecan alone in patients with AGC refractory to S-1 monotherapy, revealed that both irinotecan based chemotherapies were effective with favorable long-term survivals and generally well tolerated. Eligible patients included patients with recurrence within 6 months after the completion of adjuvant therapy with S-1 (early relapse cases), or patients with tumor progression after first-line S-1 for an advanced cancer (progressive cases), in this trial. However, it is unclear whether survivals in early relapse cases were different from these in progressive cases or not. Methods: A total of 168 patients registered to the TRICS trial were classified as early relapse group (n = 111) or progressive group (n = 57), and 168 (irinotecan plus cisplatin, early relapse 56/83, 67%; irinotecan alone, 55/85, 65%) and 163 (55/81, 68%; 53/82, 65%) patients were analyzed for survival. Adjusted OS and adjusted PFS were constructed adjusted Kaplan-Meier curve with inverse probability weight, and were estimated by inverse probability of treatment weighting method (IPTW). Results: In baseline characteristics, PS 0 were more frequently seen in early relapse group than in progressive group (86% vs 72%, p = 0.0328), and median age of early relapse group was younger than progressive group (66 vs 72, p = 0.0162). The median OS was 13.9 months in early relapse group and 10.0 months in progressive group (HR:0.746, p = 0.1019). The adjusted median OS was 14.0 months in early relapse group and 10.6 months in progressive group (IPTW HR:0.864, p = 0.1019). Early relapse group showed better trends in PFS compared to the progressive group (4.7M vs 3.6M, HR: 0.650, p = 0.0149). The adjusted median PFS was 4.8 months in early relapse group and 3.7 months in progressive group (IPTW HR:0.673, p = 0.0008). Conclusions: Irinotecan based chemotherapies were effective especially in early relapse cases after adjuvant therapy with S-1, in second-line setting of AGC.
Addressing sexual health among women who use substances in the marginal urban communities of Latin America: an ethnographic analysis and pilot survey
Authors: Laura R Glasman, Julia Dickson Gomez, Gloria Bodnar, Wendy Cuellar
Journal: The Lancet Global Health (2018)

BackgroundIn marginal urban communities in Latin America, female substance users are at high risk of HIV, sexually transmitted infections (STIs), and unintended pregnancies, which result, in part, from community violence and cultural sanctions against women who use substances. We did formative research and pilot work to develop what may be the first integrated sexual health intervention for Latin American female substance users. We specifically aimed to adapt a multilevel HIV prevention programme for crack users to the circumstances of female substance users in marginal urban communities of San Salvador, El Salvador. We hypothesised that contexts that stigmatise female sex and substance use and condone violence hinder female substance users' service use and make them more dependent on men and vulnerable to sexual coercion.MethodsFrom Nov 1, 2015, to Dec 31, 2016, we conducted ethnographic observations and mapped organisations that served women in a large marginal community. We also undertook focus groups and a pilot survey to identify female substance users' perceptions of services and experiences of stigma. Finally, we implemented "plan, study, and act" circles to adapt and pilot test peer-counselling sessions with networks of female substance users, which addressed the interpersonal context of female substance users' sexual health with partners and providers.FindingsWe did not find any services directed to female substance users, and organisations targeting women were unaware of the problem. In focus groups (n=18), women reported fear of being judged for using drugs, especially when pregnant or caring for children. Women reported avoiding services or hiding their substance use from providers and receiving verbal aggression from health-care staff. In surveys (n=38), 24 (64%) female substance users who would not request HIV testing would accept it from a friend and nearly all felt more comfortable with integrated HIV/STI and pregnancy prevention than with standalone services. Women in the counselling sessions (n=16) reported more equitable gender norms and safer sex motivations, and greater self-efficacy to prevent sexual coercion than women in a control group (n=18).InterpretationInterventions to address female substance users' sexual health in these communities should (a) raise awareness of gender norms and associated stigmas; (b) train health-care staff to identify female substance use and address female substance users' sexual health; (c) provide peer-referrals of female substance users to integrated services; and (d) empower female substance users' networks to decrease their vulnerability to coercion and to develop skills to communicate with providers.FundingUS National Institute of Mental Health 5P30MH052776-22 and P30MH052776-23.
AUTOMATED DATA EXTRACTION FROM ELECTRONIC HEALTH RECORDS TO CREATE NOVEL PROGNOSTIC MODELS FOR PERIPHERAL ARTERY DISEASE
Authors: Adelaide Maria Arruda-Olson, Naveed Afzal, Vishnu Priya Mallipeddi, Ahmad Said, Homam Moussa Pacha, Alisha Chaudhry, Christopher Scott, Kent Bailey, Thom Rooke, Paul Wennberg, Vinod Kaggal, Iftikhar Kullo, Rajeev Chaudhry, Hongfang Liu
Journal: Journal of the American College of Cardiology (2018)
Department of Health invests £650 000 in support groups for healthcare staff
Authors: Helen Jaques
Journal: BMJ (2013)

The Department of Health is investing £650 000 to expand a scheme that supports NHS staff in discussing difficult emotional and social issues that arise from patient care.

Schwartz Center Rounds, developed by the Schwartz Center for Compassionate Healthcare in Boston, bring multidisciplinary staff together for an hour’s meeting each month to discuss a particular patient’s case and how the staff feel about the …
Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer
Authors: S.M. de Boer, B.G. Wortman, T. Bosse, M.E. Powell, N. Singh, H. Hollema, G. Wilson, M.N. Chowdhury, L. Mileshkin, J. Pyman, D. Katsaros, S. Carinelli, A. Fyles, C.M. McLachlin, C. Haie-Meder, P. Duvillard, R.A. Nout, K.W. Verhoeven-Adema, H. Putter, C.L. Creutzberg, V.T.H.B.M. Smit
Journal: Annals of Oncology (2017)

BackgroundIn the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methodsA total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).ResultsIn the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).ConclusionCentral pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved.This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).
RECOMBINANT HUMAN NEUREGULIN-1 REDUCES THE EXPRESSION OF NOX4 BY ACTIVATING ERK1/2 TO ALLEVIATE MYOCARDIAL ISCHEMIA REPERFUSION INJURY
Authors: Fuhua Wang, Xuejing Liu, Haiyi Yu, Xiaomin Huang, Wei Huang, Guisong Wang
Journal: Journal of the American College of Cardiology (2018)
TEMPORAL CHANGES IN STATIN PRESCRIPTION AND INTENSITY AT DISCHARGE AFTER AN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) EVENT: REAL-WORLD EXPERIENCE IN A LARGE INTEGRATED HEALTHCARE SYSTEM - THE IMPRES STUDY
Authors: Jeffrey L. Anderson, Kirk U. Knowlton, Heidi May, Tami Bair, Donald Lappe, J. Muhlestein
Journal: Journal of the American College of Cardiology (2018)
ACUTE AND SHORT TERM PERFORMANCE OF MAGMARIS BIORESORBABLE SCAFFOLD IMPLANTATION IN COMPLEX LESIONS: A MULTICENTER EXPERIENCE
Authors: Francesco Tomassini, Enrico Cerrato, Giorgio Quadri, Alfonso Ielasi, Cristina Rolfo, Dario Buccheri, Caramanno Giuseppe, Massimo Leoncini, Fabio Ferrari, Francesco Granata, Gianluca Campo, Paolo Sganzerla, Claudio Rapetto, Biscaglia Simone, Nadia Garro, Giorgio Sacchetta, Chiara Bernelli, Enrico Geraci, Ferdinando Varbella
Journal: Journal of the American College of Cardiology (2018)