tbuckley/cabot-search huggingface dataset:
Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.
Authors: Kyoko Kato, Yukiya Narita, Seiichiro Mitani, Kazunori Honda, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Takashi Ura, Masashi Ando, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2018)

152 Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.
Diploma/MA in Psychoanalytic Studies
Authors: Pat Tate
Journal: BMJ (2005)

Any graduate, not necessarily medical, “interested in bridging the gap between the clinical domain of contemporary psychoanalytic practices and the wider intellectual culture.” In fact, there were only a couple of doctors on the course.⇓



I did the taught, seminar part of the course in 1996-8, but I did not submit the dissertation for the degree until 2001 (the maximum delay allowed). The course is on Tuesday afternoons/evenings in term time for two years. In the first year, I was on sabbatical from full time general practice, but it …
QUANTIFICATION OF REVERSE TAKOTSUBO PATTERN IN PATIENTS WITH SUBARACHNOID HEMORRHAGE BY LONGITUDINAL STRAIN
Authors: Nobuyuki Kagiyama, Yuko Soyama, Elizabeth A. Crago, Masataka Sugahara, Nina E. Hasselberg, Theodore Lagattuta, Khalil Moh'd Yousef, Marilyn Hravnak, John Gorcsan
Journal: Journal of the American College of Cardiology (2018)
Immune Recovery Refines the Prognostic Impact of Minimal Residual Disease on Overall and Progression Free Survivals after Frontline Fludarabine, Cyclophosphamide and Rituximab (FCR) in CLL Patients
Authors: Martin Gauthier, Florence Durrieu, Michael Peres, Elodie Martin, Thomas Filleron, Christian Recher, Anne Quillet Mary, Loic Ysebaert
Journal: Blood (2017)
PERCUTANEOUS CORONARY INTERVENTION RATES IN NSTEMI CASES AND IN-HOSPITAL OUTCOMES IN THE UNITED STATES DURING YEARS 2002-2014
Authors: Armaghan Y. Soomro, Saqib Abbasi, Tahir Khan, Muhammad Rehan Raza, Victoria Teslova, Ruben Kandov, Gregory Maniatis, James Lafferty, Cindy Grines
Journal: Journal of the American College of Cardiology (2018)
SEX-DIFFERENCES IN THE SAFETY AND EFFICACY OF THE COMBO BIO-ENGINEERED STENT: FROM THE MASCOT POST-MARKETING REGISTRY
Authors: Jaya Chandrasekhar, Antonio Colombo, Melissa Aquino, Birgit Vogel, Tiong Kiam Ong, Michael Kang Yin Lee, Andres Iniguez, Lauren Joyce, Kamilia Moalem, Clayton Snyder, Samantha Sartori, Usman Baber, Debbie Morrell, Francesca Elmore, Stephen Rowland, Roxana Mehran
Journal: Journal of the American College of Cardiology (2018)
IMPACT OF METABOLIC SYNDROME AND/OR DIABETES ON LEFT VENTRICULAR MASS IN PATIENTS WITH SEVERE AORTIC STENOSIS BEFORE AND AFTER AORTIC VALVE REPLACEMENT
Authors: Ezequiel Guzzetti, Mohamed-Salah Annabi, Geraldine Ong, Anne-Sophie Zenses, Lionel Tastet, Erwan Salaun, Mylène Shen, Marie-Eve Piche, Paul Poirier, Philippe Pibarot, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2018)
Military faces shortage of doctors, review warns
Authors: Abi Rimmer
Journal: BMJ (2014)

The armed forces will have too few doctors to meet their future needs unless their recruitment of medical staff improves, the organisation that advises ministers on military pay has warned.1

The Armed Forces’ Pay Review Body (AFPRB) has issued a report on service medical and dental officers’ pay. The report said that, although the number of medical officers seemed to have increased, …
Dealing with bullying and harassment
Authors: Rekha Shroff
Journal: BMJ (2004)

Discrimination, bullying, and harassment can affect any doctor, but research shows that doctors from ethnic minority groups are most affected. For example, only 29% of doctors registered with the General Medical Council are overseas graduates, but 58% doctors who appear in front of the GMC conduct committee are from overseas.1 Also, only 18% of consultants are from ethnic minorities …
The REQUITE-AB study: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in breast cancer patients
Authors: T Rattay, K Johnson, D Azria, J Chang-Claude, S Davidson, A Dunning, D de Ruyscher, S Guiterrez-Enriquez, P Lambin, T Rancati, B Rosenstein, P Seibold, RP Symonds, H Thierens, R Valdagni, A Vega, A Webb, F Wenz, C West, C Talbot
Journal: Cancer Research (2017)

Clinically significant side-effects from radiotherapy affect around a quarter of breast cancer patients and may impact considerably on outcomes from treatment.  An increasing number of replicated genetic associations for radiotherapy toxicity are being reported[1],[2].  The EU-funded REQUITE consortium aims to validate genetic markers and clinical factors implicated in radiotoxicity.  The purpose of the REQUITE-AB project is to develop an integrated set of predictors for acute radiotherapy side-effects in breast cancer patients to be used as a clinical decision-making tool.As part of the REQUITE prospective cohort study, 2,000 patients eligible for adjuvant breast radiotherapy will be recruited in nine centres across Europe and North America between April 2014 and August 2016, with centralised data management, biobanking and two years’ follow-up using a standardised data collection protocol.  Patient characteristics and treatment details being captured also include dose-volume histograms and DICOM files.  Genotyping will take place in fall 2016.  Primary endpoints are acute skin toxicity (CTC-AE v4.0) and quality-of-life (QoL) on completion of radiotherapy and at 3 months from start of radiotherapy.  Secondary endpoints are late side-effects including change in breast appearance.1,766 breast cancer patients have been recruited to date with standardized documentation of toxicity and QoL.  Among patients who completed radiotherapy so far, 21.6% of patients developed grade 2 skin toxicity (brisk erythema) and 1.3% grade 3 (moist desquamation).  The ability of patient, treatment and genetic variables to predict clinical outcomes and QoL will be examined. The REQUITE study includes the largest radiogenomics cohort of breast cancer patients to date recruited under a single standardised protocol.  Findings of the REQUITE-AB project are likely to inform the development of interventional biomarker trials and personalise breast cancer care in the future. [1] Talbot et al, Br J Cancer, 2012; 107: 748-53.[2] Seibold et al, Int J Radiat Oncol Biol Phys, 2015; 92: 1084-92
Developing standards and indicators for quality improvement for cancer patients in Spain.
Authors: Eduardo Diaz-Rubio
Journal: Journal of Clinical Oncology (2015)

e17718 Background: Health and medical organizations should define quality standards to improve structures, processes and performance in oncology practices, helping to create a culture of self-evaluation and offering cancer patients a high quality care. ECO Foundation is an alliance of Spanish oncologists from leading cancer centers with the mission of advancing towards excellence in patient care, research and continuous medical education Methods: The main objectives of this project are to promote a culture of continuous improvement among individuals and practices, to reduce unwarranted clinical variability and to fulfill patients and professionals needs. The project to assess the quality care of oncology practices in Spain was developed in four stages: 1) Evidence and regulated search from literature to identify quality care criteria; 2) Expert review and validation from top leading oncologists; 3) Professional consensus and endorsement through Delphi methodology; 4) Developing quality indicators and standards for the selected criteria. The areas selected were: Organization, Colorectal, Breast and Lung Cancer and Palliative Care. Results: In a first approach, a total of 98 recommendations were identified. After the consensus reached through the Delphi method, 56 quality items were selected nationwide (Table). Implementation of multidisciplinary committees, patient safety, diagnostic and therapeutic intervals and delays, anatomic pathology and biomarkers report, patient information and supportive care, are some of the principal topics included Conclusions: Indicators are a reference model based on standards in order to measure quality care. The goal is to achieve a reference tool among Spanish oncology practices for quality self-assessment and in a second phase, to offer a quality certification process. To be effective and efficient, a public health service needs to obtain optimal health outcomes and ensure the maximum objective quality for the patient. Quality indicators classification by area and type. Type of criteria ORGANIZATION COLORECTAL BREAST LUNG PALLIATIVE CARE TOTAL Structure 1 0 0 0 2 3 Process 7 9 7 5 6 34 Performance 4 1 4 7 3 19 TOTAL 12 10 11 12 11 56
Pre-hospital emergency care
Authors: Sabrina Butcher
Journal: BMJ (2009)

The pre-hospital emergency care course is certified by the Royal College of Surgeons of Edinburgh and run by the British Association for Immediate Care. It can be used towards the diploma in immediate care (DIMCRCSEd).

I did the course through the British Association for Immediate Care Scotland at Craigellachie, a remote location in north east Scotland, although courses take place in a number of rural locations throughout Scotland. The organisers allowed a maximum of 16 people on the course. It runs over two and a half days and consists of a series of lectures and practical teaching sessions in small groups.

Various aspects of trauma are explored, including extrication from vehicles, and cardiac scenarios similar to those on the advanced life …
<i>MPO</i> Promoter Polymorphism rs2333227 Enhances Malignant Phenotypes of Colorectal Cancer by Altering the Binding Affinity of AP-2α
Authors: Qingtao Meng, Shenshen Wu, Yajie Wang, Jin Xu, Hao Sun, Runze Lu, Na Gao, Hongbao Yang, Xiaobo Li, Boping Tang, Michael Aschner, Rui Chen
Journal: Cancer Research (2018)

Myeloperoxidase (MPO) promoter SNPs rs2243828 (-764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2α to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A-MMP9 axis-mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of colorectal cancer.Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer. Cancer Res; 78(10); 2760-9. ©2018 AACR.
One in 20 trainees concerned about patient safety
Authors: Helen Jaques
Journal: BMJ (2012)

One in 20 trainees in the UK has concerns about patient safety at the organisation where they train, the General Medical Council’s annual survey of doctors in postgraduate training has found.

Early analysis of the responses from more than 51 000 trainees indicates that the major issues are in the acute specialties, reflecting the pace and intensity of those specialties, the GMC has said.

The fact that 5% of trainees did raise a concern of one kind or another suggests that there may be some “significant issues” around patient safety in the UK, the regulator has said, although it cautions that it is too early to draw any firm conclusions …
Urticaria and Episcleritis in a Woman With Chronic Cough
Authors: Christina Dai, David Weinstein
Journal: JAMA Dermatology (2018)

A woman in her 30s presented with a 10-month history of painful pruritic eruption and painful red eyes; the eruption was exacerbated by stress but unrelated to time of day, ambient temperature, or sunlight exposure. She also reported recent worsening of a chronic cough. What is your diagnosis?
Carbohydrate‐based vaccines for oncotherapy
Authors: Meng‐Man Wei, Yong‐Shi Wang, Xin‐Shan Ye
Journal: Medicinal Research Reviews (2018)

Abstract Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor‐associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines.
MA in bioethics
Authors: Helen Barratt
Journal: BMJ (2006)

This two year part time course is designed for anyone concerned about ethical issues in medicine and biotechnology, and particularly those wishing to examine the issues more deeply in the context of theology. Course participants included doctors and other medical students, as well as medical lawyers and interested laypeople. It is taught at St Mary's College, Twickenham, and leads to an MA conferred by the University of Surrey.

I completed the course while I was still at medical school, but doctors at all …
S1P–S1PR2 Axis Mediates Homing of Muse Cells Into Damaged Heart for Long-Lasting Tissue Repair and Functional Recovery After Acute Myocardial Infarction
Authors: Yoshihisa Yamada, Shohei Wakao, Yoshihiro Kushida, Shingo Minatoguchi, Atsushi Mikami, Kenshi Higashi, Shinya Baba, Taeko Shigemoto, Yasumasa Kuroda, Hiromitsu Kanamori, Mohamad Amin, Masanori Kawasaki, Kazuhiko Nishigaki, Masato Taoka, Toshiaki Isobe, Chisako Muramatsu, Mari Dezawa, Shinya Minatoguchi
Journal: Circulation Research (2018)

Rationale: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3 + cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. Objective: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair. Methods and Results: In vivo dynamics of Nano-lantern–labeled Muse cells showed preferential homing of the cells to the postinfarct heart at 3 days and 2 weeks, with ≈14.5% of injected GFP (green fluorescent protein)-Muse cells estimated to be engrafted into the heart at 3 days. The migration and homing of the Muse cells was confirmed pharmacologically (S1PR2 [sphingosine monophosphate receptor 2]–specific antagonist JTE-013 coinjection) and genetically (S1PR2-siRNA [small interfering ribonucleic acid]–introduced Muse cells) to be mediated through the S1P (sphingosine monophosphate)–S1PR2 axis. They spontaneously differentiated into cells positive for cardiac markers, such as cardiac troponin-I, sarcomeric α-actinin, and connexin-43, and vascular markers. GCaMP3 (GFP-based Ca calmodulin probe)-labeled Muse cells that engrafted into the ischemic region exhibited increased GCaMP3 fluorescence during systole and decreased fluorescence during diastole. Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells. These effects were partially attenuated by the administration of GATA4 -gene–silenced Muse cells. Muse cell allografts and xenografts efficiently engrafted and recovered functions, and allografts remained in the tissue and sustained functional recovery for up to 6 months without immunosuppression. Conclusions: Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.
Single-cell protein analysis in support of biomarker evaluation for breast cancer immunotherapeutics.
Authors: Vicki Plaks
Journal: Journal of Clinical Oncology (2018)

10 Background: Triple-negative breast cancer (TNBC) is being tested for PD-1/PD-L1 checkpoint inhibitors combination therapy. The relationship between tumor expression of PD-L1 and patient outcomes has been established using immunohistochemistry (IHC) biomarker assays across various malignancies. PD-L1 is expressed in tumor and immune cells within the tumors in TNBC, but only immune-cell PD-L1 is associated with response to anti-PD-L1 (atezolizumab) so differentiating tumor vs. immune PD-L1 expression is essential. The currently available IHC biomarker assays that relay on tissue biopsies struggle to provide clinically meaningful identification of responders vs. non-responders. Poor sensitivity and specificity is partially attributed to tumor heterogeneity that is not well-represented in these biopsies. In addition, PD-L1 expression may vary over time due to disease progression or treatment. Since tissue biopsy collection is often an invasive procedure, it is restricted. Needle biopsies can mitigate some of these issues as a minimally invasive method to probe multiple regions within several cancer lesions across several time points. MILO, a new single cell Western Blot (WB) technology allows quantitative measurements of multiple protein biomarkers within one cell in small samples. Methods: To evaluate the capability of MILO to differentiate between PD-L1 in immune and tumor cell populations, we interrogated BC cell lines as well as peripheral blood mononuclear cells (PBMCs) mixed in known ratios. We used MDA-MB-231 that shows high PD-L1 and low HER2 expression and BT-474, which shows the inverse expression profile for these biomarkers along with PBMCs as PD-L1+ immune cells. Primary breast tumor tissues are currently interrogated to establish utility in needle biopsies. Results: MILO demonstrated heterogeneity at the single-cell level of HER2 and PD-L1 expression in BC tumor cells and enabled differentiation between PD-L1 expression in immune vs. tumor cells using cell-specific markers and low cell numbers. Conclusions: MILO can improve patient selection and prediction of response to immune checkpoint inhibition by promoting the utility of needle biopsies to complement IHC of core biopsies.
USE OF LACE INDEX TO PREDICT THE RISK OF READMISSION IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE IN A PREDOMINANT HISPANIC POPULATION
Authors: Eder Hans Cativo Calderon, Tuoyo Mene-Afejuku, Diana P. Cativo, Persio Lopez, Hans Reyes Garay, Marco Ruiz, Ferdinand Visco
Journal: Journal of the American College of Cardiology (2018)
Surgery for brain tumours without deploying hand-held or self-retaining retraction systems
Authors: Kishor Choudhari, Shashank Joshi
Journal: Neuro-Oncology (2018)

To assess utility of not deploying retractor systems during radical surgery for parenchymal and intraventricular brain tumours and to analyse its effect on post-operative complications and extent of resection. Gross total resection (GTR) was attempted in all patients. Neuronavigation and intra-operative imaging was utilised as necessary. Endoscopic surgeries, stereotactic burr-hole biopsies or aspirations were excluded. Patients did not receive anti-oedema drugs in peri-operative period. Anticonvulsants were administered only if patient had pre-operative seizures or an inflammatory pathology was suspected. Patients had post-operative evaluation immediately after surgery and 12 hourly intervals for three days. All patients had imaging within 48 hours of surgery to assess tumour-bed haematomas, cerebral swelling and extent of resection. Consecutive 338 patients of intrinsic and intraventricular tumours operated from 2010–15 period at a tertiary referral Institution by two consultants with special interests in neuro-oncology. Male to female ratio 45:55. Age range 5 months to 78 years. Apart from 8 intraventricular tumours, 11 brain abscesses and 39 metastases, the remainder of cases were primary brain tumours. Gross total resection was accomplished at surgery in over 90 percent of cases. There was four post-operative deaths; seven patients had new, non-resolving clinical deficits and a further four patients had new onset seizures. Only one patient experienced tumour-bed haematoma requiring surgical evacuation. Brain swelling on comparison imaging was considerably reduced in all but three patients. Not employing self-retaining retraction systems during intrinsic brain tumour surgery appears to be associated with reduced post-operative complication rates without compromising the extent of resection.