tbuckley/cabot-search huggingface dataset:
Radiation associated angiosarcoma of the the breast treated with trimodality of surgery, radiation, and paclitaxel-based chemotherapy.
Authors: Halle Elizabeth Foss, Ivy Ann Petersen, Amy C. Degnim, Robert Mutter, Steven Ian Robinson, Scott H. Okuno
Journal: Journal of Clinical Oncology (2015)

e21532 Background: Radiation associated angiosarcoma (RAAS) of the breast is rare and occurs in only 0.1-0.6% of those treated with breast conservation therapy (BCT). With resection alone there is a high risk of recurrence. The addition of chemotherapy (CT) and radiation therapy (RT) for RAAS has shown promising results and we review our experience with tri-modality therapy (pre-operative CT and RT followed by surgery) for RAAS. Methods: After IRB approval, we identified 35 patients treated with RAAS between January 2000 and March 2014. Data was compiled for demographics, type of surgery, type of chemotherapy, and dose of radiation therapy. The relationship between treatment regimen and time/rate of recurrence was explored. Results: Of patients with RAAS who underwent surgery alone as definitive treatment (n = 20), 85% recurred locally after a median follow up of 15 months. Those who received tri-modality therapy (n = 5) showed a local recurrence rate of 0% after a median follow up of 11 months (6-48). At recurrence of RAAS following surgery alone, patients treated with surgery alone (n = 6) for a second time had a local recurrence rate of 83% after a median follow up of 12 months, whereas patients treated with tri-modality therapy (n = 5) showed a local recurrence rate of 0% after a median follow up of 20 months (13-61). All patients treated with tri-modality therapy received paclitaxel-based chemotherapy and the median dose of radiation was 50 gray units (Gy). Conclusions: This retrospective study confirms that there is a high recurrence rate of RAAS after surgery alone. Using surgery in combination with pre-operative paclitaxel-based CT and RT substantially decreases the RAAS local recurrence rate. Further study with longer follow up and a larger sample size is planned.
Minerva: October 1999
Authors: G R Ellis, M R Stephens
Journal: BMJ (1999)

Adding iron to formula milk can prevent iron deficiency in babies but doesn't boost their growth or development ( Archives of Disease in Childhood 1999;81:247-52). Nine month old babies given formula milk fortified with iron did no better over nine months than children fed pasteurised cows' milk in a randomised trial, although they had higher plasma ferritin concentrations. Anaemic toddlers may still benefit from iron supplements in their milk, however, so bigger trials in more mixed populations should be done to find out, say the authors.

Supplements, or fortifiers, can also be added to human milk to improve its nutritional value to low birthweight infants. Unfortunately, commonly used fortifiers increase the milk's osmolality, a European team of researchers has found ( Archives of Disease in Childhood Fetal and Neonatal Edition 1999;81:F141-3). Clinically important increases in osmolality occur within minutes and continue for at least 24 hours, probably because amylases in breast milk break down polysaccharides in the supplement.

Elderly patients wanting to know if they are fit to drive may not get the right answer from a doctor ( Postgraduate Medical Journal 1999;75:537-9). In a survey of 50 doctors attached to one geriatric unit …
Five-year prognosis of breast cancer patients in Conakry Hospital University (West Africa).
Authors: Bangaly Traore, Abdoulaye Toure, Telly Sy, Mamadou Moustapha Dieng, Mamoudou Conde, Ahmadou Dem, Namory Keita, Bakary Sidiki Sylla
Journal: Journal of Clinical Oncology (2015)

e12065 Background: Surgical operation for breast cancer remains one of the major therapeutic approaches for management of breast cancer. This retrospective study aims to review different factors associated with relapse and mortality in breast cancer patients in restricted-resource settings over a five years period. Methods: Study design: Retrospective cohort study including133 women underwent breast cancer surgery was performed at Surgical Oncology Unit of Conakry University Hospital. Data collection: Sociodemographical characteristics, clinical information, treatment and data on relapse and survival were abstracted from medical files. The prognostic within 5 years of surgery was recorded. Data Analysis: Predictor factors of relapse were analyzed by using univariate and multivariate logistic regression and factors associated with mortality were analyzed by Kaplan Meier survival and Cox models. Results: The mean age of patients was 48.0 ± 12.4 years and mainly the housewives (51.8%). Main types of cancer were ductal invasive carcinoma (64.7%). Breast cancer surgery was conservative in 13 cases (9.8%) and radical in 120 cases (90.2%). The median time from diagnostic to cancer surgery was 5.0 (IQR: 3.0 – 7.0) months. Five-year relapse was 33.8 ± 8.0 % and the median time from surgery to relapse was 7.0 (IQR: 3.0 – 15.0) months. Predictor factors of relapse were age (OR = 0.94; P = 0.005), and stage III and IV of cancer [OR = 6.30; P = 0.005)]. The overall 5 -year mortality was 42.1% (95%CI: 33.6 – 50.6%) and the risk factors independently associated with death were body mass index [HR = 1.10, P = 0.01], origin of patients [HR = 2.14, P = 0.02], radiotherapy [HR = 0.46, P = 0.01] and cancer relapse [HR = 7.0, P = 0.001]. Conclusions: The proportions of relapse and death were higher in breast cancer patients. Age and stage of cancer at time of surgery were the predictors of relapse and body mass index, origin of patients, radiotherapy and cancer relapse were associated with death.
TCTAP C-107 A Case of Diamond Against Platinum (Rotablation of Drug-eluting Stent)
Authors: Chin Keong Gary Lee, Kamaraj Selvaraj, Asri Ranga Abdullah Ramaiah, Abdul Muizz Bin Abd Malek, Yoke Loong Foo, Ahmad Fazli Abdul Aziz, Abd Kahar Bin Abd Ghapar
Journal: Journal of the American College of Cardiology (2019)
Noninvasive 3D analysis of sputum cells for lung cancer early detection with high specificity: A blinded study.
Authors: Michael Meyer, Chris Presley, Rahul Katdare, David W. Wilbur, Alan C. Nelson, Tim Bell
Journal: Journal of Clinical Oncology (2015)

e18527 Background: The LuCED test for lung cancer early detection analyzes non-invasive sputum using the Cell-CT system that images cells in true 3D to measure the biosignatures of cancer. Morphometric classifiers process the 3D cell biosignatures to distinguish normal cells from abnormal cell candidates. A pathologist using the CellGazer workstation views images of these abnormal cell candidates to determine the diagnosis. Prior work demonstrated LuCED case sensitivity to early stage lung cancer of 95% with 99.8% cell specificity. This study offers a blinded assessment of LuCED’s clinical performance. Methods: 19 cases were studied: 7 normal cases and 12 biopsy-confirmed non-small cell and small cell lung cancer cases. 9 cancer cases were stage I or II. The remaining 3 late stage cancer cases had tumor sizes that were less than three 3cm. When an abnormal case is detected, typically more than one abnormal cell is involved so only cases with 2 or more abnormal cells were included as LuCED positives. Cases were randomized and all cell review was done in a blinded fashion so that the pathologist did not have access to the case diagnosis. Results: Normal cases: Cell –CT analysis identified 0.3% of 77,148 cells (or 99.7% cell specificity) as abnormal cell candidates. The 95% confidence interval for cell specificity is 99.66 to 99.74%. Pathologist review using CellGazer of the abnormal cell candidates produced zero false positive cells. The case specificity is 100%. Abnormal cells were detected by LuCED and confirmed by the pathologist in 11 of the 12 biopsy confirmed cancer cases. The case sensitivity is 91.7%. The missed case was a stage IB adenocarcinoma with a 4.5cm tumor occurring in the left upper lobe. Conclusions: This initial, blinded study of LuCED confirms earlier projections that LuCED sensitivity to early lung cancer exceeds 90% while maintaining exceedingly high specificity. This performance suggests an important role for the non-invasive LuCED test as an adjunct to Low dose CT screening, to dramatically reduce the inherent false positives and confirm positive diagnoses.
Phase II study of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study
Authors: M. Shimokawa, K. Nosaki, T. Seto, K. Ohashi, M. Morise, Y. Fujiwara, J. Sakakibara, H. Murakami, S. Yano, M. Satouchi, S. Matsumoto, K. Goto, K. Yoh
Journal: Annals of Oncology (2019)

Background: The majority of non-small cell lung cancer (NSCLC) patients are diagnosed as metastatic disease for which no curative treatment is available. Phase III randomized trials of tyrosine kinase inhibitor (TKI) therapy for EGFR-mutant and anaplastic lymphoma receptor tyrosine kinase (ALK)-rearranged lung cancers have documented improvements in response and progression-free survival (PFS), and TKIs are approved for the treatment of patients with oncogene-driver mutations. c-Met is the tyrosine kinase receptor for hepatocyte growth factor, and MET gene alterations including MET exon14 skipping mutation-positive or MET high gene copy number are known to be an oncogene via activation of c-MET signaling pathway. Crizotinib is a selective ATP-competitive small-molecule inhibitor of c-Met, ALK and ROS1 tyrosine kinases. Durable responses to crizotinib were reported in patients with advanced NSCLC harboring MET exon 14 skipping mutation or high MET gene copy number. Therefore, we considered to assess the efficacy and safety of crizotinib in patients with advanced NSCLC harboring a MET gene alteration. Trial design: Co-MET is an open-label, multi-center, 2 cohort single-arm phase II trial of oral crizotinib in patients with advanced NSCLC harboring MET exon 14 skipping mutations without prior MET TKI treatment (cohort 1) or high MET gene copy number of 7 or more (cohort 2). The status of MET gene alterations will be determined using a validated RT-PCR assay and/or NGS. Crizotinib, 250 mg BID, will be administered orally continuously until disease progression or unacceptable toxicities. All tumor scans will be reviewed by an independent radiology committee according to RECIST version 1.1. The primary endpoint is objective response rate (ORR). Assuming a null hypothesis of a 20% ORR and an alternative hypothesis of a 50% ORR for cohort 1, and a one-sided type I error of 0.05 (one-side) and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. The sample size for cohort 2 is empirically set at 10 patients. Clinical trial information: UMIN000031623. Clinical trial identification: UMIN000031623. Legal entity responsible for the study: The authors. Funding: Japan Agency for Medical Research and Development. Disclosure: K. Nosaki, S. Matsumoto: Honoraria: Pfizer Japan Inc. T. Seto: Honoraria, research grants: Pfizer Japan Inc. H. Murakami: Personal fees: Pfizer Japan Inc. K. Goto: Honoraria, research funding: Pfizer Japan Inc. K. Yoh: Research funding: Pfizer Japan Inc. All other authors have declared no conflicts of interest.
Freakoncology: Is there an optimistic denial in the ipilimumab publications?
Authors: Ernesto Gil Deza, Mario Javier Nacul, Carlos Fernando Garcia Gerardi, Eduardo L. Morgenfeld, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2015)

e20122 Background: optimism in oncologists is essential but excess optimism leads us to deny reality. To study this phenomenon in scientific publications we searched for "Ipilimumab" in PubMed. Methods: The terms "Ipilimumab in human" were searched in PubMed until November 4, 2014. Two independent researchers categorized the title and abstracts as: Positive (Pos) (focus on benefit); Negative (Neg) (focus on toxicity) or Neutral (Neu) (mentioning both benefits and toxicity). All categories were then compared with respect to the type of publication: a) oncological vs. non-oncological, b) international vs. national, c) free full text yes or no, d) date of publication prior to or after the pivotal phase III trial (August 2010), e) value of impact factor of publications according the Journal Citation Reports. Results: 533 publications fulfilled the inclusion criteria. Rating: Pos 286 (54%), Neg 108 (20%), Neu139 (24%) Only seven publications (1%) associated with three phase III trials were identified. The table below shows the studied variables. Conclusions: 1) Oncological publications are frequently positive, reflecting the "optimistic" view of authors, editors and publishers. 2) Many severe toxicities reports are only published in non-oncological journals. We ignore the reasons for such findings if we discard any conflicts of interest 3) A single phase III study published in a high impact journal greatly influenced the tone of subsequent publications and promoted the utilization of this high cost medication. Publications Total Pos Neg Neu Chi squared Onc vs Non Onc 274 vs 259 175 vs 111 30 vs 78 69 vs 70 p = 0.0001 International vs National 174 vs 379 100 vs 186 37 vs 71 37 vs 102 P = 0.21 Free full text yes vs no 194 vs 339 113 vs 173 31 vs 77 50 vs 89 P = 0.13 Pre vs Post August/2010 70 vs 463 27 vs 259 15 vs 93 28 vs 111 P = 0.009 Impact Factor: media (range) 7.3 (0-88.55) 7.4 (0-88.55) 8.37 (0-54.42) 6.4 (0-54.42) Kruskal-Wallis p = 0.497
A borderline HbA <sub>1c</sub> result
Authors: Eleanor Barry, Samuel Finnikin
Journal: BMJ (2019)

### What you need to know

A 55 year old white man attends his annual hypertension review. His glycated haemoglobin (HbA1c) is 44 mmol/mol. He has a body mass index (BMI) of 31 kg/m2 and his cholesterol is raised. 

Pre-diabetes is an umbrella term used to describe blood glucose levels that are above normal but below the diagnostic threshold for diabetes.1 In practice this is most commonly where a patient’s glycated haemoglobin (HbA1c) value is between 42 and 48 mmol/mol, but it also encompasses impaired fasting glucose and impaired glucose tolerance. The term “pre-diabetes” is the subject of much debate, with some favouring “non-diabetic hyperglycaemia.” This reveals an underlying tension between a desire to prevent a medical diagnosis (diabetes) and the potential harms of over-medicalising people based on laboratory proxies for health.2 In this article we outline our approach to a consultation with someone with a borderline HbA1c approach.

The initial focus of the consultation is to establish the patient’s individual risk of developing diabetes. This will enable an informed discussion of that risk and the options available.

A blood test in isolation will not identify those at greatest risk of developing diabetes. Those with the greatest progression rates are people with dysglycaemia and multiple risk factors for diabetes. These are listed in box 1. To identify those most at risk …
THU-335-FXR rs35724 C &gt;G variant modulates cholesterol levels, carotid atherosclerosis and liver damage in non-alcoholic fatty liver
Authors: Stefania Grimaudo, Paola Dongiovanni, Rosaria Maria Pipitone, Guido Alessandro Baselli, Calogero Camma, Daniela Cabibi, Vito Di Marco, Miriam Longo, Grazia Pennisi, Silvia Fargion, Antonio Craxi, Luca Valenti, Salvatore Petta
Journal: Journal of Hepatology (2019)
AB0136 Aortic involvement in ankylosing spondylitis
Authors: J Hrba
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In ankylosing spondylitis (AS) the occurrence of involvement of ascending aorta and aortic (and sometimes mitral) valve is known. The microscopic changes include inflammatory destruction of aortic and valvular tissue and replacement by granulation and fibrous tissue. Aortic regurgitation results from thickening and displacement of valve cusps and dilatation of aortic root. It may be clinically silent or may cause severe problems to the patient. Immunosuppressive therapy may prevent or delay the need for aortic valve replacement but many times valve replacement is the only life-saving therapy. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> Recently we had an opportunity to treat 3 patients with AS and aortic incompetence. All three were suffering from AS with peripheral arthritis. In one patient aortic failure was complicated with bacterial endocarditis although previous symptoms of aortic failure were only subclinical. In the second patient aortic insufficiency proceeded very rapidly to severe and life-threatening cardiac failure. In both of them aortic valve replacement was successful. Interestingly, in the second patient massive immunosuppressive therapy prior to cardiosurgery led to a significant improvement of cardiac failure. The third patient has not been suffering from any cardiac troubles but the clinical and x-ray examination (aortography) revealed a significant aortic regurgitation. <h3>Conclusion</h3> It is a matter of interest that the second patient had some features of Marfan's syndrome and the third had some features of Ehlers-Danlos syndrome. It raised the question which of these two components ? inflammation or primary defect of collagen or both of them participates in the aortic involvement.
LBP-01-In NAFLD, alcohol drinking habits and genetics predict progression to advanced liver disease: follow-up of population surveys
Authors: Fredrik Åberg, Pauli Puukka, Perttu Sahlman, Markku Nissinen, Veikko Salomaa, Satu Männistö, Annamari Lundqvist, Liisa Valsta, Markus Perola, Antti Jula, Martti Färkkilä
Journal: Journal of Hepatology (2019)
THU-125-High real-world effectiveness of elbasvir/grazoprevir in PWID on opioid substitution therapy with HCV genotype 1 infection: Results from the German hepatitis C registry (DHC-R)
Authors: Stefan Christensen, Albrecht Stoehr, Markus Cornberg, Hartwig Klinker, Renate Heyne, Christine John, Karl-Georg Simon, Manfred Bilzer, Veronika Guenther, Vanessa Witte, Jens Reimer
Journal: Journal of Hepatology (2019)
Regulation of Stat3 by reactive oxygen species
Authors: Shing-Hu Cheung, Li Li, Stephanie Vougier, Peter E Shaw
Journal: Cancer Research (2008)

867  STAT3 has fundamental importance for vertebrate organisms and has been implicated in driving cell proliferation in several human tumor types. In addition, reactive oxygen species (ROS) are regarded as having oncogenic potential and elevated levels of ROS have been associated with tumor promotion.  We have observed in electrophoretic mobility shift assays (EMSAs) that STAT3 DNA binding activity is reduced in the presence of hydrogen peroxide whereas binding by STAT1 is not. We sought to identify the region of STAT3 that confers redox sensitivity. A comparison of STAT1/STAT3 chimeras indicated that the DNA binding domain and carboxyl-terminal region of STAT3 harbor elements that are redox sensitive. Since cysteine residues in polypeptides can be sensitive to oxidation, we substituted cysteine to serine in these regions. This gave rise to STAT3 mutants that were partially or completely insensitive to peroxide in EMSAs.  The effect of ROS on the transcriptional activity of STAT3 was examined in HepG2 cells with the c-fos SIE in a luciferase reporter assay. With wild-type STAT3 we observed a decrease in the IL-6 induction of the SIE reporter in the presence of peroxide whereas the transcriptional activity of the mutant STAT3s remained unchanged, suggesting that wild-type STAT3 is directly sensitive to redox control in cells. Tyrosine phosphorylation of STAT3 in IL-6 stimulated cells was not affected by ROS, indicating that the loss of STAT3 activity was not due indirectly to a decrease in phosphorylation.  We have previously used chromatin immunoprecipitation (ChIP) assays to show that STAT3 binding to the c-fos promoter in HepG2 cells is stimulated by IL-6. Here we also show that IL-6 induced binding of STAT3 to the c-fos promoter is decreased by peroxide, which is consistent with the loss of activity observed in reporter assay and EMSAs. We are now investigating to what extent such observations can be extended to other STAT3-responsive promoters.  We, and others, have previously observed that ROS scavengers and inhibitors of ROS generating systems can reduce STAT3 activity. Here we show that ROS can also reduce STAT3 activity directly and specifically. Thus STAT3 function appears to be restricted to a window of intracellular oxidative potential, which could play a role in linking cell metabolism with proliferation and survival.
FRI-298-Hypoxia-inducible factor 2 alpha drives lipid accumulation in human hepatocytes through the fatty acid translocase CD36
Authors: Carmelo García-Monzón, Esther Rey, Florinda Meléndez-Rodríguez, Patricia Marañón, Elvira Del Pozo-Maroto, Javier Rodríguez de Cía, Julián Aragonés, Águeda González
Journal: Journal of Hepatology (2019)
LBP-23-Prognostic Impact of Peritumoral Neutrophil Infiltration on Hepatocellular Carcinoma Recurrence Following Liver Transplantation
Authors: Marc Najjar, Karim Halazun, Ayush Srivastava, Michael Moore, Donian Chyong, Robyn Gartrell, Emanuelle Rizk, Evan Lieberman, Olivia Perez, Shelief Robbins-Juarez, Charles Drake, Ladan Fazlollahi, Helen Remotti, Jean Emond, Yvonne Saenger
Journal: Journal of Hepatology (2019)
Extent of desired disclosure of cancer bad news by patients, their relatives and the public.
Authors: Jamal M Zekri, Syed Mustafa Karim
Journal: Journal of Clinical Oncology (2015)

e20588 Background: Empowering cancer patients requires them to be continually updated in detail about their condition. This concept is often opposed by care givers in some eastern cultures. We aim to compare the extent of disclosure desired by actual and presumed cancer patients and relatives in our practice. Methods: Nine questions reflecting possible bad news communication to patients from diagnosis to end of life were designed to investigate the extent of desired disclosure, and were answered by 100 patients (cohort I) and 103 accompanying relatives (cohort II) in an out-patient oncology setting. Also 103 public members attending family medicine clinic (cohort III) each answered the questions from a presumed patients’ (IIIA) and relatives’ (IIIB) perspective. The primary endpoint was affirmative response to ≥ 6 questions (AR ≥ 6) indicating preference to be informed of majority (≥ 67%) of possible bad news. Results: AR ≥ 6 was reported in 85% of cohort I and 52% of cohort II (Chi2P < 0.001). On multi-variate linear regression analysis (MVA) (Table), AR ≥ 6 showed significant association with being a patient (in cohort I&II) and having non-metastatic disease (only cohort I). In the public cohort, AR ≥ 6 was reported in 91% and 63% in cohorts IIIA and IIIB respectively (P < 0.001). On MVA, AR ≥ 6 in cohort III was significantly associated with being a presumed patient and having atleast university education. Conclusions: Patients desire disclosure of majority of cancer related bad news. This is in contrast to relatives’ views and requests. The public would also desire similar disclosure if they were to be diagnosed with cancer. Interestingly, this notion changes if their relatives were to be diagnosed with cancer. Cohort I&II HR (95% CI), P value Cohort III HR (95% CI), P value Age 0.53 (0.26-1.08) P = 0.08 1.34 (0.55-3.24) P = 0.52 Gender 0.98 (0.44-2.22) P = 0.97 0.089 (0.39-2.01) P = 0.78 Less than university education 0.95 (0.48-1.90) P = 0.87 0.24 (0.11-0.56) P = 0.001 Employed vs not 1.40 (0.62-3.16) P = 0.42 0.83 (0.35-1.99) P = 0.68 Being a patient vs. relative 4.35 (2.15-8.79) P < 0.001 7.11 (3.05-16.59) P < 0.001 *Metastatic vs. non-metastatic cancer 0.18 (0.04-0.70) P-0.014 *Active vs. non active treatment 2.66 (0.69-10.25) P = 0.15 *Cohort I only