tbuckley/cabot-search huggingface dataset:
Trainee doctors could be taken out of London accident and emergency department
Authors: Clare Dyer
Journal: BMJ (2016)

A London hospital’s accident and emergency unit is being threatened with closure on safety grounds by the bodies responsible for approving and organising junior doctors’ training, for the first time in NHS history.

The General Medical Council is so worried about the risk to the safety of patients from the shortage of senior and middle grade emergency doctors at North Middlesex Hospital in north London that it has used its powers for the first time to issue a “pre-statutory letter,” warning that it could withdraw approval for junior doctors to be trained at the unit.

The letter was sent on 21 May to Health Education England, which arranges training posts. In the …
Targeting Cyclin D-CDK4/6 Sensitizes Immune-Refractory Cancer by Blocking the SCP3–NANOG Axis
Authors: Se Jin Oh, Hanbyoul Cho, Suhyun Kim, Kyung Hee Noh, Kwon-Ho Song, Hyo-Jung Lee, Seon Rang Woo, Suyeon Kim, Chel Hun Choi, Joon-Yong Chung, Stephen M. Hewitt, Jae-Hoon Kim, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Hae-Chul Park, Tae Woo Kim
Journal: Cancer Research (2018)

Immunoediting caused by antitumor immunity drives tumor cells to acquire refractory phenotypes. We demonstrated previously that tumor antigen-specific T cells edit these cells such that they become resistant to CTL killing and enrich NANOGhigh cancer stem cell-like cells. In this study, we show that synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, is overexpressed in immunoedited cells and upregulates NANOG by hyperactivating the cyclin D1-CDK4/6 axis. The SCP3-cyclin D1-CDK4/6 axis was preserved across various types of human cancer and correlated negatively with progression-free survival of cervical cancer patients. Targeting CDK4/6 with the inhibitor palbociclib reversed multiaggressive phenotypes of SCP3high immunoedited tumor cells and led to long-term control of the disease. Collectively, our findings establish a firm molecular link of multiaggressiveness among SCP3, NANOG, cyclin D1, and CDK4/6 and identify CDK4/6 inhibitors as actionable drugs for controlling SCP3high immune-refractory cancer.Significance: These findings reveal cyclin D1-CDK4/6 inhibition as an effective strategy for controlling SCP3high immune-refractroy cancer. Cancer Res; 78(10); 2638-53. ©2018 AACR.
Abstract 20304: Erythrocyte Aging as a Mechanism of Anemia and a Biomarker of Device Thrombosis in Continuous-Flow Left Ventricular Assist Devices
Authors: Ziad Taimeh, Ryan Koene, Julie Furne, Ashish Singal, Peter Eckman, Michael Levitt, Marc Pritzker
Journal: Circulation (2016)

Background: Blood injury caused by continuous-flow left ventricular assist devices (CF-LVAD) has been associated with device thrombosis and anemia. Accurate in-vivo quantification of erythrocyte tu...
INTRAOPERATIVE GRAFT ANGIOGRAPHY AS A METHOD OF ANASTOMOSIS QUALITY CONTROL POST CORONARY ARTERY BYPASS GRAFTING PROCEDURE
Authors: Cristina Sanina, Leo Bockeria, Olga Bockeria, Karen Petrosian, Manolis Pursanov, V. Shvartz, M. Biniashvili
Journal: Journal of the American College of Cardiology (2018)
Observational analysis of IDO-1 expression in MEL samples assessed using an RNAscope assay.
Authors: Robert Charles Newton
Journal: Journal of Clinical Oncology (2018)

53 Background: IDO-1 catalyzes the degradation of trp to kyn and can promote tumor escape from host immunosurveillance. IDO-1 expression evaluation has potential importance in identification of a population with worse prognosis and is important in the clinical evaluation of IDO-1 inhibitors. We have developed an optimized assay for IDO-1 specific message detection using RNAscope technology (RST) and applied it to an analysis of human melanoma (MEL) samples. Methods: 25 MEL samples were evaluated for IDO-1 by IHC and the samples used to optimize the RST assay. IDO-1 expression could be demonstrated in tumor cells (TC) as well as in immune cells (IC) infiltrating the tumor and in IC in the peritumoral area. A scoring method was developed to classify IDO-1 expression in all three populations. An H-score of 5 or greater was used as an arbitrary cutoff for IDO-1 positivity. An additional 27 MEL samples, collected as part of the ECHO202/KN037 study of epacadostat in combination with pembrolizumab, were evaluated. Results: IHC for IDO-1 showed 24% positive samples for tumor expression. As expected based on enhanced sensitivity, RST identified 56% as positive – 83% of the samples were positive by both assays. With IHC, 60% were positive for intratumoral IC expression of IDO-1 while RST identified 68% as positive for IC expression – 93% of the samples were positive by both methods. Analysis of the samples from the ECHO 202 study showed that 85% were positive for TC IDO-1 expression, while 59% were positive for IC IDO-1 expression with 52% positive for both. Of 22 PD-L1+ samples, 20 were positive for IDO-1 in either TC or IC. Of PD-L1- samples, 4 were positive for IDO-1 in either TC or IC. There was a trend toward higher IDO-1 expression in PD-L1+ tumors. In this data set there was no association of IDO-1 expression with BRAF mutation status, elevated LDH or prior exposure to immune therapies. Conclusions: RST detection has the potential to provide a robust and quantitative assay to evaluate IDO1 expression in TC and IC. Further refinement of this assay and determination of its utility in assessing predictors of patient response in MEL patients undergoing combination therapy with epacadostat and pembrolizumab will take place in ECHO-301/KN252 (NCT02752074).
Medical careers should be open to more young people, says HEE
Authors: Abi Rimmer
Journal: BMJ (2014)

Careers in medicine should be opened up to a wider talent pool, Health Education England has said. In a document setting out its proposed strategy for widening participation in NHS careers, HEE said that improving access to careers in medicine was a “particular priority.”1

The strategy announcement comes after a move by the Medical Schools Council to commission research into widening medical schools’ selection processes to increase participation by students from disadvantaged backgrounds.2 …
Association between survival and non-selective prehospital aspirin and heparin administration in patients with out-of-hospital cardiac arrest: a propensity score-matched analysis
Authors: Ulrich Grabmaier, Konstantinos D. Rizas, Julius Berghof, York Huflaender, Christopher Wiegers, Reza Wakili, Michael Kaspar, Matthias Angstwurm, Steffen Massberg, Ludwig T. Weckbach, Stefan Brunner
Journal: Intensive Care Medicine (2018)
Intrapartum cardiotocography and pattern recognition
Authors: Shashikant L Sholapurkar
Journal: BMJ (2018)

Mullins and Lees debate Brocklehurst about the use of continuous fetal heart rate monitoring.1 The INFANT trial did not test cardiotocography versus intermittent or no auscultation, but rather whether decision support software could aid interpretation of cardiotocographs. The counterargument offered for the major flaw of “learning in the control group” was that some people have “intrinsic pattern recognition inability” that is not improved by training.2 But this inability cannot …
On-call rooms should be available to lessen risks of driving after night shifts
Authors: Helen Jaques
Journal: BMJ (2012)

Junior doctors have demanded that hospitals reinstate free on-call rooms so that trainees can get some rest during or after night shifts, so as to reduce their risk of crashes when driving home at the end of a shift.

Tom Berry, chairman of the BMA’s Scottish junior doctors committee, told the association’s junior doctors conference that driving after a night shift, especially a long or busy shift, triples the chance of a crash. 

The risk is particularly pronounced after a doctor’s first night shift, when they may have been …
Association of the neutrophil-to-lymphocyte ratio prior to checkpoint blockade immunotherapy (CBI) or radiation plus CBI with overall survival in melanoma patients.
Authors: Terence Duane Rhodes, Gail Fulde, Robin Romero, Tyler Abraham, Bryce Moulton, Margaret Van Meter, Ramya Thota, Mark Andrew Lewis, Derrick S. Haslem, Lincoln Nadauld, Tyler Barker
Journal: Journal of Clinical Oncology (2018)

200 Background: Studies in certain cancer types have indicated that radiation therapy prior to the use of CBI provides a survival benefit. This benefit has not been clearly defined for patients with metastatic melanoma. Additionally, the neutrophil-to-lymphocyte ratio (NLR) may be a potential biomarker. Methods: This retrospective study was performed in patients diagnosed with melanoma between January 2007 and August 2016 who received CBI with or without previous radiation treatment at Intermountain Healthcare (Utah, USA). Cases were identified from electronic medical records and data was manually extracted through August of 2017. The neutrophil-to-lymphocyte ratio (NLR) was calculated from the absolute neutrophil and lymphocyte counts of a complete blood cell count with differentials performed as a routine standard of care procedure in melanoma patients prior to therapy initiation. Overall survival was defined as the length of time (d) from start of CBI to death as of August, 2017. Results: Forty-six melanoma patients were initially identified. Of these, thirteen patients were excluded due to lack of follow-up data (n = 9), radiation performed after CBI (n = 3), or concurrent radiation and CBI (n = 1). The final analysis consisted of 33 subjects separated below (NLR &lt; 3.12, n = 16) and above (NLR ≥ 3.12, n = 17) the NLR median. Age, height, body mass, and body mass index were not significantly different between groups (p-range: 0.11-0.60). Results from the Kaplan-Meier curve indicate that a NLR above the median associates with lower overall survival (Mantel, p = 0.04) in melanoma patients receiving CBI with or without previous radiation treatment. In a separate analysis of this cohort, overall survival was not significantly influenced by radiation therapy prior to CBI. Conclusions: Although prior radiation therapy offered no survival advantage for patients receiving CBI, NLR less than 3.12 was associated with an increase in overall survival. Further studies are need to explore NLR as a biomarker.
Impact of the T and N stage in the American Joint Committee on Cancer (AJCC) 8<sup>th</sup> edition staging system for pancreatic cancer with curative resection.
Authors: Akiko Todaka, Akira Fukutomi, Mitsuhiro Furuta, Hiromichi Shirasu, Masahiro Kawahira, Takeshi Kawakami, Yukio Yoshida, Sadayuki Kawai, Satoshi Hamauchi, Takahiro Tsushima, Tomoya Yokota, Nozomu Machida, Kentaro Yamazaki, Yusuke Onozawa, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2018)

261 Background: The 8 th edition of the AJCC staging system for pancreatic cancer contains several changes. T and N classification incorporate tumor size and number of positive lymph node (LN). The aim of this study was to evaluate the impact on the outcomes of the new classification for the patients who underwent curative resection and received adjuvant treatment with S-1. Methods: We retrospectively reviewed 96 patients who underwent curative resection for pancreatic ductal adenocarcinoma and received adjuvant treatment with S-1 (40, 50, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14-day rest, every 6 weeks [one cycle], for up to four cycles) at our institution between January 2007 and December 2015. Inclusion criteria were as follows: PS0/1, adequate-organ functions, no critical complication, start of adjuvant therapy within 10 weeks after resection, and no active concomitant malignancy. Results: 66 patients were satisfied with these criteria. Patients characteristics were as follows: median age 67 years (range, 43-83), male 40 (61%), Pancreatoduodenectomy / Distal / Total pancreatectomy 50/14/2, combined portal vein or superior mesenteric vein resection 25 (38%), no postoperative complication 25 (38%), Well/Moderately/Poorly differentiated type 23/41/2, the median tumor size 30mm (range, 13-130), the median number of dissected LN 25 (range, 10-60), the median number of positive LN 2 (range, 0-8), and the resection margin status (R0/1) 62/4. The distribution in the 8 th edition (1A/1B/2A/2B/3) was 6(9%) / 10(15%) / 5(8%) / 36(54%) / 9(14%), respectively. 2-year overall survival (OS) and relapse-free survival (RFS) were 70% and 52%. In the 8 th edition staging system (1A/1B/2A/2B/3), 2-year OS and RFS were 100/90/80/66/40% and 83/70/53/49/22%, respectively. 2-year OS and RFS by T classification according to AJCC 8 th edition were 100/68/56% and 90/39/56% (T1/2/3), while those by N classification were 90/66/40% and 70/49/22% (N0/1/2), respectively. Conclusions: The survival was poor with progress of the stage in the new classification. Especially at N stage, it might be suggested an association with prognosis.
Randomized, multicentre phase II trial of the sequencing of radium-223 and docetaxel plus prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC).
Authors: Vincenza Conteduca, Stefano Severi, Stefania Gori, Luca Galli, Michele Aieta, Gaetano Facchini, Cristina Masini, Donatello Gasparro, Lucia Fratino, Susanne Baier, Emanuela Scarpi, Sara Testoni, Valeria Sirna, Linda Valmorri, Bernadette Vertogen, Giovanni Paganelli, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2018)

TPS396 Background: Currently, the challenge is to reach a consensus on the best way to sequence different therapies for mCRPC patients (pts) in terms of efficacy and tolerability. Radium223 is a novel survival-prolonging targeted-α-therapy, but timing of its use in the treatment sequence of mCRPC remains an unanswered question, given the wide availability of therapeutic options Methods: This is a prospective, multicenter, randomized phase II study in symptomatic bone-only mCRPC pts who progressed after any androgen deprivation therapy, abiraterone and/or enzalutamide. Pts will be randomized 1:1 to receive radium223 initially followed by docetaxel+prednisone at the time of progression, or docetaxel+prednisone initially followed by radium223 at progression. In both treatment arms, the second step will be optional according to clinical evolution of disease (clinical deterioration and/or development of visceral metastases); however, each patient that will not enter in the second step will be still evaluable for the objectives of the study. No stratification factor will be used for randomization. Primary endpoint is to determine the better tolerated sequencing between radium223 and docetaxel in terms of health-related quality of life after completing the sequence and separately after each treatment. Based on primary endpoint, considering a type I error 0.1, type II error 0.2, proportion of responder pts in the standard arm 0.1 and in the experimental arm of 0.4, and assuming 10% loss to follow-up, a total of 70pts (35 for each arm) will be enrolled in the study. The study duration will be 36months; 15months of accrual, and 1 year of follow-up on the last participant enrolled. Secondary endpoints are to compare overall/progression-free/total progression free survival in pts treated with sequential therapy between radium223 and docetaxel. Additional secondary objective is to identify predictive factors for radium223 therapy, including potential circulating biomarkers through the plasma collection from all enrolled pts at different timepoints and the early prognostic role of functional imaging, such as PET with choline and/or PSMA. Clinical trial information: NCT03230734.
Impact of USPSTF recommendations on utilization of PSA screening in Medicare beneficiaries.
Authors: Rahul Ramesh Khairnar, Mark Mishra, Ebere Onukwugha
Journal: Journal of Clinical Oncology (2018)

166 Background: Previous studies assessing the impact of the United States Preventive Services Task Force (USPSTF) recommendations on utilization of prostate-specific antigen (PSA) screening have not investigated longer-term impacts of the 2008 recommendations nor have they investigated the impact of the 2012 recommendations in the Medicare population. The study aim was to evaluate change in utilization of PSA screening, post USPSTF recommendations of 2008 and 2012, and to assess trends and determinants of receipt of PSA screening in the Medicare population. Methods: This retrospective study of male Medicare beneficiaries utilized Medicare Current Beneficiary Survey (MCBS) data and linked administrative claims from 2006-2013. Beneficiaries aged ≥65 years, with continuous enrollment in Parts A and B for each year they were surveyed were included in the study cohort. Beneficiaries with self-reported or claims-based diagnosis of prostate cancer were excluded. Beneficiaries with Medicare eligibility due to end stage renal disease or disability were also excluded. The primary outcome was receipt of PSA screening. Other measures include age groups (65-74 and ≥75), time periods (pre- and post-2008 and 2012 recommendations), and sociodemographic variables. Results: The study cohort consisted of 11,028 beneficiaries, who were predominantly white (87.56%), married (69.25%), and unemployed (84.4%); 52.21% beneficiaries were aged ≥75. Declining utilization trends for PSA screening were observed only in men aged ≥75 after 2008 recommendations and in both age groups after 2012 recommendations. The odds of receiving PSA screening declined by 17% percent in men aged ≥75 after the 2008 recommendations and by 29% in men aged ≥65 after the 2012 recommendations. Conclusions: The USPSTF recommendations of 2008 and 2012 against PSA screening were associated with declines in utilization of PSA screening during the study period. USPSTF recommendations play a significant role in affecting utilization patterns of health services. Future studies should evaluate if the proposed 2017 update to these recommendations advocating shared decision-making for PSA screening in men aged 55-69 increase utilization in this age-group.
Prognosis of hospitalized patients with community-acquired pneumonia
Authors: F. Tokgoz Akyil, M. Yalcinsoy, A. Hazar, A. Cilli, B. Celenk, O. Kilic, A. Sayiner, N. Kokturk, A. Sakar Coskun, A. Filiz, E. Cakir Edis
Journal: Pulmonology (2018)

The long-term prognosis of patients with community-acquired pneumonia (CAP) has attracted increasing interest in recent years. The objective of the present study is to investigate the short and long-term outcomes in hospitalized patients with CAP and to identify the predictive factors associated with mortality. The study was designed as a retrospective, multicenter, observational study. Hospitalized patients with CAP, as recorded in the pneumonia database of the Turkish Thoracic Society between 2011 and 2013, were included. Short-term mortality was defined as 30-day mortality and long-term mortality was assessed from those who survived 30 days. Predictive factors for short- and long-term mortality were analyzed. The study included 785 patients, 68% of whom were male and the mean age was 67 ± 16 (18–92). The median duration of follow-up was 61.2 ± 11.8 (37–90) months. Thirty-day mortality was 9.2% and the median survival of patients surviving 30 days was 62.8 ± 4.4 months. Multivariate analysis revealed that advanced age, the absence of fever, a higher Charlson comorbidity score, higher blood urea nitrogen (BUN)/albumin ratios and lower alanine aminotransferase (ALT) levels were all predictors of long-term mortality. Long-term mortality following hospitalization for CAP is high. Charlson score and lack of fever are potential indicators for decreased long-term survival. As novel parameters, baseline BUN/albumin ratios and ALT levels are significantly associated with late mortality. Further interventions and closer monitoring are necessary for such subgroups of patients.
Gauging public awareness and interest related to pancreatic cancer: An analysis of Google search volumes.
Authors: Dhruvika Mukhija, Alok A. Khorana, Davendra Sohal
Journal: Journal of Clinical Oncology (2018)

250 Background: Over the last 2 decades, the internet has become a major source of medical information. Infoveillance, i.e., public health surveillance using online content analysis has become a powerful tool and internet search activity has been used as a surrogate to gauge public awareness and interest for particular diseases. We aimed to evaluate the search volume for pancreatic cancer (PC), using colon cancer (CC), as a comparator, using data from a popular search engine. Methods: Using Google Trends, a public web facility of Google Inc., based on Google Search, we compared the relative frequency of search terms ‘pancreatic cancer’ and ‘colon cancer’ between 1st January 2004 and 31st August 2017 (n = 164 months). The program assigns a reference value of 100 for the point of maximum popularity from among all the search terms during the search period and provides comparative monthly scores, which we termed relative interest scores (RIS). The RIS for each cancer was then adjusted for incidence (i.e., 53,070 for PC and 95,270 for CC, based on 2016 data), calculated per 10,000 patients and termed ‘i-RIS’. A p-value of &lt; 0.05 was considered significant. Results: For the entire duration, the maximum popularity (RIS = 100) corresponded to a point in March 2008 for PC, likely related to the diagnosis of a famous celebrity during that month. Similar but smaller surges in RIS were observed for other significant news events related to PC during other months (January 2009, October 2009 and October 2011). Overall, the mean (±S.D) RIS for PC and CC were 32.52±8.98 and 50.18±6.44, respectively (p &lt; 0.001). However, the i-RIS was somewhat higher for PC (6.12±1.69) as compared with CC (5.26±0.67) (p &lt; 0.001). Conclusions: Internet search data can provide estimates of public awareness and interest related to cancer. For PC, incidence-adjusted search volumes show spikes in search volumes related to major news events, providing internal validation of these results. Generating news items and promotion by celebrities may play a significant role in the success of cancer awareness campaigns.
Commentary: Palliative care and assisted dying are not mutually exclusive
Authors: Bobbie Farsides
Journal: BMJ (2018)

Two decades ago, I argued that it was logically consistent to be a good palliative care doctor and to think that for some patients the best option would be a managed death.1

In working with practitioners, policy makers, and fellow academics committed to improving the care of dying patients, my observation was that orthodox top-down pronouncements on the idea of assisted dying were the norm, often with no dissent, challenge, or even examination.

I made no claims about whether it was time for change. Instead I wanted to challenge the silence around a question that health professionals were to a large degree avoiding.

This article led me to the eye of a storm I couldn’t have anticipated, with influential people calling for my …
PERCUTANEOUS TRANSLUMINAL PULMONARY ANGIOPLASTY IN INOPERABLE CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Li Wen, Wuwan Wang, Zhengdong Song, Wenhai Shi, Panpan Feng, Xiang Rui, Wei Huang
Journal: Journal of the American College of Cardiology (2018)
CONTINUOUS HOME INTRAVENOUS INOTROPIC THERAPY DECREASES SYMPTOM SEVERITY AND MAY REDUCE HOSPITALIZATIONS IN PATIENTS WITH ADVANCED HEART FAILURE
Authors: Allyson Checkley, Samantha Kile, Loretta Kristofek, Danielle Brunjes, William Bolgar, Vinay Thohan, MaryJane Farr, Jonathan Rich
Journal: Journal of the American College of Cardiology (2018)