tbuckley/cabot-search huggingface dataset:
PTH-090 Monitoring unplanned care and surgical events for crohn’s disease patients treated with biologics in england: linkage of routine administrative data and uk ibd registry
Authors: M Shawihdi, R Driscoll, S Bloom, F Cummings, S Grainger, M Johnson, M Pearson, K Bodger
Journal: Gut (2017)

Introduction  The UK IBD Registry (UK-IBD-R) is developing analyses of Hospital Episode Statistics (HES) with linkage to locally-recorded registry data to generate aggregated reports and indicators to support IBD services. We have created methods to categorise relevant hospital events and track outcomes in HES. For this project, we produced metrics of unplanned care and surgical events before and after initiation of biologics, generating a national scale analysis from HES alone and a proof-of-concept study with linkage to UK-IBD-R.  Method   Datasets:  HES for England (04/05 to 13/14); UK-IBD-R dataset (to June 2016).  Patient  cohorts : (1)  HES cohort  identified using HES only. We flagged all admissions (incl. daycases) with a diagnosis of CD and procedure code X921 (biologic infusion; assumed to be infliximab), locating 1 st infusion for each case; (2)  Registry cohort  was based on anonymized linkage (undertaken by NHS Digital), identifying cases with a registry-recorded diagnosis of CD, a medication entry for anti-TNF drug (infliximab, inflectra or adalimumab) and a valid start date.  Hospital events in HES:  All-cause episodes were extracted for 1 year before ( Yr-Pre ) and after ( Yr-Post ) start of treatment, categorising each inpatient and daycase event based on admission method, diagnoses (IBD-specific, IBD-related and Other) and procedures.  Results   HES cohort:  n=15 399 (Age: 35 [16]; 47% male);  Registry cohort:  n=217 (Age: 26 [13.5]; 56% male). Unplanned care activity for Yr-Pre versus Yr-Post are shown in Abstract PTH090 Figure 1, confirming substantial reductions in all-cause and CD-specific emergency care following initiation of biologics in routine UK practice (p 71% ) continued infusion visits beyond induction phase (’Maintenance’), and 4522 ( 29% ) did not (’Stopped’).  Surgical resections at 1 year:  Total, 944 (6.2%); Maintenance versus Stopped: 395 (3.6%) v. 549 (12%), p Emergency admissions with ‘infections’ at 1  year: Total, 222 (1.4%); Maintenance versus Stopped: 146 (1.3%) v. 76 (1.7%), p=0.11.  Conclusion  These national scale data provide new insights into activity, costs and outcomes associated with routine use of biologics for CD in England. Linkage between UK-IBD-R and HES provides a potentially powerful tool for monitoring of activity, process and outcome of IBD care. The use of existing datasets reduces the burden of local point-of-care data collection, allowing focus on collecting items to enhance accuracy and clinical depth of analyses. [Funding: Crohn’s and Colitis UK]  Disclosure of Interest  None Declared
Senescence after growth arrest: A mechanism by which CDK4/6 inhibitors can mediate their activity suppressing tumor progression
Authors: A. Koff, M.E. Klein, M.A. Dickson, C. Antonescu, L.-X. Qin, S.J. Dooley, G. Schwartz, A.M. Crago, S. Singer, W.D. Tap
Journal: Annals of Oncology (2018)
Breathprinting and Early Diagnosis of Lung Cancer
Authors: Gaetano Rocco, Giorgio Pennazza, Marco Santonico, Filippo Longo, Raffaele Rocco, Pierfilippo Crucitti, Raffaele Antonelli Incalzi
Journal: Journal of Thoracic Oncology (2018)

The electronic nose (e-nose) is a promising technology as a useful addition to the currently available modalities to achieve lung cancer diagnosis. The e-nose can assess the volatile organic compounds detected in the breath and derived from the cellular metabolism. Volatile organic compounds can be analyzed to identify the individual chemical elements as well as their pattern of expression to reproduce a sensorial combination similar to a fingerprint (breathprint). The e-nose can be used alone, mimicking the combinatorial selectivity of the human olfactory system, or as part of a multisensorial platform. This review analyzes the progress made by investigators interested in this technology as well as the perspectives for its future utilization.
Concurrent Veliparib With Chest Wall and Nodal Radiotherapy in Patients With Inflammatory or Locoregionally Recurrent Breast Cancer: The TBCRC 024 Phase I Multicenter Study
Authors: Reshma Jagsi, Kent A. Griffith, Jennifer R. Bellon, Wendy A. Woodward, Janet K. Horton, Alice Ho, Felix Y. Feng, Corey Speers, Beth Overmoyer, Michael Sabel, Anne F. Schott, Lori Pierce
Journal: Journal of Clinical Oncology (2018)

Purpose Locoregional control for inflammatory breast cancers and chest wall recurrences is suboptimal, which has motivated interest in radiosensitization to intensify therapy. Preclinical studies have suggested a favorable therapeutic index when poly (ADP-ribose) polymerase inhibitors are used as radiosensitizers; clinical investigation is necessary to establish appropriate dosing and confirm safety. Patients and Methods We conducted a multi-institutional phase I study of veliparib and concurrent radiotherapy (RT) to the chest wall and regional lymph nodes in 30 patients with inflammatory or locally recurrent breast cancer after complete surgical resection. RT consisted of 50 Gy to the chest wall and regional lymph nodes plus a 10-Gy boost. A Bayesian time-to-event continual reassessment method escalated dose through four levels, with a 30% targeted rate of dose-limiting toxicity (DLT) measured during the 6 weeks of treatment plus 4 weeks of follow-up. DLTs were defined as confluent moist desquamation > 100 cm2, nonhematologic toxicity grade ≥ 3, toxicity that requires an RT dose delay > 1 week, absolute neutrophil count < 1,000/mm3, platelet count < 50,000/mm3, or hemoglobin < 8.0 g/dL if possibly, probably, or definitely related to study treatment. Results Five DLTs occurred: Four were moist desquamation (two each at 100 and 150 mg twice a day), and one was neutropenia (at 200 mg twice a day). The crude rate of any grade 3 toxicity (regardless of attribution) was 10% at year 1, 16.7% at year 2, and 46.7% at year 3. At year 3, six of 15 surviving patients had severe fibrosis in the treatment field. Conclusion Although severe acute toxicity did not exceed 30% even at the highest tested dose, nearly half of surviving patients demonstrated grade 3 adverse events at 3 years, which underscores the importance of long-term monitoring of toxicity in trials of radiosensitizing agents.
Effect of Traditional Heart Failure Risk Factors on Myocardial Dysfunction in Adult Survivors of Childhood Cancer
Authors: Mark T. Nolan, Thomas H. Marwick, Juan Carlos Plana, Zhenghong Li, Kirsten. K. Ness, Vijaya M. Joshi, Daniel M. Green, Leslie L. Robison, Melissa M. Hudson, Gregory T. Armstrong
Journal: JACC. Cardiovascular imaging (2018)
Updated results of MSCMCC gastric cancer cohort: Indirect comparison between adjuvant chemoradiation and perioperative chemotherapy in gastric cancer patients.
Authors: Magdalena Mydlowska, Sebastian Rybski, Zuzanna Guzel, Katarzyna Kokoszyńska, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2018)

123 Background: In the western world gastric cancer patients are either treated with peri-operative chemotherapy or adjuvant chemoradiation and no direct comparisons of these two treatment strategies are available. In our referral gastric cancer center (MSCMCC) we have changed in January 2013 the treatment protocol from adjuvant chemoradiation (like in INT-0116 study) to peri-operative chemotherapy (ECF or CF regimen). Here we report the updated results of single institution indirect comparison of two treatment strategies in the treatment of gastric cancer patients. Methods: 139 consecutive pts who underwent gastrectomy between 2009-2015 treated at MSCMCC were identified in a cohort manner (2009-2012 radiochemotherapy: 60 pts; 2013-2015- peri-operative chemotherapy: 79 pts). The patients’ clinical characteristics were collected from medical records. All patients were followed for relapse and survival with median observation time of 57 and 17 months for chemoradiation and peri-operative chemotherapy respectively. Results: The patients’ characteristics were similar in two groups including, age, sex, ECOG status and Lauren-classification types. DFS was similar in both arms with 47% of patients in radiochemotherapy and 63% of peri-operative chemotherapy patients without relapse at 2 years cut-off (p=0.17). OS was not significantly different between the groups (p=0.783). The toxicity profile was similar in two cohorts, with only leukopenia reported more often in the chemoradiation group (grade 3-4: 43.3% vs 12.3%. p&lt;0.001) and low platelet count (grade 3-4: 6.7% vs 3.7%; p=0.19).There was a trend for excessive mucositis (p=0.067) and diarrhea (p=0.051) in the chemoradiation group. Vomiting more often observed in the peri-operative chemotherapy group (grade 3-4: 29.6% vs 13.3%, p=0.032). Notable, no differences were reported for neutropenia, fatigue and weigth loss. Conclusions: This indirect comparison suggests that results of two modalities are similar in terms of RFS. Further follow up is needed to assess the impact on survival. The toxicity profile favours the peri-operative chemotherapy.
Sixty seconds on . . . diabetes
Authors: Nigel Hawkes
Journal: BMJ (2018)

Is it really? That will come as a surprise to its critics, who said when it was launched in 2015 that it was based on speculation and doubtful assumptions.1

Respectable amounts, certainly: an average of 3.7 kg each if you exclude those who weren’t overweight to start with. NHS England is very pleased …
PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells
Authors: Seong M Kim, Tricia T Nguyen, Archna Ravi, Peter Kubiniok, Brendan T Finicle, Vaishali Jayashankar, Leonel Malacrida, Jue Hou, Jane Robertson, Dong Gao, Jonathan Chernoff, Michelle A Digman, Eric O Potma, Bruce J Tromberg, Pierre Thibault, Aimee L Edinger
Journal: Cancer Discovery (2018)

We report that PTEN-deficient prostate cancer cells use macropinocytosis to survive and proliferate under nutrient stress. PTEN loss increased macropinocytosis only in the context of AMPK activation, revealing a general requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK promotes survival under stress. In prostate cancer cells, albumin uptake did not require macropinocytosis, but necrotic cell debris proved a specific macropinocytic cargo. Isotopic labeling confirmed that macropinocytosed necrotic cell proteins fueled new protein synthesis in prostate cancer cells. Supplementation with necrotic debris, but not albumin, also maintained lipid stores, suggesting that macropinocytosis can supply nutrients other than amino acids. Nontransformed prostatic epithelial cells were not macropinocytic, but patient-derived prostate cancer organoids and xenografts and autochthonous prostate tumors all exhibited constitutive macropinocytosis, and blocking macropinocytosis limited prostate tumor growth. Macropinocytosis of extracellular material by prostate cancer cells is a previously unappreciated tumor-microenvironment interaction that could be targeted therapeutically.Significance: As PTEN-deficient prostate cancer cells proliferate in low-nutrient environments by scavenging necrotic debris and extracellular protein via macropinocytosis, blocking macropinocytosis by inhibiting AMPK, RAC1, or PI3K may have therapeutic value, particularly in necrotic tumors and in combination with therapies that cause nutrient stress. Cancer Discov; 8(7); 866-83. ©2018 AACR.See related commentary by Commisso and Debnath, p. 800This article is highlighted in the In This Issue feature, p. 781.
<i>What is the likely impact of</i> Modernising Medical Careers <i>on the number of posts in the vocational training schemes in the deaneries?</i>
Authors: Anne Hastie
Journal: BMJ (2004)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
BIVALIRUDIN WITH POST-PROCEDURE INFUSION VERSUS HEPARIN WITHOUT GLYCOPROTEIN IIB/IIIA INHIBITORS FOR THE PREVENTION OF STENT THROMBOSIS: A META-ANALYSIS
Authors: Rahman Shah, Abigail Shell, Amina Chaudhry, Asra Butt, Kirstin Hesterberg
Journal: Journal of the American College of Cardiology (2018)
Chronic fractalkine administration improves glucose tolerance and pancreatic endocrine function
Authors: Matthew Riopel, Jong Bae Seo, Gautam K. Bandyopadhyay, Pingping Li, Joshua Wollam, Heekyung Chung, Seung-Ryoung Jung, Anne Murphy, Maria Wilson, Ron de Jong, Sanjay Patel, Deepika Balakrishna, James Bilakovics, Andrea Fanjul, Artur Plonowski, Duk-Su Koh, Christopher J. Larson, Jerrold M. Olefsky, Yun Sok Lee
Journal: Journal of Clinical Investigation (2018)

We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate that chronic administration of a long-acting form of FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated insulin secretion and decreased β cell apoptosis in obese rodent models. Unexpectedly, chronic FKN-Fc administration also led to decreased α cell glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an ERK-dependent mechanism, which triggered β cell action potential (AP) firing and decreased α cell AP amplitude. This results in increased glucose-stimulated insulin secretion and decreased glucagon secretion. Beyond its islet effects, FKN-Fc also exerted peripheral effects to enhance hepatic insulin sensitivity due to inhibition of glucagon action. In hepatocytes, FKN treatment reduced glucagon-stimulated cAMP production and CREB phosphorylation in a pertussis toxin-sensitive manner. Together, these results raise the possibility of use of FKN-based therapy to improve type 2 diabetes by increasing both insulin secretion and insulin sensitivity.
THE RELATIONSHIP BETWEEN LIPOPROTEIN (A), MITRAL ANNULAR CALCIFICATION, AND MITRAL STENOSIS IN A LARGE COHORT OF DYSLIPIDEMIA PATIENTS
Authors: Nishant Shah, Haris Riaz, Risheek Kaul, Antonette Kanishka, Leslie Cho, Haitham Ahmed
Journal: Journal of the American College of Cardiology (2018)
Junior doctors are angry and frustrated by contract proposals, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Junior doctors have been left angry and frustrated by proposals for a new contract, the BMA has said.

Kitty Mohan, co-chair of the BMA’s Junior Doctors Committee, told BMJ Careers that the proposals, which include an extension of standard working hours and “flexible pay premiums,” had made junior doctors very upset. “They feel devalued, they feel frustrated, and they feel like they’re not being listened to,” she said.

“I’ve been involved with the BMA since 2003, and we are seeing levels of frustration, disappointment, and anger that I can’t really remember ever seeing [before],” Mohan added.

Last month the Review Body on Doctors’ …
DISEASE-SPECIFIC QUALITY OF LIFE IMPROVEMENTS DO NOT PREDICT OVERALL QUALITY OF LIFE IN OLDER ADULTS FOLLOWING DISCHARGE FROM HEART FAILURE HOSPITALIZATION
Authors: Jeremy Slivnick, Cara Marolt, Joanna Wells, Erika Trumble, Omar Jimenez, Sergio Teruya, Stephen Helmke, Mathew Maurer, Scott L. Hummel
Journal: Journal of the American College of Cardiology (2018)
Postgraduate and undergraduate medical students may need to be taught differently
Authors: Matthew Limb
Journal: BMJ (2016)

Postgraduate and undergraduate medical students may benefit from different teaching styles, researchers in Australia have found.

A team from Monash University in Melbourne wanted to find out whether graduate entry trainees did better—because of their “greater clinical and life experience”—than undergraduates when studying evidence based medicine.1 The researchers collected data over a five year period (from 2010 to 2014) from 885 trainees. The results were published in …
Fas Promotes T Helper 17 Cell Differentiation and Inhibits T Helper 1 Cell Development by Binding and Sequestering Transcription Factor STAT1
Authors: Gerd Meyer zu Horste, Dariusz Przybylski, Markus A. Schramm, Chao Wang, Alexandra Schnell, Youjin Lee, Raymond Sobel, Aviv Regev, Vijay K. Kuchroo
Journal: Immunity (2018)
ASSOCIATION OF PERIOPERATIVE ANTIPLATELET THERAPY AND OUTCOMES IN PATIENTS WITH DRUG-ELUTING STENT PLACEMENT UNDERGOING NONCARDIAC SURGERY
Authors: Min Ji Kim, Sung-Jin Hong, Jung-Sun Kim, Eun Hwa Kim, Jinae Lee, Chul-Min Ahn, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2018)
Employ more “cheap” physician associates, GPs are told
Authors: Abi Rimmer
Journal: BMJ (2015)

General practices should employ more physician associates because they are cheaper than GPs, a report on the primary care workforce has recommended.1

A report by the Primary Care Workforce Commission said that general practices could benefit from the “wider use of physician associates and healthcare assistants” and that these workers had “significant potential” for primary care to tackle its workload problems.

The commission was established by Health Education England (HEE) at the end of 2014. HEE said that, as …
Internet searches can enhance patients’ consultations with GPs, study finds
Authors: Caroline White
Journal: BMJ (2012)

Patients who use the internet to try to find out what’s wrong with them before seeing their GP can get more out of the consultation, indicates a small study in the British Journal of General Practice that looked at the effect of internet searching.1

Twenty six patients were interviewed for the study, and most believed that undertaking internet searches indicated that they were taking their symptoms and their own health seriously, although most still valued and …
Correction: Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies
Authors: Elizabeth A. Torrone, Charles S. Morrison, Pai-Lien Chen, Cynthia Kwok, Suzanna C. Francis, Richard J. Hayes, Katharine J. Looker, Sheena McCormack, Nuala McGrath, Janneke H. H. M. van de Wijgert, Deborah Watson-Jones, Nicola Low, Sami L. Gottlieb
Journal: PLoS Medicine (2018)

[This corrects the article DOI: 10.1371/journal.pmed.1002511.].
NATIONAL TRENDS IN OUTCOMES OF NON-ST-ELEVATION ACUTE CORONARY SYNDROMES IN ADULTS WITH END-STAGE RENAL DISEASE, 2005-2014
Authors: Bing Yue, Chayakrit Krittanawong, Abel Casso Dominguez, Xin Wei, Mariam Khandaker, Ashish Correa, Shuyang Fang, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Abstract PD8-11: APOBEC3 contributes to mutational load in breast cancer
Authors: W Zhao, Y Peng, GB Mills, G Peng
Journal: Cancer Research (2018)

Abstract Breast cancer results in large part from the accumulation of multiple mutations in premalignant cells, which provide a molecular basis for genetic diversity. This genetic diversity in premalignant cells allows selection for increased proliferation and survival and ultimately leads to invasion, metastasis, and therapeutic resistance. Recent genome-wide sequencing data showed that APOBEC3B (A3B) contributes to mutational load in breast cancer. A3B, a DNA cytosine deaminase, is overexpressed in more than 50% of breast tumors and more than 75% of breast cancer cell lines. Its overexpression and aberrant activation lead to unexpected clusters of mutations in the majority of breast cancers. This phenomenon of clustered mutations, termed kataegis (shower in Greek) forms a unique mutation signature in breast cancer. On the basis of the finding that A3B is a key molecular determinant of the mutator phenotype in breast cancer, the goal of our research is to utilize informatics tools to systematically characterize genetic alterations of APOBEC3 family proteins in breast cancer genomic data and define the molecular impact of altered APOBEC3 family proteins on mutability and anti-tumor immunity. Our data showed that the mutation rate and copy number amplification/deletion of APOBEC3 genes are low. The levels of APOBEC3A (A3A) and A3B are highly correlated and are highest in Basal subtype and lowest in Luminal A tumors, in concordance with the proliferation of subtypes. Additionally, A3A and A3B are significantly correlated with total mutational load as well as with TP53 mutation, and with somatic copy number alterations (SCNA), especially focal SCNA. Among APOBEC3 genes, A3B is significantly associated DNA replication, DNA damage repair, cell cycle and proteasome signatures, and shows predictive and prognostic capacity in ER-positive patients. Interestingly, A3G expression is strongly associated with immune response signature genes in all breast tumors. Consequently, A3G is highly associated with tumor-infiltrating lymphocytes in breast and several other disease types. In summary, our data demonstrate distinct expression pattern of APOBEC3 genes in different breast cancer subpopulations. Overexpression of different APOBEC3 family members leads to distinct molecular consequences. These data provide new molecular insights into pathophysiological functions of APOBEC3 genes in breast cancer and provide therapeutic opportunities for the breast cancer patients whose tumors have altered APOBEC3 expression levels and potentially are driven by APOBEC3 genes. Importantly, APOBEC3G is associated with evidence of immune activation that may signal responsiveness to immune checkpoint inhibitors. Citation Format: Zhao W, Peng Y, Mills GB, Peng G. APOBEC3 contributes to mutational load in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD8-11.
F-18 FDG PET Images of Uterine Cervical Cancer Producing Granulocyte Colony Stimulating Factor
Authors: Masamichi Koyama, Kazumasa Hayasaka, Nobuhiro Takeshima, Hiroko Machida, Ken Takizawa
Journal: Clinical Nuclear Medicine (2010)

A 31-year-old woman developed intramenstrual spotting. A gynecologic examination revealed a cervical tumor with parametric invasion. Uptake on FDG PET images was intense at the uterine cervical tumor and accumulation was diffusely increased throughout the bone marrow. Severe leukocytosis was evident without a history of G-CSF administration or evidence of infection. Biopsy specimens of the uterine cervix revealed an invasive, nonkeratinizing-type squamous cell carcinoma. Uterine cervical cancers that produce hematopoietic growth factors are rare. The FDG PET findings of this patient helped to diagnose a tumor that produced G-CSF.
If you do well in the first two preclinical years but then go on to get a third class intercalated BSc, is your medical career over before it has even started?
Authors: Brian Angus
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Interaction of systolic blood pressure and resting heart rate with clinical outcomes in takotsubo syndrome: insights from the International Takotsubo Registry
Authors: Michael Böhm, Victoria L. Cammann, Jelena R. Ghadri, Christian Ukena, Sebastiano Gili, Davide Di Vece, Ken Kato, Katharina J. Ding, Konrad A. Szawan, Jozef Micek, Stjepan Jurisic, Fabrizio D'Ascenzo, Antonio H. Frangieh, Delia Rechsteiner, Burkhardt Seifert, Frank Ruschitzka, Thomas Lüscher, Christian Templin
Journal: European Journal of Heart Failure (2018)