tbuckley/cabot-search huggingface dataset:
Phase II study of regorafenib (Reg) in patients with previously treated advanced pancreatic cancer (APC).
Authors: John Stuart Salmon, Jimmy J. Hwang, Myra M. Robinson, James Thomas Symanowski, Lloye M Dillon, Lopamudra Das Roy, Matthew A. Beldner, Kelry Preston, Sharon Buige, Reza Nazemzadeh, Pinku Mukherjee, Farhang Farhangfar, Edward S. Kim
Journal: Journal of Clinical Oncology (2017)

e15751 Background: APC that has progressed after treatment with gemcitabine has a dismal prognosis and novel treatment approaches are needed. Reg is a potent oral inhibitor of VEGFR 1-3, PDGFR, TIE-2, FGFR-1, KIT, and the RAF kinases, and has activity in pancreatic xenograft models. We tested the activity of Reg in patients (pts) with refractory APC. Methods: This single arm, single center phase II study evaluated Reg (120mg/d, for 21 days, followed by 7-day break, with escalation to 160mg after the 1st cycle if tolerated) in pts with metastatic pancreatic cancer whose disease had progressed after at least one prior line of therapy and treatment with gemcitabine. Pts underwent radiographic evaluation every 2 cycles. The primary endpoint was 16-wk PFS. Kaplan Meier techniques were used to estimate PFS and OS. Serum tumor MUC1 antigen (tMUC1) concentrations were measured at baseline, end of cycle 1, and off-treatment using the TAB 004 antibody (Agkura Personal Score blood test, OncoTAb, Inc). Relative change of tMUC1 from baseline to end of cycle 1 was compared between those with and without 16-wk disease control. Results: 20 pts were enrolled into the study. Median age = 65 (47-79), and 80% (16/20) had 2 or more prior lines of therapy for advanced disease. Landmark 16 wk PFS = 10% (2/20), crossing a predefined futility boundary to demonstrate 20% improvement over historical controls with BSC. ORR was 5% (1/20), and DCR at 8 wks was 20% (4/20). Median PFS was 6.1 wks (95% CI: 2.9 – 7.1), and median OS was 9.4 wks (95% CI: 8.1 – 17.0). 10% of pts (2/20) had protocol defined Reg dose escalation to 160mg, and 30% (6/20) had dose reduction to 80mg. The most frequent grade 3-4 adverse events included hyponatremia (35%), fatigue (20%), and hypoalbuminemia (20%). Baseline tMUC1 varied substantially, mean 69.6ug/mL, median 51.3ug/mL (10.8 – 310.5). Serum tMUC1 decreased by a mean of 20.8% in the pts with disease control at 16 wks (n = 2), but increased by 65% (mean) in pts with disease progression or death within 16 wks (n = 13, p = 0.048). Conclusions: Reg has minimal activity as a single agent in pts with heavily treated APC. Serum tMUC1 levels measured by TAB 004 antibody may be a novel tumor marker in this disease. Different treatment approaches are needed. Clinical trial information: NCT02080260.
Advanced life support in obstetrics
Authors: Rajani Tyagi
Journal: BMJ (2007)

FURTHER INFORMATION 

ALSO, Unit 16 St Peter's Wharf, Newcastle upon Tyne NE6 1TZ; tel 0191 276 5738, fax 0191 265 3119; www.also.org.uk

Advanced life support in obstetrics (ALSO) courses run in the United Kingdom and internationally. The ALSO training programme is owned by the American Academy of Family Physicians and there are three types of course available—a provider course needs to be taken initially; an instructor course can be done by those who have passed the provider course and who have been recommended; and a refresher course to be done every three years in …
A cost-benefit analysis for sonographic screening for renal tumors.
Authors: Shmuel Roizman, Moshe Leshno, Miki Haifler, Yishai Hode Rappaport, Amnon Zisman
Journal: Journal of Clinical Oncology (2018)

665 Background: In the last 2 decades, the rates of metastatic Renal Cell Carcinoma (RCC) at diagnosis declined from 33% to 17%This fact is attributed to massive penetration of cross sectional imaging leading to a marked stage migration. The cost of targeted therapy for metastatic RCC patients is very high. These trends led us to hypothesize that screening for RCC with ultrasound may be cost effective. Objective: To assess the cost effectiveness of screening with ultrasound for renal tumors in the general population over 60 years of age. Methods: Using the Markov model, a mathematical framework was set up describing the course of disease with and without screening for RCC using abdominal ultrasonography. Quality Adjusted Life Year (QALY) and financial costs were the outputs of the model. Results: Average costs for the screening strategy was 137.4 U$ and for non-screening was 31.4 U$. Screening and non-screening strategy would add an average of 21.7396 and 21.7385 QALY, respectively. An increase of 0.001 QALY equates to Incremental Cost Effectiveness Ratio (ICER) of 86,4 U$ per QALY, Currently, the cost which is considered cost effective for 1 QALY point is approximately 27,548.21 U$. The two variables most influential on the model output were prevalence of RCC and US cost. Conclusions: To our knowledge, this is the sole cost benefit screening study performed for RCC in the targeted therapy era. Screening for renal tumors using abdominal ultrasonography at a cost of 35.81 U$ per exam is cost effective. Our findings are highly suggestive that early screening for RCC may be cost effective for preventing RCC metastatic disease and nevertheless will save lives.
Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone-metastatic prostate cancer.
Authors: Jinge Zhao, Guangxi Sun, Banghua Liao, Xingming Zhang, Pengfei Shen, Junru Chen, Jiandong Liu, Hao Zeng
Journal: Journal of Clinical Oncology (2018)

336 Background: Treatments for de novo metastatic prostate cancer (mPCa) are evolving. However predictive models for this subset of the population are still lacking. The aim of this study is to develop nomograms to predict the incidence of castration resistant PCa (CRPC) and overall survival (OS) for de novo mPCa patients. Methods: Data from 449 de novo mPCa patients were retrospectively analyzed. Patients were randomly divided into either the training or the validation cohort. Predictive factors were selected by Cox-proportional model and further used for building predictive models. The outcomes were incidence of CRPC and OS. Results: Predictive parameters included: Gleason Score (GS), intraductal carcinoma of the prostate (IDC-P), ECOG status, alkaline phosphatase (ALP), hemoglobin (HGB) and prostate specific antigen (PSA). IDC-P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated C-index of 0.762 and 0.723, respectively. Based on the beta-coefficients of the final model, risk classification systems were constructed. For those with favorable-, intermediate- and poor-prognosis, the median time to CRPC was 62.6, 28.0 and 13.0 months (P&lt;0.001), and the median OS was not reached, 55.0 and 33.0 months, respectively (P&lt;0.001). Conclusions: We developed two novel nomograms to predict the incidence of CRPC and OS for de novo mPCa patients. These tools may assist physicians’ decision-making and design of clinical trials.
COST-EFFECTIVENESS OF EXTENDED AND ONE-TIME SCREENING FOR ATRIAL FIBRILLATION VERSUS NO SCREENING IN THE UNITED STATES
Authors: Gail D. Wygant, Mustafa Oguz, Tereza Lanitis, Robert Leipold, Keith Friend, Soeren Mattke, Daniel Singer, Andreas Nikolaou, Patrick Hlavacek, Shawn Li
Journal: Journal of the American College of Cardiology (2018)
Effect of surgical resection on survival following neoadjuvant chemotherapy in patients with stage I-II pancreatic adenocarcinoma.
Authors: Ryan James Henrix, Eva Rouanet, Kurt Schultz, Tasneem Ali, Bradley Alan Switzer, Venu Gopal Bathini, Giles Francis Whalen, Jennifer Lafemina
Journal: Journal of Clinical Oncology (2018)

255 Background: Pancreatic adenocarcinoma (PDAC) is a lethal malignancy, representing the 4th leading cause of cancer deaths. Our 2011 institutional protocol guides that patients with Stage I/II PDAC receive neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine- nab-paclitaxel); a similar protocol is followed with patients with Stage III disease. The aim of the study is to determine if potentially curative surgery provides added survival benefit, compared to neoadjuvant chemotherapy alone. Methods: Patients who received neoadjuvant chemotherapy and who were diagnosed with stage I-III PDAC from 2011-2017 at a tertiary medical center were included in this prospectively-collected, retrospective analysis. The primary endpoint was overall survival (OS). Kaplan-Meier curves are compared using Log-rank. Cox proportional hazards were used to adjust for confounders. Results: 105 patients met inclusion criteria: 38 (36%) had Stage I disease (n = 18 had neoadjuvant chemotherapy and surgery [N+S], n = 20 had neoadjuvant chemotherapy [N] alone), 44 (42%) had stage II (N+S n = 20, N n = 24), 23 (22%) had stage III (N+S n = 4, N n = 19). There was no difference in 5-year OS regardless of treatment regimen in patients with Stage I (median OS N+S 22.5 mo vs N 27.9 mo; p = 0.99, HR 1.00, 95%CI 0.74-1.35) or Stage II disease (median OS N+S 28.7 mo vs N 27.6 mo; p = 0.69; HR 1.06, 95%CI 0.79-1.41). There is a trend towards improved OS with N+S in those with Stage III disease (median OS N+S 46.0 mo vs N 14.5 mo, p = 0.08), but the number who underwent resection is low (17%), limiting this analysis. Conclusions: In patients with Stage I-II PDAC, potentially curative surgery may not provide additional survival benefit beyond that afforded by modern day neoadjuvant chemotherapy. Stage III outcomes are limited by small numbers, and the impact of surgery is unclear. It may be possible that the locally unresectable tumor that is rendered resectable with neoadjuvant chemotherapy may be associated with a more favorable biology, such that surgery offers added survival benefit. Additional large-scale trials are needed to confirm whether newer therapies may obviate the need for resection in select patients.
EMPAGLIFLOZIN INDUCES A MYOCARDIAL METABOLIC SHIFT FROM GLUCOSE CONSUMPTION TO KETONE METABOLISM THAT MITIGATES ADVERSE CARDIAC REMODELING AND IMPROVES MYOCARDIAL CONTRACTILITY
Authors: Carlos G. Santos-Gallego, Juan Antonio Requena Ibanez, Rodolfo San Antonio, Kiyotake Ishikawa, Shin Watanabe, Maria Belen Picatoste Botija, Angel Javier Sanz Salvo, Roger Hajjar, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2018)
The Scintigraphic Drooping Lily Sign
Authors: Karine Sahakyan, Melissa R. Spevak, Harvey A. Ziessman, Michael A. Gorin, Steven P. Rowe
Journal: Clinical Nuclear Medicine (2018)

Abstract The “drooping lily” sign is identified on intravenous urography or voiding cystourethrography in patients with a duplicated renal collecting system and refers to inferolateral displacement of a functioning lower pole moiety by an obstructed upper pole collecting system. In this case, a 2-month-old girl with a prenatal diagnosis of hydronephrosis was found to have a “scintigraphic drooping lily” sign on 99m Tc-dimercaptosuccinic acid renal scan. Evaluation with ultrasound and voiding cystourethrography confirmed a duplicated collecting system and obstructed upper pole moiety. Correlation with anatomic imaging can help avoid mistaking the scintigraphic “drooped” lower pole for an inferiorly positioned normal kidney.
Tau in Chronic Traumatic Encephalopathy
Authors: Damir Janigro
Journal: JAMA Neurology (2018)

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Facial Neutrophilic Dermatosis Mimicking Iododerma and Associated With Inflammatory Bowel Disease
Authors: Natalie H. Matthews, Vivian Wong, Leslie Robinson-Bostom, Newsha Lajevardi
Journal: JAMA Dermatology (2018)

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Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
Authors: Kyung-Ah Lee, Kyu-Chan Cho, Boram Kim, In-Hwan Jang, Kibum Nam, Young Eun Kwon, Myungjin Kim, Do Young Hyeon, Daehee Hwang, Jae-Hong Seol, Won-Jae Lee
Journal: Cell Host & Microbe (2018)
Medical academics reject plans to move GMC registration to time of graduation
Authors: Abi Rimmer
Journal: BMJ (2014)

Medical academics have strongly opposed plans to move the point of registration with the General Medical Council to graduation from medical school.

The plans were first proposed by the UK wide Shape of Training review, led by David Greenaway, vice chancellor of Nottingham University, and have been supported by Health Education England.1

Delegates at the BMA’s conference of medical academic representatives in London last week supported a motion that “strongly” opposed the move. The motion …
PLATELET TOLL LIKE RECEPTOR AND ITS LIGAND HIGH MOBILITY GROUP BOX 1 EXPRESSION IS INCREASED IN THE LEFT ATRIUM OF AF PATIENTS
Authors: Kadri M. Gurses, Duygu Kocyigit, Muhammed Ulvi Yalcin, Hande Canpinar, Banu Evranos, Ugur Canpolat, Hikmet Yorgun, Mehmet Levent Sahiner, Dicle Guc, Kudret Aytemir
Journal: Journal of the American College of Cardiology (2018)
MSc in geriatric medicine
Authors: Anil Kumar, Elliot Epstein
Journal: BMJ (2006)

This MSc is geared for medical and non-medical practitioners. It is designed to meet the needs of doctors and other allied health professionals who wish to become experts in the health of older people. The course is designed to help students to develop critical awareness of the health needs of older people and also to improve their understanding of the manner in which services are developed and delivered.

The West Midlands Deanery encourages specialist registrars in geriatric medicine to take this course as part of their training.

I enjoy the day to day practice of geriatric medicine but I felt …
Nonmalignant late cutaneous changes after allogeneic hematopoietic stem cell transplant in children
Authors: Jennifer T. Huang, Johanna S. Song, Elena B. Hawryluk, Wendy B. London, Dongjing Guo, Madhumitha Sridharan, David E. Fisher, Leslie E. Lehmann, Christine N. Duncan
Journal: Journal of the American Academy of Dermatology (2018)
A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5
Authors: Brian S. White, Irena Lanc, Julie O’Neal, Harshath Gupta, Robert S. Fulton, Heather Schmidt, Catrina Fronick, Edward A. Belter, Mark Fiala, Justin King, Greg J. Ahmann, Mary DeRome, Elaine R. Mardis, Ravi Vij, John F. DiPersio, Joan Levy, Daniel Auclair, Michael H. Tomasson
Journal: Blood Cancer Journal (2018)

Abstract Multiple myeloma (MM) is a disease of copy number variants (CNVs), chromosomal translocations, and single-nucleotide variants (SNVs). To enable integrative studies across these diverse mutation types, we developed a capture-based sequencing platform to detect their occurrence in 465 genes altered in MM and used it to sequence 95 primary tumor-normal pairs to a mean depth of 104×. We detected cases of hyperdiploidy (23%), deletions of 1p (8%), 6q (21%), 8p (17%), 14q (16%), 16q (22%), and 17p (4%), and amplification of 1q (19%). We also detected IGH and MYC translocations near expected frequencies and non-silent SNVs in NRAS (24%), KRAS (21%), FAM46C (17%), TP53 (9%), DIS3 (9%), and BRAF (3%). We discovered frequent mutations in IGLL5 (18%) that were mutually exclusive of RAS mutations and associated with increased risk of disease progression ( p = 0.03), suggesting that IGLL5 may be a stratifying biomarker. We identified novel IGLL5 / IGH translocations in two samples. We subjected 15 of the pairs to ultra-deep sequencing (1259×) and found that although depth correlated with number of mutations detected ( p = 0.001), depth past ~300× added little. The platform provides cost-effective genomic analysis for research and may be useful in individualizing treatment decisions in clinical settings.
Opioid prescriptions rise in England despite poor efficacy and harms, finds study
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The number of opioid drugs prescribed in England is steadily rising despite a lack of effectiveness for treating chronic pain and their potentially serious side effects, a study has found.1

Researchers also found that opioid prescriptions by GPs are higher in deprived areas and northern England.

The retrospective observational study, led by Luke Mordecai, a pain research fellow at University College London Hospital, examined official government data on opioids prescribed in primary practice in England from August 2010 to February …
Knee pain after a fall
Authors: Abhiram R Bhashyam, Michael J Weaver
Journal: BMJ (2018)

A 69 year old man slipped in the snow and presented with swelling and pain in the left knee. On examination, he could not extend his knee and had a palpable, visible indentation on the surface of his distal anterior thigh, above the patella. It was not an open injury and he did not have substantial tension in the overlying skin. There was no neurovascular deficit. A radiograph was obtained (fig 1). What is the diagnosis?



Fig 1 
Lateral radiograph of the left knee



Intra-articular patella dislocation with quadriceps tendon rupture.

### Discussion

The lateral radiograph of the knee shows that the left patella has dislocated around its horizontal axis and its articular surface is facing inferiorly. The upper pole of the patella is engaged in the intercondylar groove of the femur. The …
Upfront docetaxel with androgen deprivation therapy in the elderly patient with metastatic hormone-naïve prostate cancer: Single institution experience.
Authors: Lindsay Jennifer Andrew Rayner, Amarnath Challapalli, Eve Blackmore, Katherine Rea, Natasha Wells, Paul White, Serena Hilman, Susan Masson, Rebecca Huckett, Krishna Garadi, Hannah Kirk, Julian Kabala, Viktoria Oikonomopoulou, Amit Bahl
Journal: Journal of Clinical Oncology (2018)

328 Background: Following CHAARTED &amp; STAMPEDE, upfront Docetaxel chemotherapy became standard of care for metastatic hormone-naïve prostate cancer (mHNPC). We sought to evaluate our experience in the elderly group of patients (&gt;70 yrs) compared with the non-elderly cohort. Methods: A retrospective analysis was undertaken of 38 patients commenced on upfront docetaxel chemotherapy, from Jan 16 - Jan 17. Patients were stratified as low (LR) and high risk (HR), as per the LATITUDE study. Progression was defined as per PCWG-3 criteria. The progression free survival (PFS) was calculated as time from start of treatment to date of progression and analysed by Kaplan-Meier estimates and log-rank test. Rates of febrile neutropenia (FN) were also evaluated. Results: The median age was 69 (range: 53-80) yrs, with 50% (19/38) HR patients. The median PFS was 11.5m for progressors (P; 42%) and not reached for non-progressors (NP; 58%), (p&lt;0.0001). Granulocyte colony stimulating factor (G-CSF) was used in 13/38 (34%) patients; these did not experience FN. The overall rate of FN was 20% where G-CSF was not used. Overall 31/38 (81.6%) completed 6 cycles of chemotherapy, with 26% requiring dose reductions (Table). Overall, of the 9/16 (56.3%) patients who progressed within 6m of completing docetaxel, 3 had Cabazitaxel as the next treatment (P: 2/3 (66.7%), median PFS 6.2m) and 6 had novel androgen receptor targeted therapy (P: 5/6 (83.3%), median PFS 3.3m). Conclusions: Upfront docetaxel is reasonably well tolerated in the elderly with comparable median PFS to younger patients. Use of GCSF significantly minimizes the risk of FN in this group and should be considered as standard of care. In patients who progress within 6m of completing docetaxel, we feel optimal sequencing to be Cabazitaxel followed by subsequent therapies.[Table: see text]
Talks on professional standards for medical managers to begin within months
Authors: Matthew Limb
Journal: BMJ (2014)

Talks that could lead to medical managers being formally assessed against a set of professional standards are due to start over the coming months, the Faculty of Medical Leadership and Management has said.

Representative groups for medical leaders and managers are to consider how to “professionalise” medical management careers and strengthen support and development for those taking up the roles, which it is hoped may boost recruitment.

The Faculty of Medical Leadership and Management, a professional membership association, will consult stakeholders and members on many …
ILIAC ARTERY OCCLUSION IN A PATIENT WITH ALLOGRAFT RENAL TRANSPLANT CAUSING REFRACTORY HEART FAILURE AND SIMULATING RENAL ARTERY STENOSIS WITH SOLITARY KIDNEY
Authors: Hetavi Mahida, Nene Ugoeke, Obiora Maludum, Bharatsinh Gharia, Renato Apolito
Journal: Journal of the American College of Cardiology (2018)
RELIABILITY OF CARDIAC FAT VOLUMES MEASURED BY NON-CONTRAST CORONARY CALCIUM COMPUTED TOMOGRAPHY USING A SEMI-AUTOMATED CARDIAC FAT ANALYSIS SOFTWARE
Authors: Eranthi Jayawardena, Dong Li, Christopher Dailing, Rine Nakanishi, Damini Dey, Assad Qureshi, Brooke Dickens, Nicolai Hathiramani, Michael Kim, Ferdinand Flores, Ann E. Kearns, Matthew Budoff
Journal: Journal of the American College of Cardiology (2018)
METABOLOMICS PROFILING OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN WOMEN WITH, OR AT RISK FOR HIV INFECTION: THE WOMEN'S INTERAGENCY HIV STUDY
Authors: Claudio Bravo, Simin Hua, Clary B. Clish, Justin Scott, Amy Deik, Robert C. Kaplan, Jason Lazar, Kathryn Anastos, Octavio A. Robles, Jorge Kizer, Qibin Qi
Journal: Journal of the American College of Cardiology (2018)
Associations Among Mucosal and Transmural Healing and Fecal Level of Calprotectin in Children With Crohn’s Disease
Authors: Inbar Weinstein-Nakar, Gili Focht, Peter Church, Thomas D. Walters, Guila Abitbol, Sudha Anupindi, Laureline Berteloot, Jessie M. Hulst, Frank Ruemmele, Daniel A. Lemberg, Steven T. Leach, Ruth Cytter, Mary-Louise Greer, Anne M. Griffiths, Dan Turner
Journal: Clinical Gastroenterology and Hepatology (2018)
Bph6 encodes an exocyst-localized protein and confers broad resistance to planthoppers in rice
Authors: Jianping Guo, Chunxue Xu, Di Wu, Yan Zhao, Yongfu Qiu, Xiaoxiao Wang, Yidan Ouyang, Baodong Cai, Xin Liu, Shengli Jing, Xinxin Shangguan, Huiying Wang, Yinhua Ma, Liang Hu, Yan Wu, Shaojie Shi, Wenliang Wang, Lili Zhu, Xun Xu, Rongzhi Chen, Yuqi Feng, Bo Du, Guangcun He
Journal: Nature Genetics (2018)