tbuckley/cabot-search huggingface dataset:
Cardiac Disease After Breast Cancer Treatment: Make Sure to Check Our Blind Spot!
Authors: Daniel J Lenihan
Journal: JNCI Journal of the National Cancer Institute (2018)

report on a population-based retrospective study of a long-term analysis of the cardiovascular (CV) outcomes of patients with early breast cancer (EBC) who have undergone treatment in Ontario, Canada (1).These data are very carefully reviewed and synthesized.The treated patients are compared to a control group of age-matched patients on a 1:3 ratio allowing a robust comparison for CV risk factors and outcomes in these patients with breast cancer to an appropriate control population.These authors report on some very interesting findings, especially when compared to previous work in similar breast cancer groups.In short, the authors report that even among patients treated with potentially cardiotoxic therapy, such as anthracyclines or trastuzumab, the rate of admission for heart failure (HF) is surprisingly low, even after 10 years, especially when one considers that the most common cardiac issue encountered in these patients being treated for cancer is actually coronary artery disease or the development of ischemic heart disease (IHD).This report also deals with other common CV events such as stroke and arrhythmia, which thankfully occur at a low rate over 10 years but still occur more frequently than control patients during that time.It is expected that patients with EBC, especially those treated with anthracyclines and/or trastuzumab, would have a higher incidence of HF hospitalization compared to age-matched patients.Fortunately, the overall risk of HF related to chemotherapy or targeted therapy is much lower than that seen with other large database studies reported previously and portends an overall excellent CV prognosis despite cancer treatment (2,3).Abdel-Qadir et al. should be congratulated on many fronts.The long period of follow-up of 10 years definitely allows a practitioner to understand the long view of cancer treatment as it relates to CV disease.There is extensive information about concomitant medications and CV risk factors, which allows one to see that this population does represent a "real-world"
Serum cell‐free DNA levels are a useful marker for extramammary Paget disease
Authors: T. Mijiddorj, I. Kajihara, Y. Tasaki, S. Otsuka‐Maeda, R. Sakamoto, S. Sawamura, S. Kanazawa‐Yamada, S. Egashira, K. Inoue, K. Makino, A. Miyashita, J. Aoi, T. Igata, T. Makino, S. Masuguchi, S. Fukushima, M. Jinnin, J. Morinaga, T. Ikeda, H. Ihn
Journal: British Journal of Dermatology (2019)

Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell‐free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell‐free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.
Abstract #2707: Design and synthesis of dual PI3K/mTor inhibitors
Authors: Alan Olivero, Timothy Heffron, Leanne Berry, Megan Berry, Georgette Castanedo, Christine Chang, Jennafer Dotson, Lori Friedman, Richard Goldsmith, John Lesnick, Cristina Lewis, Simon Mathieu, Jim Nonomiya, Jodie Pang, David Peterson, Wei Wei Prior, Laurent Salphati, Deepak Sampath, Daniel Sutherlin, Vickie Tsui, Mark Ultsch, Shumei Wang, Christian Wiesmann, Susan Wong, Bing-Yan Zhu, Irina Chuckowree, Adrian Folkes, Steve Shuttleworth
Journal: Cancer Research (2009)

Because the phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a crucial role in many aspects of cell growth and survival, inhibitors of the pathway offer great potential in the treatment of cancer. We have recently reported the discovery of potent and orally bioavailable pan inhibitors of PI3K, including the inhibitor GDC-0941. As part of our continued interest in the design of novel PI3K inhibitors, we embarked on a program to further probe key binding pockets in PI3K as well as increase structural diversity of our inhibitors. Through structure based design driven by crystallography in PI3Kgamma and systematic modification of our lead chemical series, new inhibitors that take advantage of alternative binding interactions in the PI3K ATP site have been identified. Because of the enhanced affinity of some new interactions, potent (IC50-p110a   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2707.
Innate Lymphoid Cells (ILCs) Generate Memory for Pathogen-Associated Molecular Patterns (PAMPs) of Allergens, Which Contributes to Asthma
Authors: Mukesh Verma, Lidia Michalec, Anand Sripada, Jerome McKay, Kapil Sirohi, Nathan T. Dyjack, Magdalena M. Gorska, Max Seibold, Richard J. Martin, Rafeul Alam
Journal: Journal of Allergy and Clinical Immunology (2019)
Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
Authors: Serena Sanna, Natalie R. van Zuydam, Anubha Mahajan, Alexander Kurilshikov, Arnau Vich Vila, Urmo Võsa, Zlatan Mujagic, Ad A. M. Masclee, Daisy M. A. E. Jonkers, Marije Oosting, Leo A. B. Joosten, Mihai G. Netea, Lude Franke, Alexandra Zhernakova, Jingyuan Fu, Cisca Wijmenga, Mark I. McCarthy
Journal: Nature Genetics (2019)
Local control following stereotactic body radiotherapy to adrenal oligometastases.
Authors: Nicholas B Figura, Daniel Eli Oliver, Peter Anthony Johnstone, Sarah E. Hoffe, Jessica Frakes
Journal: Journal of Clinical Oncology (2019)

447 Background: The role and associated risks of stereotactic body radiotherapy (SBRT) for adrenal metastases remain unclear. We report our single institution experience and report novel techniques to selectively dose-escalate treatment while concurrently minimizing dose to nearby critical structures. Methods: We retrospectively reviewed patients with evidence of metastatic adrenal disease originating from any primary histology treated with SBRT from 2013 to 2018. The primary endpoint was local control (LC). Secondary endpoints were disease-free survival (DFS), overall survival (OS), and treatment-related toxicity. LC, DFS, and OS were calculated with Kaplan-Meier analysis. Univariable and multivariable analysis were performed with long-rank and Cox proportional analysis. Results: A total of 45 adrenal metastases in 41 patients received SBRT. The median age was 67 years (range 40-80). The most common primary histologies were non-small cell lung cancer (51%), renal cell carcinoma (24%), and small cell lung cancer (10%). The median gross internal and planned target volumes were 21.23cc (range, 3.1–124.7cc) and 31.68cc (range, 5.2–175.9cc), respectively. The median dose administered was 50 Gy with 30 (67%) lesions receiving ≥50 Gy and 14 (31%) receiving 60 Gy. Twenty-six (58%) lesions were selectively dose-painted. Of the 42 simulations, 26 (62%) were treated supine, 5 (12%) prone, and 11 (26%) in the left lateral decubitus position. At a median follow-up of 10.5 months, there were 3 local recurrences (LR). 12-month LC rate was 96% with a median LC of 35 months. All three LR were in the metachronous, oligometastatic patients. One patient developed a hypertensive crisis which required intravenous antihypertensives. Conclusions: Adrenal SBRT for oligometastatic disease is a reasonable, noninvasive option with excellent LC and minimal toxicity. Lesions in close proximity to radiosensitive organs may benefit from techniques, such as dynamic patient positioning and selective dose-painting, for further dose-escalation to optimize LC rates while simultaneously limiting associated toxicity risks.
Royal college is under fire for “GP bashing” at conference
Authors: Abi Rimmer
Journal: BMJ (2019)

GPs have criticised the Royal College of Obstetricians and Gynaecologists (RCOG) after a medical student revealed that a speaker at one of its events had denigrated general practice.

On 9 February Shamarah Mathurin-Charles attended a medical student event run by the RCOG and the British Undergraduate Society for Obstetrics and Gynaecology. Afterwards she tweeted, “Can someone let doctors know that they don’t have to talk down on GP [general practice] to promote their own specialty?”

She added, “I’ve come to this event to learn more about a career in obstetrics and gynaecology, not to hear about how ‘GP is the easy way out’ and how people could’ve ‘just been a GP’ . . . …
Malaria in Eritrean migrants newly arrived in seven European countries, 2011 to 2016
Authors: Klara Sondén, Thierry Rolling, Andreas Wångdahl, Elsie Ydring, Sabine Vygen-Bonnet, Robert Kobbe, Johan Douhan, Ulf Hammar, Janneke Duijster, Brechje de Gier, Joanne Freedman, Nicole Gysin, Klaus Stark, Flora Stevens, Lasse Skafte Vestergaard, Anders Tegnell, Anna Färnert
Journal: Eurosurveillance (2019)

Global migration has resulted in a large number of asylum applications in Europe. In 2014, clusters of Plasmodium vivax cases were reported among newly arrived Eritreans. This study aimed to assess malaria among Eritrean migrants in Europe from 2011 to 2016. We reviewed European migration numbers and malaria surveillance data for seven countries (Denmark, Germany, Netherlands, Norway, Sweden, Switzerland and the United Kingdom) which received 44,050 (94.3%) of 46,730 Eritreans seeking asylum in Europe in 2014. The overall number of malaria cases, predominantly P. vivax, increased significantly in 2014 compared to previous years, with the largest increases in Germany (44 P. vivax cases in 2013 vs 294 in 2014, p < 0.001) and Sweden (18 in 2013 vs 205 in 2014, p < 0.001). Overall, malaria incidence in Eritreans increased from 1-5 to 25 cases per 1,000, and was highest in male teenagers (50 cases/1,000). In conclusion, an exceptional increase of malaria cases occurred in Europe in 2014 and 2015, due to rising numbers of Eritreans with high incidence of P. vivax arriving in Europe. Our results demonstrate potential for rapid changes in imported malaria patterns, highlighting the need for improved awareness, surveillance efforts and timely healthcare in migrants.
Abstract 19136: Association of Smoking With Myocardial Injury and Clinical Outcome in Patients Undergoing Mechanical Reperfusion for ST-Elevation Myocardial Infarction: Insights From Cardiovascular Magnetic Resonance Imaging
Authors: Ingo Eitel, Sebastian Reinstadler, Charlotte Eitel, Georg Fuernau, Suazanne de Waha, Steffen Desch, Holger Thiele
Journal: Circulation (2015)

Introduction: There is evidence suggesting a positive effect of cigarette smoking on myocardial tissue reperfusion and clinical outcomes in patients with myocardial infarction (“smoker’s paradox”). Hypothesis/Aim: We aimed to evaluate the relationship of smoking status with cardiac magnetic resonance (CMR)-determined myocardial salvage and damage as well as clinical outcome in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). Methods: This multicenter study included 727 consecutive STEMI patients reperfused within 12 hours after symptom onset. CMR imaging parameters (area-at-risk [AAR], infarct size [IS], myocardial salvage index [MSI], and microvascular obstruction [MVO]) were compared according to admission smoking status. Major adverse cardiac events (MACE) rates at 12 months after infarction were compared between groups. Results: In our study cohort 339 (46.6%) patients were current smokers. There was no difference in the extent of AAR (35[24-47] vs. 37[27-49] %LV, p=0.10), IS (16[8-25] vs. 17[10-26] %LV, p=0.21), MSI (53[29-70] vs. 52[34-71], p=0.47) or MVO (0[0-1.7] vs. 0[0-1.6] %LV, p=0.91) between smokers and non-smokers. Smokers had lower MACE (3.8% vs. 8.2%, p=0.01) and mortality (0.9% vs. 3.9%, p=0.01) rates. However, after adjustment for differences in baseline risk factors, smoking was no longer associated with MACE (HR=0.72, 95% CI 0.37 to 1.41, p=0.34) or mortality (HR=0.49, 95% CI 0.14 to 1.76, p=0.27). Conclusion: Smoking is not associated with PPCI efficacy (myocardial salvage) or irreversible myocardial damage in patients with acute STEMI. The lower MACE and mortality rates of smokers were entirely explained by differences in baseline risk characteristics, thus challenging the existence of a “smoker’s paradox”.
Dupilumab Improves Outcomes of Concurrent Asthma and Chronic Sino-Nasal Conditions in Patients With Atopic Dermatitis—a Pooled Analysis of Four Phase 3 Studies (LIBERTY AD SOLO 1 &amp; 2, CHRONOS, and CAFÉ)
Authors: Mark Boguniewicz, Diamant Thaçi, Peter A. Lio, Thomas Hultsch, Ana B. Rossi, Laurent Eckert, Abhijit Gadkari, Brad Shumel, Qiuyue Chen, Zhen Chen, Marius Ardeleanu
Journal: Journal of Allergy and Clinical Immunology (2019)
Nodal retrieval and short-term outcomes of robotic and laparoscopic colectomies for colon cancer.
Authors: Trang Nguyen, Stacey Stern, Ahmed Dehal, Brooke Vuong, Anton J. Bilchik
Journal: Journal of Clinical Oncology (2019)

713 Background: It is debatable whether robotic colectomies is advantageous over laparoscopic colectomies for colon cancer (CC). We aim to evaluate oncologic and perioperative outcomes between robotic and laparoscopic colectomies in a national database. Methods: The National Cancer Database was queried from 2010-2014 for patients with resectable (stage I-III) CC. Lymph node (LN) retrieval, length of stay (LOS), perioperative outcomes and OS were analyzed based on type of surgery: right colectomy vs. left colectomy and robotic (ROBO) vs. laparoscopic (LAP). Results: 61,903 patients met inclusion criteria. There was no difference in inadequate LN retrieval (&lt; 12 LN), or short-term mortality between ROBO and LAP groups. There was a significant decrease in conversion to an open operation and LOS for ROBO vs. LAP groups as well as increased 5 year OS (Table). ROBO colectomies increased four-fold over 5 years. About half were done at community hospitals (56%) and at low ROBO volume hospitals (47.2%). Inadequate LN retrieval in the ROBO group was greater at low volume centers (9.2%) compared to high volume centers (12.3%) (p &lt; 0.0001) as well as at community hospitals (12.2%) compared to academic hospitals (8.5%) (p=0.0003). Conclusions: This population analysis showed that robotic colectomies was associated with equivalent short-term outcomes and LN retrieval as laparoscopic colectomies. However, half of robotic colectomies were done at community hospitals or low volume hospitals, where the rate of inadequate LN retrieval was higher than at academic hospitals or high volume centers. As robotic colectomies increases, it is important that technology is implemented judiciously so that oncologic outcomes are not compromised. [Table: see text]
Are there distinct clinical and pathological features distinguishing idiopathic from drug-induced subacute cutaneous lupus erythematosus? A European retrospective multicenter study
Authors: Federica Guicciardi, Laura Atzori, Angelo Valerio Marzano, Simona Tavecchio, Giampiero Girolomoni, Chiara Colato, Axel Patrice Villani, Jean Kanitakis, Christina Mitteldorf, Rosanna Satta, Bernard Cribier, Laurence Gusdorf, Maria Teresa Rossi, Piergiacomo Calzavara-Pinton, Isabel Bielsa, Maria Teresa Fernandez-Figueras, Werner Kempf, Giorgio Filosa, Luca Pilloni, Franco Rongioletti
Journal: Journal of the American Academy of Dermatology (2019)
A central review of liver resectability and pathological tumor response after chemotherapy in patients with initially unresectable colorectal cancer liver metastases: Phase II trials of mFOLFOX6 plus bevacizumab (KSCC0802), and SOX (S-1 and oxaliplatin) plus cetuximab (KSCC1002).
Authors: Eiji Oki, Yasunori Emi, Hiroshi Saeki, Shoji Tokunaga, Toru Beppu, Ken Shirabe, Mitsuhisa Takatsuki, Shinji Uchida, Masahiko Sakoda, Susumu Eguchi, Masafumi Inomata, Yoshito Akagi, Shoji Natsugoe, Yutaka Ogata, Yoshihiro Kakeji, Hideo Baba, Kenichi Iyama, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2015)

e14548 Background: We conducted a central review of liver resectability and pathological response for two Phase II trials for initially unresectable, or not optimally resectable, colorectal cancer liver metastases (CRLM). In the KSCC0802 trial, 40 patients with unresectable CRLM (ASCO 2012 abs 666) were included from a multicenter trial of modified FOLFOX6 plus bevacizumab (mFOLFOX6 + Bmab). In the KSCC1002 trial, 33 KRASwild-type patients with unresectable CRLM (ASCO-GI 2015 abs 755) were included from a trial of SOX (S-1 and oxaliplatin) plus cetuximab (SOX + Cmab). Methods: Five independent liver surgeons evaluated the liver resectability based on the analyses of contrast-enhanced computed tomography images made after the protocol-defined treatment of all patients. In the cases of liver resected patients, pathological responses were evaluated according to the following criteria: grade 0: no necrosis; grade 1a: the presence of necrosis or the disappearance of <1/3 of the entire tumor; grade 1b: the presence of necrosis or the disappearance of <2/3 of the entire tumor; grade 2: the presence of necrosis or the disappearance of >2/3 of the entire tumor; and grade 3: the entire tumor presenting necrosis. Results: In the KSCC0802 trial, a central review showed that 36.1% of the LM were resectable at baseline while 47.2% (an 11.1% increase) were resectable after chemotherapy. In the KSCC1002 trial, 18.2% of liver metastases were resectable at baseline, whereas 66.7% (a 48.5% increase) were resectable after chemotherapy. However, a pathological review showed a higher grade of tumor pathological response in the KSCC0802 trial than in the KSCC1002 trial. Conclusions: High tumor shrinkage mediated by SOX plus cetuximab led to high resectability for CRLM, but it may not lead to a favorable pathological response. Clinical trial information: UMIN000001308, UMIN000004331.Central review of pathological response. Histological response KSCC0802 (mFOLFOX6 + Bmab) KSCC1002 (SOX + Cmab) n = 16 % n = 16 % Grade 0 1 6.3 0 0 Grade 1a 2 12.5 9 56.3 Grade 1b 4 25.0 2 12.5 Grade 2 7 43.8 4 25.0 Grade 3 0 0 1 6.3 not done 2 12.5 0 0
Unscrambling the evidence for breakfast
Authors: Tom Moberly
Journal: BMJ (2019)

The first thing Winnie-the-Pooh asks himself every morning is “What’s for breakfast?” When Piglet says that he starts the day by wondering, “What’s going to happen exciting today,” Pooh nods thoughtfully and replies, “It’s the same thing.”

I’m of much the same mind, and I should declare that as an interest right now. I love breakfast, and I eat it every day without fail. I’m certainly not alone in this, and many people argue that breakfast is not only …
Intuitive vs Deliberative Approaches to Making Decisions About Life Support
Authors: Emily B. Rubin, Anna E. Buehler, Elizabeth Cooney, Nicole B. Gabler, Adjoa A. Mante, Scott D. Halpern
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Patients with serious illnesses are often encouraged to actively deliberate about the desirability of life support. Yet it is unknown whether deliberation changes the substance or quality of such decisions. <h3>Objective</h3> To identify differences in decisions about life support interventions and goals of care made intuitively vs deliberatively by patients with serious illnesses. <h3>Design, Setting, and Participants</h3> Randomized clinical trial in which patients were asked to express treatment preferences in a series of clinical scenarios. Participants were 199 hospitalized patients aged 60 years and older with serious oncologic, cardiac, and pulmonary illnesses treated in a large, urban academic hospital from July 1, 2015, through March 15, 2016. <h3>Interventions</h3> Patients in the intuitive group were subjected to a cognitive load and instructed to answer each question immediately based on gut instinct. Patients in the deliberative group were not cognitively loaded, were instructed to think carefully about their answers, and were required to explain their answers. <h3>Main Outcomes and Measures</h3> Choices regarding life support (4 scenarios) and goals of care (1 scenario), concordance of these choices with patients' valuations of health states that could follow from them, and decisional uncertainty. <h3>Results</h3> Of 199 patients, 132 (66%) were male and the mean (SD) age was 67.2 (5.0) years. Similar proportions of patients in the intuitive group (n = 97) and the deliberative group (n = 102) said they would accept a feeding tube for chronic aspiration (42% vs 44%, respectively; difference, −2%; 95% CI, −16% to 12%;<i>P</i> = .79), antibiotics for life-threatening infection in the event of terminal illness (39% vs 43%, respectively; difference, −4%; 95% CI, −18% to 10%;<i>P</i> = .57), a trial of mechanical ventilation (59% vs 60%, respectively; difference,−1%; 95% CI, −15% to 13%;<i>P</i> = .88), and a tracheostomy tube (37% vs 41%, respectively; difference, −4%; 95% CI, −22% to 13%;<i>P</i> = .64). Patients in the deliberative group were slightly more likely than patients in the intuitive group to choose a palliative approach to treatment in the event of serious illness (45% vs 30%, respectively; difference, 15%; 95% CI, 1%-29%;<i>P</i> = .04). Across scenarios, decisional uncertainty was similar between the 2 groups (all<i>P</i> &gt; .05), and intuitive decisions were either equally or more closely aligned with patients' health state valuations than deliberative decisions. <h3>Conclusions and Relevance</h3> In this study, encouraging hospitalized patients with serious illnesses to deliberate on end-of-life decisions did not change the content or improve the quality of these decisions. It is important to evaluate whether decision aids and structured communication interventions improve seriously ill patients' choices. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02487810