tbuckley/cabot-search huggingface dataset:
Abstract P5-16-16: Reconstructive breast surgery with partially absorbable bi-component Seragyn® BR soft mesh: An outcome analysis
Authors: A Machleidt, N Schmidt-Feuerheerd, J-U Blohmer, R Ohlinger, J Küper, G von Waldenfels, S Dittmer, S Paepke, E Klein
Journal: Cancer Research (2019)

Abstract Objective: Synthetic meshes and acellular dermal matrices are increasingly used in implant based breast reconstruction. The objective of this study was to determine the incidence and severity of complications following the implantation of the partially absorbable bi-component soft mesh SERAGYN ® BR and assess risk factors for adverse operative outcomes. Methods: A retrospective clinical study was performed: The SERAGYN ® BR soft mesh was utilized in 148 operations (skin-sparing mastectomy, nipple-sparing mastectomy, breast conserving surgery, secondary reconstruction after mastectomy) in four different institutions in Germany from June 2012 to February 2014. We analyzed whether the results were affected by tumor morphology (e.g. grading), patient characteristics and co-morbidities, previous surgery or therapies and use of alloplastic materials. Results: The SERAGYN ® BR soft mesh was successfully implanted in 131 of 148 operations. The rate of reconstructive failure was 11.5 %. The most common complication was seroma (25.7 %), followed by hematoma and skin infection (each 14.2%). Wound healing issues were detected in 13.5% cases, secondary wound infections in 10.8%. 83.8% of operations had no severe complications. Independent predictors for reconstructive failure were wound healing issues, nipple- or skin necrosis, wound- or skin infections, a high volume of excised tissue, hematomas, seromas and sentinel lymph node excisions. A higher body mass index was correlated with a higher rate of infection. Conclusion: SERAGYN ® BR mesh can be used successfully in breast reconstructive surgery. Rates of major complications or reconstructive failure are comparable to the use of other synthetic or biological meshes. Citation Format: Machleidt A, Schmidt-Feuerheerd N, Blohmer J-U, Ohlinger R, Küper J, von Waldenfels G, Dittmer S, Paepke S, Klein E. Reconstructive breast surgery with partially absorbable bi-component Seragyn® BR soft mesh: An outcome analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-16.
Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations
Authors: Christian Mueller, Kenneth McDonald, Rudolf A. de Boer, Alan Maisel, John G.F. Cleland, Nikola Kozhuharov, Andrew J.S. Coats, Marco Metra, Alexandre Mebazaa, Frank Ruschitzka, Mitja Lainscak, Gerasimos Filippatos, Petar M. Seferovic, Wouter C. Meijers, Antoni Bayes‐Genis, Thomas Mueller, Mark Richards, James L. Januzzi
Journal: European Journal of Heart Failure (2019)
Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial
Authors: Leonie Voorwerk, Maarten Slagter, Hugo M. Horlings, Karolina Sikorska, Koen K. van de Vijver, Michiel de Maaker, Iris Nederlof, Roelof J. C. Kluin, Sarah Warren, SuFey Ong, Terry G. Wiersma, Nicola S. Russell, Ferry Lalezari, Philip C. Schouten, Noor A. M. Bakker, Steven L. C. Ketelaars, Dennis Peters, Charlotte A. H. Lange, Erik van Werkhoven, Harm van Tinteren, Ingrid A. M. Mandjes, Inge Kemper, Suzanne Onderwater, Myriam Chalabi, Sofie Wilgenhof, John B. A. G. Haanen, Roberto Salgado, Karin E. de Visser, Gabe S. Sonke, Lodewyk F. A. Wessels, Sabine C. Linn, Ton N. Schumacher, Christian U. Blank, Marleen Kok
Journal: Nature Medicine (2019)
Pneumocystosis pneumonia: A comparison study between HIV and non-HIV immunocompromised patients
Authors: I. Rego de Figueiredo, R. Vieira Alves, D. Drummond Borges, M. Torres, F. Lourenço, A.M. Antunes, H. Gruner, A. Panarra
Journal: Pulmonology (2019)

Pneumocystis pneumonia (PCP) is caused by the fungus Pneumocystis jirovecii, and its incidence has been on the rise in immunosuppressed patients without HIV. We performed a cross sectional study in patients with PCP and assessed demographic, clinical presentation and outcome measures such as mechanical ventilation and mortality differences between HIV and non-HIV patients. The two groups were statistically significantly different, with the HIV group being younger (45.5 years vs 55.9 years, p-value 0.001) and mostly composed of male patients (69% vs 31%, p-value <0.001). Also, the HIV patients had higher percentage of respiratory complaints (90% vs 68%, p-value 0.02) and lactate dehydrogenase elevation (73% vs 40%, p-value 0.001). In contrast, non-HIV patients had worse outcomes with higher incidence of invasive mechanical ventilation (23% vs 46%, p-value 0.005) and in-hospital mortality (13% vs 37%, p-value 0.002). These results reflect the literature and should raise awareness to a potentially fatal medical situation of increasing incidence.
Abstract P1-17-08: High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study
Authors: F Recchia, G Candeloro, S Rea
Journal: Cancer Research (2019)

Abstract Background: PBC+10N have a high risk of relapse. Experimental studies suggest that high expression of vascular endothelial growth factor (VEGF) promotes tumor progression through neoangiogenesis and that natural killer (NK) cells mediate lytic activity against cancer cell lines. In a phase I-II study, we have shown that low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) increased NK cells and decreased VEGF, in patients with advanced cancer and a clinical benefit from chemotherapy (Clin Cancer Res 7: 1251, 2001). We assumed that IL-2 and RA, increasing NK and decreasing VEGF, could improve disease-free survival (DFS) and overall survival (OS) in PBC+10N. Primary endpoint was the evaluation of NK cells and VEGF; secondary endpoints were DFS, OS and toxicity. Methods: 34 patients with PBC+10N, after high-dose chemotherapy and peripheral blood progenitor cell transplantation were entered into the study. They were given hormonal therapy if needed and subcutaneous IL-2, 1.8 X 106 IU and oral RA, 0.5 mg/Kg for 5 days/week, 3 weeks/month, until progression. NK cells, VEGF, response and toxicity were assessed every 4 months. Results: After a median follow-up of 120 months (range 69-209), a total of 41 courses of high-dose chemotherapy and 60 courses of immunotherapy were delivered. A statistically significant improvement of NK cells [from a mean of 302 ± 75/mm3 to a mean of 582 ± 72/mm3 (p &amp;lt; 0.001)] and a decrease of VEGF [from a mean of 525 ± 68 pg/mm3 to a mean of 155 ± 13 pg/mm3, (p &amp;lt; 0.001)], were observed. 18-years DFS and OS were 29% and 32%, respectively. A significant improvement, with respect to NCI SEER data (*), was observed in the 5-year OS rate: 55% vs. 6% No WHO grade 3 or 4 toxicity was observed, while grade 2 cutaneous toxicity and fever occurred in 20% and 13% of patients, respectively. Conclusions: Our data show that immunotherapy with IL-2/RA, may determine, with an acceptable toxicity profile, a statistically significant improvement of NK cells, a decrease of VEGF, and better 5-year survival rates with respect to NCI SEER data. Citation Format: Recchia F, Candeloro G, Rea S. High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-08.
Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data
Authors: Lex W Doyle, Sture Andersson, Andy Bush, Jeanie L Y Cheong, Hege Clemm, Kari Anne I Evensen, Aisling Gough, Thomas Halvorsen, Petteri Hovi, Eero Kajantie, Katherine J Lee, Lorcan McGarvey, Indra Narang, Pieta Näsänen-Gilmore, Sigurd Steinshamn, Maria Vollsaeter, Elianne J L E Vrijlandt
Journal: The Lancet Respiratory Medicine (2019)
Planning my career in a climate of change
Authors: Caroline Elton
Journal: BMJ (2016)

#### Dear Caroline

Many changes are proposed for the NHS—what advice can you give for making career choices when the climate seems so unpredictable?

Jilna Shukla, currently on F3 and F4 year out, based in the United Kingdom

The only constant in medical training is change. When I first started working in medical education back in 1998, the major change du jour was the creation of specialty registrar posts. Since then we have had the Modernising Medical Careers reforms, the introduction of the European Working Time …
Is it possible to take a complete break from clinical work after foundation training?
Authors: Caroline Elton
Journal: BMJ (2018)

Dear Caroline

I want to take a complete break from clinical work for a year after foundation training. Is this possible, and how would it look on my application for specialty training? 



New foundation year 1 trainee

Each year the UK Foundation Programme Office publishes a destination report. Back in 2011, more than 70% of foundation year 2 trainees went straight into a specialty training programme in the United Kingdom. The latest figures (for 2015), however, show that the figure has dropped to 52%. In other words, last year nearly half the foundation year 2 doctors …
Increase in Hepatitis A Virus Infections — United States, 2013–2018
Authors: Monique A. Foster, Megan G. Hofmeister, Benjamin A. Kupronis, Yulin Lin, Guo-Liang Xia, Shaoman Yin, Eyasu Teshale
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Hepatitis A virus (HAV) is primarily transmitted fecal-orally after close contact with an infected person (1); it is the most common cause of viral hepatitis worldwide, typically causing acute and self-limited symptoms, although rarely liver failure and death can occur (1). Rates of hepatitis A had declined by approximately 95% during 1996-2011; however, during 2016-2018, CDC received approximately 15,000 reports of HAV infections from U.S. states and territories, indicating a recent increase in transmission (2,3). Since 2017, the vast majority of these reports were related to multiple outbreaks of infections among persons reporting drug use or homelessness (4). In addition, increases of HAV infections have also occurred among men who have sex with men (MSM) and, to a much lesser degree, in association with consumption of imported HAV-contaminated food (5,6). Overall, reports of hepatitis A cases increased 294% during 2016-2018 compared with 2013-2015. During 2016-2018, CDC tested 4,282 specimens, of which 3,877 (91%) had detectable HAV RNA; 565 (15%), 3,255 (84%), and 57 (<1%) of these specimens were genotype IA, IB, or IIIA, respectively. Adherence to the Advisory Committee on Immunization Practices (ACIP) recommendations to vaccinate populations at risk can help control the current increases and prevent future outbreaks of hepatitis A in the United States (7).
Advice on funding your medical degree
Authors: Christian Bodden
Journal: BMJ (2017)

An overview of the funding you are entitled to and what to do if you fall into financial difficulty Studying medicine can be expensive, and many students worry about whether they will have enough money to fund their studies and cover basics such as food and rent, despite funding from national student loans companies and the NHS student bursary. In 2013, a survey of 2735 UK medical students conducted by Cardiff University on behalf of the General Medical Council explored the factors that affect the wellbeing of medical students. It found that “finance was found to be a significant area of concern raised by students in the focus groups.”1 And in 2012, a survey by the BMA, which received 623 responses, found that money worries were having a negative impact on students’ stress levels (68%), quality of life (64%), quality of academic work (36%), and dedication to medicine (22%).2 This article provides an overview of the funding you are entitled to, how to plan your finances, and what to do if things go wrong if you are studying in the UK. Costs vary, but the following are things to consider budgeting for each year:
Abstract P5-05-13: Quantitative combinatory indexed ChIP-seq reveals distinct transcriptional complexes containing estrogen receptor and GREB1 at chromatin in breast cancer cells
Authors: J Sun, ME Lippman
Journal: Cancer Research (2019)

Abstract GREB1 is an estrogen-activated gene in estrogen receptor a (ER)-positive breast cancer cells. GREB1 is also required for estrogen-stimulated breast cancer cell growth and its level is highly correlated to ER level in breast cancer cells and tumor samples. In endocrine resistant diseases, GREB1 is often dysregulated. GREB1 has been shown to interact with ER and bind to the same ER binding sites throughout the genome. There is no identified functional domain in GREB1 and it is not completely known how GREB1 exerts its function to regulate the transcription of ER target genes. In order to demonstrate whether GREB1 is present in the ER-containing transcriptional complex at chromatin, we have adapted and developed a quantitative combinatory indexed ChIP-seq assay suitable for dissecting components in a transcriptional cofactor complex in a genome-wide scale. In ER-positive MCF-7 breast cancer cells, we found that almost all GREB1 binding sites are the same sites bound by ER or its bona fide coactivator SRC-3. We further found that GREB1 and SRC-3 are both present in the same ER-containing complex at chromatin. Thus, both GREB1 and SRC-3 are integral members of the ER transcriptional complex at chromatin. Moreover, we discovered that only a portion of GREB1 at chromatin is present in the ER complex while the other portion of GREB1 is present in a different complex lacking ER or SRC-3 at the same genomic loci. Thus, two distinct GREB1-containing complexes are identified in equilibrium at chromatin: one contains ER/SRC-3 and the other one lacks ER/SRC-3. Our results suggest a non-traditional role of GREB1 in transcriptional regulation of ER target genes. The method used in our study can be widely applied for probing components of transcriptional complexes at chromatin. Citation Format: Sun J, Lippman ME. Quantitative combinatory indexed ChIP-seq reveals distinct transcriptional complexes containing estrogen receptor and GREB1 at chromatin in breast cancer cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-05-13.
Colorectal endoscopic submucosal dissection using “mucosal bridges” for local recurrence after endoscopic resection
Authors: Shunsuke Yoshii, Yoshito Hayashi, Yoshiki Tsujii, Hideki Iijima, Tetsuo Takehara
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) for local recurrence after endoscopic resection can be challenging because of diffuse submucosal fibrosis. Although the pocket-creation method (PCM) is very useful to overcome submucosal fibrosis during colorectal ESD [1] [2] [3], identifying the dissecting line amidst diffuse fibrotic submucosa is difficult because the edge of the resected specimen is invisible from inside the pocket. Here, we present a novel strategy for performing ESD using mucosal bridges ([Fig. 1], [Video 1]).
Making the hospital work for you: record keeping
Authors: James Smith, Francesca Flohr, Anusha Edwards
Journal: BMJ (2011)

The first in a series of articles takes you from how to hand over to how to discharge patients appropriately The UK General Medical Council states that doctors must “keep clear, accurate and legible records reporting relevant clinical findings.”1 This comes after decades of poor handwriting and documentation leading to patient morbidity and mortality and substantial cost to the economy. In 1999 a cardiologist and pharmacist received a combined fine of $450 000 (£287 000; €329<thin<000) after the death of a patient. A poorly written prescription had been interpreted as Plendil (felodipine), rather than Isordil (isosorbide dinitrate).2 This highlights the fact that accurate record keeping and patient documentation are essential in medical practice, but they are not always well taught. Junior doctors are assumed to be familiar with the basic fundamental practice of record keeping and the care needed in data protection. Although these may seem simple practices, they are rarely done well. Box 1 and figure 1 give several helpful tips for record keeping.⇓ #### Box 1: Tips for record keeping It is worth thinking about the most accurate and succinct way of documenting your thoughts. They can be written as bullet points or in prose. With all record keeping some essential points must always be practised.
Scaffolds biomimicking macrophages for a glioblastoma NIR-Ib imaging guided photothermal therapeutic strategy by crossing Blood-Brain Barrier
Authors: Jiazheng Lai, Guanjun Deng, Zhihong Sun, Xinghua Peng, Jing Li, Ping Gong, Pengfei Zhang, Lintao Cai
Journal: Biomaterials (2019)
Universal Tumor DNA BRCA1/2 Testing of Ovarian Cancer: Prescreening PARPi Treatment and Genetic Predisposition
Authors: Janet R Vos, Ingrid E Fakkert, Joanne A de Hullu, Anne M van Altena, Aisha S Sie, Hicham Ouchene, Riki W Willems, Iris D Nagtegaal, Marjolijn C J Jongmans, Arjen R Mensenkamp, Gwendolyn H Woldringh, Johan Bulten, Edward M Leter, C Marleen Kets, Michiel Simons, Marjolijn J L Ligtenberg, Nicoline Hoogerbrugge, Inge M W Ebisch, Ineke M de Kievit, Nicole G Laurens, Nelleke Ottevanger, Robbert J van Alphen, M Caroline Vos, Anneke A M van den Wurff, Roel van Kampen, Helen J M M Mertens, Prapto Sastrowijoto, Mirjam J A Engelen, Roy I Lalisang, Brigitte F M Slangen, Loes F S Kooreman, Geert-Jan M Creemers, Jurgen M J Piek, Paul Klinkhamer, Judith W M Jeuken, Anette L Aalders, Riena P Aliredjo
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Women with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as a prescreen for PARPi treatment and cancer predisposition testing. Methods Formalin-fixed paraffin-embedded tissue was obtained from OC patients in seven hospitals immediately after diagnosis or primary surgery. DNA was extracted, and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated. Results Tumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients, pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% of patients. Participating gynecologists and patients were overwhelmingly positive about the workflow. Conclusions Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.
Abstract CS1-2: Breast cancer genetic testing and results in diverse populations
Authors: A Kurian
Journal: Cancer Research (2019)

Abstract Sequencing multiple (20-100) cancer-associated genes has rapidly become the clinical standard for hereditary cancer risk assessment. In patients with breast cancer and/or ovarian cancer the BRCA1 and BRCA2 genes have been most widely tested, but a significant number of patients are now found to carry pathogenic (or likely pathogenic) variants in many other genes whose cancer risks are less well-characterized. Moreover, multiple-gene sequencing is associated with a higher rate of uncertain results (variants of uncertain significance), which are more prevalent among racial/ethnic minorities. While pathogenic variants in less well-characterized genes are prevalent, the appropriate management of carriers remains unclear. Questions remain about the magnitude of risk associated with a pathogenic variant in a specific gene; the spectrum of associated cancers; and the extent to which these factors are modified by family cancer history. Data are emerging from epidemiologic studies in various settings. However, clinical practice requires real-time decisions about whom to test, and for which cancers to screen, despite an incomplete evidence base. This lecture will review the current state of the science on genetic testing for hereditary breast and ovarian cancer risk. We have recently collaborated with genetic testing laboratories to link the results of clinical genetic testing to Surveillance, Epidemiology and End Results (SEER) registry records of &amp;gt;150,000 breast cancer and/or ovarian cancer patients. I will present results from the SEER-GeneLINK research initiative, focusing on the use, correlates and outcomes of genetic testing on the population level. Citation Format: Kurian A. Breast cancer genetic testing and results in diverse populations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr CS1-2.
Abstract P1-02-08: Withdrawn
Authors: C Ellsworth Beaumont, E Nwankwo
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Ellsworth Beaumont C, Nwankwo E. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-02-08.