tbuckley/cabot-search huggingface dataset:
Abstract P3-11-23: GDC-0077 is a selective PI3K alpha inhibitor with robust efficacy in PIK3CA mutant hormone-positive breast cancer models
Authors: Kyle Edgar, Rebecca Hong, Kyung Song, Steven Schmidt, Marc Hafner, Alfonso Arrazate, Erin Williams, Cecile De La Cruz, Jason Oeh, Deepak Sampath, Steve Staben, Lori Friedman
Journal: Cancer Research (2020)

Abstract The phosphatidylinositol 3kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of tumor cell growth, proliferation and survival. Hotspot mutations of PIK3CA are common in all subtypes of breast cancer with a prevalence of approximately 30%. GDC-0077 is a potent ATP-competitive inhibitor of PI3K alpha (IC50 = 0.038 ± 0.003 nM), thereby inhibiting the phosphorylation of membranebound PIP2 to PIP3. Biochemically, GDC-0077 is more than 300fold selective over the other Class I PI3K isoforms, beta, delta, and gamma, and more than 2000-fold more selective over PI3K class II and III family members. Importantly, GDC-0077 is more selective for mutant versus wild-type PI3K alpha in cell-based assays. Mechanism of action studies indicate that GDC-0077 treatment leads to degradation of the mutant PI3K alpha protein in a proteasome dependent fashion, without changing WT PI3K alpha levels. Drug treatment results in sustained reduction of PI3K pathway biomarkers pAkt and pPRAS40, inhibition of cell proliferation, and increased apoptosis in human PIK3CA mutant breast cancer cell lines, to a greater extent than other non-degrading inhibitors such as alpelisib. Combination studies of GDC-0077 with the CDK4/6 inhibitor palbociclib demonstrate a stronger effect in estrogen-depleted HR+ PIK3CA mutant breast cell lines, compared to cells grown in the presence of estrogen. Daily dosing of GDC-0077 in PIK3CA mutant breast cancer patient derived xenograft (PDX) models (n=4) resulted in tumor regressions, induction of apoptosis and a reduction of pAkt, pPRAS40, and pS6RP in a dose-dependent fashion. In vivo combination efficacy studies of GDC-0077 with fulvestrant and palbociclib also indicate the triple combination results in the greatest efficacy. Collectively, our preclinical data support evaluation of GDC-0077 in a triple combination with endocrine therapy and CDK4/6 inhibition in the clinic, in patients with locally advanced or metastatic hormone receptor positive breast cancer whose tumors harbor mutant PIK3CA. Citation Format: Kyle Edgar, Rebecca Hong, Kyung Song, Steven Schmidt, Marc Hafner, Alfonso Arrazate, Erin Williams, Cecile De La Cruz, Jason Oeh, Deepak Sampath, Steve Staben, Lori Friedman. GDC-0077 is a selective PI3K alpha inhibitor with robust efficacy in PIK3CA mutant hormone-positive breast cancer models [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-23.
Terbinafine and Fulminant Hepatic Failure
Authors: Kosh Agarwal, Derek M. Manas, Mark Hudson
Journal: New England Journal of Medicine (1999)

To the Editor: Terbinafine is an antifungal agent that is widely prescribed for common skin infections.1 We describe a patient who had taken terbinafine and in whom fulminant hepatic failure develo...
Candida auris: epidemiological situation, laboratory capacity and preparedness in the European Union and European Economic Area*, January 2018 to May 2019
Authors: Diamantis Plachouras, Felix Lötsch, Anke Kohlenberg, Dominique L Monnet
Journal: Eurosurveillance (2020)

Between January 2018 and May 2019, 349 cases of Candida auris were reported in the European Union/European Economic Area*, 257 (73.6%) colonisations, 84 (24.1%) bloodstream infections, seven (2.0%) other infections and one case of unknown infection/colonisation status (0.3%). Most cases (97.1%, n = 339) were reported from Spain or the United Kingdom, but also for the first time in Greece, the Netherlands and Poland. Laboratory capacity and preparedness has improved since January 2018.
Nonfatal Violent Workplace Crime Characteristics and Rates by Occupation — United States, 2007–2015
Authors: Miriam Siegel, Candice Y. Johnson, Christina C. Lawson, Marilyn Ridenour, Daniel Hartley
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Approximately eight nonfatal violent workplace crimes were reported per 1,000 U.S. workers during 2007–2015; 58% of crimes were not reported to police. Highest rates of crime were among protective services, community and social services, and health care occupations.
Validity of daily self-pulse palpation for atrial fibrillation screening in patients 65 years and older: A cross-sectional study
Authors: Faris Ghazal, Holger Theobald, Mårten Rosenqvist, Faris Al-Khalili
Journal: PLoS Medicine (2020)

Background The European Society of Cardiology guidelines recommend (Class IA) single-time–point screening for atrial fibrillation (AF) using pulse palpation. The role of pulse palpation for AF detection has not been validated against electrocardiogram (ECG) recordings. We aimed to study the validity of AF screening using self-pulse palpation compared with an ECG recording conducted at the same time using a handheld ECG 3 times a day for 2 weeks. Methods and findings In this cross-sectional screening study, patients 65 years of age and older attending 4 primary care centers (PCCs) outside Stockholm County were invited to take part in AF screening from July 2017 to December 2018. Patients were included irrespective of their reason for visiting the PCC. Handheld intermittent ECGs 3 times per day were offered to patients without AF for a period of 2 weeks, and patients were instructed in how to take their own pulse at the same time. A total of 1,010 patients (mean age 73 years, 61% female, with an average CHA2DS2-VASc score 2.9) participated in the study, and 27 (2.7%, 95% CI 1.8%–3.9%) new cases of AF were detected. Anticoagulants (ACs) could be initiated in 26 (96%, 95% CI 81%–100%) of these cases. A total of 53,782 simultaneous ECG recordings and pulse measurements were registered. AF was verified in 311 ECG recordings, of which the pulse was palpated as irregular in 77 recordings (25%, 95% CI 20%–30% sensitivity per measurement occasion). Of the 27 AF cases, 15 cases felt an irregular pulse on at least one occasion (56%, 95% CI 35%–75% sensitivity per individual). 187 individuals without AF felt an irregular pulse on at least one occasion. The specificity per measurement occasion and per individual was (98%, 95% CI 98%–98%) and (81%, 95% CI 78%–83%), respectively. Conclusions AF screening using self-pulse palpation 3 times daily for 2 weeks has lower sensitivity compared with simultaneous intermittent ECG. Thus, it may be better to screen for AF using intermittent ECG without stepwise screening using pulse palpation. A limitation of this model could be the reduced availability of handheld ECG recorders in primary care centers.
Abstract ES5-3: Surgical considerations after preoperative therapy for hormone receptor positive breast cancer
Authors: TA King
Journal: Cancer Research (2020)

Abstract Session Title: Multidisciplinary approaches to optimize surgical therapy in hormone receptor positive breast cancer Talk Title: Surgical considerations after preoperative therapy in hormone receptor positive breast cancer Abstract: Preoperative therapy increases rates of breast conservation and decreases the need for axillary lymph node dissection (ALND) in select patients. In hormone receptor positive (HR+) HER2 negative breast cancer patients the choice between neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy (NET) to achieve breast conservation can be challenging and the low rates of axillary pCR with either approach have been associated with higher rates of ALND. For HR+ HER2- patients receiving NAC, available literature supports performing sentinel lymph node biopsy (SLNB) after receipt of therapy with the decision to perform axillary lymph node dissection dictated by the status of the sentinel lymph nodes. For patients receiving NET, there is little data to guide surgical management of the axilla. In a recent review of the NCDB, we assessed axillary management by initial treatment strategy (NET, NAC, or upfront surgery) among a large population of Stage II-III HR+ HER2- breast cancer patients and found that SLNB use after NET in both clinically node negative and clinically node positive patients was similar to SLNB use with upfront surgery. However, among those with pN1 disease, patients who received NET were less likely to undergo ALND. While failure to achieve a nodal pCR after NAC is associated with inferior DFS and OS outcomes; whether or not the same is true after NET remains uncertain. Further, the impact of residual nodal disease after NET on LRR remains an area of ongoing investigation. Understanding the differences in and implications of residual nodal disease after neoadjuvant therapy (NAC vs NET) in HR+ HER2- breast cancer provides the opportunity to develop subtype specific strategies for optimal surgical management of the axilla. Citation Format: TA King. Surgical considerations after preoperative therapy for hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES5-3.
Incidence of New Coronary Calcification
Authors: Omar Dzaye, Zeina A. Dardari, Miguel Cainzos-Achirica, Ron Blankstein, Moyses Szklo, Matthew J. Budoff, Joao A.C. Lima, Roger S. Blumenthal, Khurram Nasir, Michael J. Blaha
Journal: Journal of the American College of Cardiology (2020)
Abstract 107: Cardiac Arrest Outcomes After Target Temperature Management With an Esophageal Cooling Device
Authors: Marvin A Wayne, Cedar Anderson, Rick Fisher, Donald Berry, J.Brad Diestelhorst
Journal: Circulation (2019)

Introduction: Optimal patient care after cardiac arrest includes targeted temperature management (TTM). Methods typically utilized for patient temperature control, including ice-packs, servo-controlled surface pads, and intravascular catheters. A new device placed in the esophagus that cools from the patient’s core may offer advantages over other methods. It avoids risks from intravascular catheters, reduces shivering from surface contact, and allows core temperature control to be rapidly performed, after placement, by nursing staff. Hypothesis: Using a nurse driven protocol we sought to quantify patient outcomes, after TTM, using an esophageal device, in our mixed-population intensive care unit. Methods: We reviewed the charts of all patients treated with esophageal TTM as part of our standard post-arrest bundle at our advanced community medical center. We recorded patient age, gender, target temperature, TTM initiation time, the time goal temperature was attained, and patient survival. Results: A total of 54 patients were treated with esophageal TTM over the study period, from August 2016 to November 2018. Of these 2 recovered and had treatment discontinued prior to reaching target, leaving 52 for analysis (19 female, 33 male, age 18-79, median age 62.5). Nurses placed all ETM devices, and target temperatures varied by clinician preference, from 32°C to 36°C. Survival to ICU discharge was 51.9% for the entire cohort, with male survival (61%) greater than female (37%), p=0.10; however, Cfor the entire cohort was 219 minutes (IQR 81-415). Survivors exhibited longer times to achieve goal temperature (median 180 minutes in non-survivors vs. 255 minutes in survivors). Conclusions: Esophageal TTM offers a nurse-driven approach to obtain rapid core temperature management, with good outcomes in our patient population. As seen elsewhere, surviving patients require longer times to reach target temperature.
Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8+ T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma
Authors: Jossie Rotman, A. Marijne Heeren, Awa A. Gassama, Sinead M. Lougheed, Noëlle Pocorni, Anita G.M. Stam, Maaike C.G. Bleeker, Henry J.M.A.A Zijlmans, Constantijne H. Mom, Gemma G. Kenter, Ekaterina S. Jordanova, Tanja D. de Gruijl
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Adenocarcinoma of the uterine cervix is the second most common type of cervical cancer after squamous cell carcinoma (SCC). Although both subtypes are treated similarly, patients with adenocarcinoma have a worse prognosis. In this study, immunologic features of the tumor microenvironment in these two subsets were pursued with potential therapeutic implications. Experimental Design: The immune microenvironment of primary tumors and nonmetastatic tumor-draining lymph nodes (TDLN) was compared between patients with cervical adenocarcinoma (n = 16) and SCC (n = 20) by polychromatic flow cytometry and by transcriptional profiling of the primary tumors (n = 299) using publicly available data from The Cancer Genome Atlas (TCGA). Results: Flow cytometric analyses revealed intact T-cell differentiation in TDLNs, but hampered effector T-cell trafficking to the primary tumors in adenocarcinoma, as compared with SCC. TCGA analysis demonstrated higher expression of chemokines involved in effector T-cell homing (CXCL9/10/11) in SCC primary tumors as compared with adenocarcinoma primary tumors, which was highly correlated to a transcriptional signature for type I conventional dendritic cells (cDC1). This was consistent with elevated frequencies of CD141/BDCA3+cDC1 in primary tumor SCC samples relative to adenocarcinoma and correspondingly elevated levels of CXCL9 and CXCL10 in 24-hour ex vivo cultures. Hampered cDC1 recruitment in adenocarcinoma was in turn related to lower transcript levels of cDC1-recruiting chemokines and an elevated β-catenin activation score and was associated with poor overall survival. Conclusions: Our data have identified an opportunity for the investigation of potentially novel therapeutic interventions in adenocarcinoma of the cervix, that is, β-catenin inhibition and cDC1 mobilization.
Expert consensus on the diagnosis and treatment of heat stroke in China
Authors: Shu-Yuan Liu, Jing-Chun Song, Han-Ding Mao, Jin-Bao Zhao, Qing Song
Journal: Military Medical Research (2020)

Abstract Heat stroke (HS) is a fatal disease caused by thermal damage in the body, and it has a very high mortality rate. In 2015, the People’s Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China, Expert consensus on standardized diagnosis and treatment for heat stroke . With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years, the 2015 consensus no longer meet the requirements for HS prevention and treatment. It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage, is more practical and is more in line with China’s national conditions. This new expert consensus includes new concept of HS, recommendations for laboratory tests and auxiliary examinations, new understanding of diagnosis and differential diagnosis, On-site emergency treatment and In-hospital treatment, translocation of HS patients and prevention of HS.
A novel simple biopsy-site identification tool
Authors: Rosanne Ottevanger, Marieke E. Weijns, Roel E. Genders
Journal: Journal of the American Academy of Dermatology (2020)

In patients with suspected skin cancer, preoperative biopsies are usually performed. It is important to confirm the histopathology and extent of the tumor before optimal treatment plans can be established. In case of ill-defined clinical borders, it is necessary to perform multiple biopsies for mapping the lesion. Especially when multiple biopsies are taken, it is important to carefully document the biopsy sites for identification afterward. This can be difficult, particularly because several weeks might pass before surgery is planned and the biopsy sites are fully healed and poorly visible if scarring is minimal. Photographic imaging is a helpful tool to identify biopsy sites. However, especially on the scalp it is hard to identify biopsy sites because of hairs covering them and the lack of distinct anatomic landmarks. Also, when multiple biopsies are taken it is sometimes challenging to reidentify every biopsy site. This can result in dislocation of the lesion, with possible positive surgical margins, unnecessary excision of healthy skin, and even surgery on the wrong site. Incorrect preoperative biopsy-site identification is found in up to 4.4% of Mohs micrographic surgery lesions.1McGinness J.L. Goldstein G. The value of preoperative biopsy-site photography for identifying cutaneous lesions.Dermatol Surg. 2010; 36: 194-197Crossref PubMed Scopus (43) Google Scholar Furthermore, 14% of malpractice claims among surgeons performing Mohs micrographic surgery are due to wrong-site operations.2Perlis C.S. Campbell R.M. Perlis R.H. et al.Incidence of and risk factors for medical malpractice lawsuits among Mohs surgeons.Dermatol Surg. 2006; 32: 79-83Crossref PubMed Google Scholar We present a simple solution for this clinical dilemma on hair-bearing scalp. An overview picture including anatomic landmarks with (multiple) markers of the biopsy sites before biopsies are taken can be a useful tool. In this way, detailed preoperative biopsy-site identification is performed and therefore prevents mistakes in identifying biopsy location (Fig 1). In this case, we used disposable cotton swab sticks and stickers.
PET/CT of Duodenal Gangliocytic Paraganglioma
Authors: David Morland, Sébastien Dejust, Mathilde Brasseur, Louise Monnier, Dimitri Papathanassiou
Journal: Clinical Nuclear Medicine (2020)

Abstract An 87-year-old woman with leg-type lymphoma underwent a staging 18 F-FDG PET/CT, which demonstrated besides leg lymphomatous lesions a round, well-defined, preduodenal mass with moderate FDG uptake. This mass remained unchanged after chemotherapy treatment completion, despite a complete metabolic response of lymphomatous lesions. A biopsy revealed a gangliocytic paraganglioma. Subsequent 18 F-FDOPA PET/CT and somatostatin receptor scintigraphy were positive and did not depict any other lesions.
Prevalence and recovery of adrenal insufficiency in steroid-dependent asthma patients receiving biologic therapy
Authors: Alexandra M. Nanzer, Aqib Chowdhury, Asma Raheem, Cris Roxas, Mariana Fernandes, Louise Thomson, Linda Green, Jaideep Dhariwal, Grainne D'Ancona, Brian D. Kent, Philip A. Kelly, David J. Jackson
Journal: European Respiratory Journal (2020)

<b>Adrenal insufficiency is common in previously steroid-dependent asthma patients. Morning serum cortisol is a valid and important first line test which can indicate adrenal insufficiency and can guide who might need dynamic testing.</b>http://bit.ly/2IVGNfI
Adenoma detection by Endocuff-assisted versus standard colonoscopy in routine practice: a cluster-randomised crossover trial
Authors: David Karsenti, Gaelle Tharsis, Bastien Perrot, Philippe Cattan, Gilles Tordjman, Franck Venezia, Elie Zrihen, Dominique Gillot, Agnes Gillet, Charles Hagege, Joelle Samama, Isabelle Etienney, Jean-Philippe Lab, Bernard Guigui, Jacqueline Zago, Bouchra Benkessou, Pascal Burtin, Maryan Cavicchi
Journal: Gut (2020)

Objective Endocuff Vision (ECV) is the second generation of a device designed to improve polyp detection. The aim of this study was to evaluate its impact on adenoma detection rate (ADR) in routine colonoscopy. Design This cluster-randomised crossover trial compared Endocuff-assisted (ECV+) with standard (ECV-) colonoscopy. Two teams of 11 endoscopists each with prior ECV experience, balanced in terms of basal ADR, gender and case volume were compared. In randomised fashion, the teams started with ECV+ or ECV- and switched group after inclusion of half of the cases. The main outcome criterion was ADR difference between ECV+ and ECV-. Subgroup analysis was done for physicians with low and high ADR (&lt; or ≥ 25%). Results During two periods of 20 and 21 weeks, respectively, the 22 endoscopists included 2058 patients (1032 ECV- vs 1026 ECV+, both groups being comparable). Overall ADR for both groups taken together was higher with ECV (39.2%) than without (29.4%; p&lt;0.001) irrespective of the sequence of use (ECV+ or ECV- first), but mostly in adenomas &lt;1 cm. In the physician subgroup analysis, only high detectors showed a significant ADR increase (from 31% to 41%, p&lt;0.001), while the increase in the low detectors was not significant (from 24% to 30%, p=0.11). ECV had a positive impact in all colonic locations, except for the rectum. No ECV- related complication was reported. Conclusion We observed a significant ADR difference of approximately 10% by the use of ECV. By subgroup analysis, this increase was significant only in physicians classified as high detectors. Trial registration number ClinicalTrials.gov ( NCT03344055 ).
Abstract P1-17-16: Deconstructing breast cancer reconstruction
Authors: Cecelia Allison, David Fear
Journal: Cancer Research (2020)

Abstract Background: The American Cancer Society currently invests more in breast cancer research than any other cancer type. However surgical treatments for breast cancer have been studied as far back as 3,000 BCE. Until the mid 19th century, the surgical treatment of breast cancer was limited either by sociocultural and religious views or technology. The advent of anesthesia and sterile practice in the late 1800s and early 1900s paved the way for innovation and precision. Synopsis: Despite being completely against breast reconstruction, Dr. William Halsted completely reconstructed breast cancer surgery. At the turn of the 20th century, Halsted’s new mastectomy procedure demonstrated to the world how technological advancements showed promise for a cure for breast cancer. The “Halsted Radical Mastectomy” recommended the removal of all diseased tissue including the pectoralis major muscle. Halsted later recommended further dissection of rectus abdominis, serratus anterior, subscapularis, latissimus dorsi and the teres major muscle without any breast reconstruction. With a local recurrence rate of 7% - an unheard of figure among the surgeons of the time- the “Halsted Radical Mastectomy” dominated the field for almost a century. With Halsted’s domination of technique came domination of thought. Halsted’s strong opinion against breast reconstruction influenced the American standard of care for breast cancer surgery for decades to follow. His treatment plan of mastectomy without reconstruction was the standard, so much so that other procedures for reconstruction, such as the latissimus dorsi pedicle flap (the first myocutaneous flap for breast reconstruction) were forgotten about for almost 70 years. Despite Halsted’s tight grasp on surgical thought, later 20th century innovations in breast reconstruction showed aesthetic results. Gradually, immediate breast reconstruction began to be advocated for all patients who were eligible. Breast cancer surgery and treatments continued to evolve and improve to ultimately lead to personalized medicine plans which have greatly improved patient outcomes. The shift in American surgical culture around breast reconstruction after mastectomies provide a lesson on how the power of cultural context shapes modern medical treatments. Significance: The medical recognition and treatment of breast cancer long outdated the modern day anesthetized, sterile, evidence-based procedures. Today, most women with early stage breast cancer will have some type of surgery. Therefore, it is important to appreciate the advancements and improvements in technology that have led us to the personalized medicine plans that have greatly improved outcomes. Citation Format: Cecelia Allison, David Fear. Deconstructing breast cancer reconstruction [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-16.