tbuckley/cabot-search huggingface dataset:
Abstract P2-15-11: A phase II trial of genexol-PM and doxorubicin in patients with advanced Her-2 negative breast cancer
Authors: Eun Kyung Cho, Hyo Yeon Yun, Yun Yeong Kim, Yong Soon Jeon, Heungkyu Park
Journal: Cancer Research (2020)

Abstract Background: Genexol PM is a lyophilized polymeric micellar formulation of paclitaxel that delivers a higher paclitaxel dose with lower vehicle-related toxicities than conventional paclitaxel formulations. This study was designed to evaluate the efficacy and safety of genexol- PM and doxorubicin combination in advanced Her-2 negative Breast cancer as first line treatment. Methods: Patients with advanced Her-2 negative Breast cancer received Genexol-PM at 260mg/m2 on day 1 and doxorubicin 50mg/m2 on day 1 of 3-week interval cycle. Six to nine cycles of combination chemotherapy were planned unless there was disease progression. The primary endpoint was objective response rate. Results: Thirty patients received this combination chemotherapy with a median 6cycles per patient (range 1-9). The objective response rate was 67% with disease control rate 87%, Median duration of response was 5.5months (95%CI 3.0-8.1months). Median progression free survival was 7.4 months (95%CI 5.3-9.6months) and overall survival 38.7months (95%CI 21.4-55.9months). The common toxicities were alopecia(93%), peripheral neuropathy(60%), nausea(57%), neutropenia(47%). The most common G3/4 toxicities were neutropenia(43%) and neutropenic fever(27%). There was no treatment related mortality. Conclusion: Genexol-PM, CrEL-free paclitaxel, in combination with doxorubicin demonstrated favorable antitumor activity in advanced Her-2 negative breast cancer. The most common G3/4 toxicities was neutropenia but it was manageable. Citation Format: Eun Kyung Cho, Hyo Yeon Yun, Yun Yeong Kim, Yong Soon Jeon, Heungkyu Park. A phase II trial of genexol-PM and doxorubicin in patients with advanced Her-2 negative 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 P2-15-11.
Potential Effects of Coronaviruses on the Cardiovascular System
Authors: Mohammad Madjid, Payam Safavi-Naeini, Scott D. Solomon, Orly Vardeny
Journal: JAMA Cardiology (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.
Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial
Authors: Heiko Schöder, Mei-Yin C. Polley, Michael V. Knopp, Nathan Hall, Lale Kostakoglu, Jun Zhang, Howard R. Higley, Gary Kelloff, Heshan Liu, Andrew D. Zelenetz, Bruce D. Cheson, Nina Wagner-Johnston, Brad S. Kahl, Jonathan W. Friedberg, Eric D. Hsi, John P. Leonard, Lawrence H. Schwartz, Wyndham H. Wilson, Nancy L. Bartlett
Journal: Blood (2020)
Managing Stable Ischemic Heart Disease
Authors: Elliott M. Antman, Eugene Braunwald
Journal: New England Journal of Medicine (2020)

The preferred contemporary approach to the management of stable ischemic heart disease, also referred to as chronic coronary syndrome,1 is not well defined. Two strategies are commonly used.2 The conservative strategy uses guideline-based medical therapy, including antianginal drugs as well as disease-modifying agents, such as hypolipidemic, antithrombotic, and renin–angiotensin blocking therapies. The invasive strategy adds coronary angiography, followed by either percutaneous coronary intervention or coronary-artery bypass grafting, to guideline-based medical therapy. Important advances have occurred in both strategies, leading to equipoise as to which approach is preferable for patients with stable ischemic heart disease.3,4 The International Study of Comparative Health . . .
Optimizing the Trade-off Between Learning and Doing in a Pandemic
Authors: Derek C. Angus
Journal: JAMA (2020)

Optimizing the Trade-off Between Learning and Doing in a PandemicThe world is united regarding the goal of ending the coronavirus disease 2019 (COVID-19) pandemic but not the strategy to achieve that goal.One stark example is the debate over whether to prescribe available therapies, such as quinine-based antimalarial drugs (eg, chloroquine or hydroxychloroquine), or test these drugs in randomized clinical trials (RCTs).At the heart of the problem is one of the oldest dilemmas in human organizations: the "exploitation-exploration" trade-off. 1Exploitation refers to acting on current knowledge, habits, or beliefs despite uncertainty.This is the "just do it" option: give various therapies (eg, chloroquine) to affected patients based on current knowledge or a hunch.Exploration refers to actions taken to generate new knowledge and reduce uncertainty, eg, testing therapies in an RCT.This is the "must learn" option.Currently, these approaches are framed as a choice: do something (treat the patient) or learn something (test the drug).This dilemma is now playing out across the world, with many clinicians recommending treatments (eg, antiviral agents or immunomodulating drugs), even while researchers and regulators emphasize that evidence is limited and the need for RCTs is paramount.The problem is that exploitation/ exploration trade-offs are almost always best solved by a strategy that blends both: simultaneously learning while doing.The joint goal of this integrated effort is to maximize short-term outcomes (eg, the best possible recovery of patients who must be treated now) and long-term outcomes (eg, the fastest path to discovery and dissemination of new treatments).This balance is elusive, and potentially impossible without an integrated approach-a single system that "learns while doing," with alacrity.However, medicine is organized to do each task separately: clinical practice (doing) and clinical research (learning) are addressed by separate institutions, procedures, and funding.Hospitals and physician groups practice medicine while academic institutions, entities like the National Institutes of Health, and pharmaceutical companies focus on scientific discovery.There are many reasons for this division of labor, not the least of which was the Belmont Report, which codified that research should be kept separate from the practice of medicine, or patients' interests will be usurped. 2There are, however, huge costs to this division, including delays in knowledge acquisition and dissemination.In normal times, these costs are somewhat suppressed or ignored, but in a crisis such as the COVID-19 pandemic, they come into sharp focus.Thus, as pressure mounts to "just do something," the challenge to learn simultaneously and efficiently becomes increasingly difficult, placing both individuals and society in peril.
Abstract 8966: C1q/TNF-Related Proteins (CTRPs), a Family of Novel Adipokines, Induce Vascular Relaxation through the Adiponectin Receptor-1/AMPK/eNOS/Nitric Oxide Signaling Pathway
Authors: Qijung Zheng, Yuexing Yuan, Hui Su, Wei Yi, Wayne Bond Lau, Yajing Wang, Xiaoliang Wang, Yang Sun, Bernard Lopez, Theodore Christopher, Jonathan M Peterson, Jonathan M Peterson, G William Wong, Shiqiang Yu, Dinghua Yi, Xin-Liang Ma
Journal: Circulation (2011)

Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction and vascular injury. However, APN knockout animals manifest only modest systemic dysfunction unless metabolically challenged. The CTRP (C1q/TNF-related proteins) family has recently been identified as APN paralogs. Some CTRP members share APN’s metabolic regulatory function. However, the vascular biology of CTRPs remains completely unknown. This study assessed the vasoactivity of currently identified murine CTRP members utilizing in vitro and in vivo experimental models, and elucidated underlying molecular mechanisms in HUVECs. Of eight CTRPs investigated, three CTRPs (3, 5, and 9) caused significant vasorelaxation in concentration-dependent fashion, while the remaining CTRPs neither constricted nor dilated aortic segments. The vasodilatory potency of CTRP9 exceeded that of APN (3-fold), is endothelium-dependent, and mediated by nitric oxide (NO). Plasma CTRP9 levels were markedly increased in APN knockout mice, and significantly reduced in high-fat-diet induced obesity/diabetic mice (P&lt;0.05). One week of in vivo CTRP9 administration initiated after 3 weeks high-fat-diet, at a dose restoring physiological CTRP9 levels, significantly improved vascular endothelial function (P&lt;0.01). Mechanistically, CTRP9 increased AMPK/Akt/eNOS phosphorylation and increased endothelial NO production. AMPK knockdown completely blocked CTRP9-induced Akt/eNOS phosphorylation and NO production. Akt knockdown had no significant effect upon CTRP9-induced AMPK phosphorylation, but blocked eNOS phosphorylation and NO production. Adiponectin receptor 1 (AdipoR1), but not receptor 2 (AdipoR2), knockdown blocked CTRP9-induced AMPK/Akt/eNOS phosphorylation and NO production. Finally, pre-incubating vascular rings with an AMPK-inhibitor abolished CTRP9-induced vasodilatory effects. Collectively, we have provided the first evidence that CTRP9 is a novel vasodilatory/vasculoprotective adipokine, potentially compensatory for APN’s vascular effects in APN knockout animals. Moreover, we have demonstrated that CTRP9 exerts its vascular biological effects via the AdipoR1/AMPK/eNOS dependent/NO mediated signaling pathway.
Abstract P6-08-32: Genetic variation and the role of multi-gene testing for hereditary breast cancer: A single institution experience
Authors: Kit Yu Lu, Meagan Smith, Julia Verbiar, Haleigh Minor, Jennifer Lapse, Latesha Blair, Lisa Torp
Journal: Cancer Research (2020)

Abstract Introduction: The introduction of multi-gene testing for hereditary forms of breast cancer has changed the clinical approach to genetic testing for breast cancer patients. Recent consensus guideline now recommends genetic testing for all patients with a personal history of breast cancer and updated testing to those who have had negative germline BRCA 1 and 2 testing. This is a single institutional experience regarding the use and outcomes of multi-gene testing and updated testing. Methods: This is a retrospective analysis of germline multi-gene testing for breast cancer patients at our institution. Information on tumor histology, personal and family history of cancer, age at diagnosis, and genetic testing information was obtained through records review. Results: Between January 1, 2015 and December 31, 2018, 1568 breast cancer patients were diagnosed or treated at our institution. Of those, 26% of the patients had genetic results (age range 23-87; median age 52; &amp;lt;1% Male; 88% non-Hispanic whites, 8% blacks, 2% Asians, 2% Hispanics). Eight percent of the patients were found to carry a pathogenic variant that the NCCN guidelines designated as sufficient evidence to have an increased risk for breast cancer. Of those, only 3.4% were BRCA 1 and 2 mutations. The prevalent pathogenic variants found in multi-gene testing were BRCA 1/ 2 (3.4%), CHEK2 (2.2%), PALB2 (1%), TP53 (1%), PMS2 (1%), MYTYH (0.74%), FANCC (0.25%), ATM (0.25%), MSH2 (0.25%), MSH6 (0.25%), NBN (0.25%), and RAD51C (0.25%). Fifteen patients had initial testing looking only for the presence of germline BRCA 1 and 2 mutations. Of those, updated expanded testing identified an additional two patients who carried a pathogenic variant that was previously unidentified. Conclusion: Multi-gene testing and expanded panel testing of all breast cancer patients could increase the detection of pathogenic variants and may have a potential clinical impact for patients and their family. Further understanding of genetic patterns and variation in multi-gene testing is needed. Increasing public awareness and decreasing the cost of genetic testing are also important to improve the rates of multi-gene testing. Citation Format: Kit Yu Lu, Meagan Smith, Julia Verbiar, Haleigh Minor, Jennifer Lapse, Latesha Blair, Lisa Torp. Genetic variation and the role of multi-gene testing for hereditary breast cancer: A single institution experience [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 P6-08-32.
Abstract P4-17-05: Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database
Authors: Eungyeong Lee, Heein Jo, Jai Hong Han, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Myong Cheol Lim, Young-Joo Won, Eun Sook Lee, Eun Sook Lee
Journal: Cancer Research (2020)

Abstract Background: Male breast cancer (MBC) is a very rare disease. There are ambiguous opinions about treatment outcomes and survival outcome. This study aimed to investigate the incidence and survival outcome of male breast cancer in Korea. Additionally, we evaluated the differences between male and female breast cancer (FBC). Method: We identified 226,612 breast cancer cases diagnosed between 1999 and 2016 in the Korea Central Cancer Registry (KCCR). We retrospectively analyzed the data that patient demographics and clinical information between MBC and FBC. Overall survival (OS) was estimated according to sex, age, histologic type, stage. Results: Of the 226,612 patients, 1,052 had male breast cancer patient and 225,560 had female breast cancer patients. The ratio of male to female was 0.0047. MBC patients were diagnosed the most frequently in those aged 60-69 years. In contrast, FBC was diagnosed the most frequently in those aged 40-49 years (p&amp;lt;.0001). Male patient received less adjuvant therapy than female patients (radiotherapy, MBC vs. FBC = 8% vs. 22%, chemotherapy, 41.9% vs. 55.7%, p&amp;lt;.0001). The 5-years OS rates after the diagnosis of breast cancer were 88.8% for all patients. MBC has a lower 5-years OS rate than FBC (76.2% for men, and 88.9% for women, p&amp;lt;.0001). Both groups showed lower survival in patients aged ≥60 years. The 5-years OS rates of invasive type were 75.8% for men and 89% for women. The OS rate was lower in both groups as the stage increased. Conclusion: We found that there is a difference between MBC and FBC. The survival outcomes in MBC were worse than that of FBC. This study showed the different OS patterns according to the age, histology, and stage. Based on these results, clinicians need to recognize the difference from FBC when treating MBC. Citation Format: Eungyeong Lee, Heein Jo, Jai Hong Han, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Myong Cheol Lim, Young-Joo Won, Eun Sook Lee, Eun Sook Lee. Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database [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 P4-17-05.
Abstract P4-13-05: The oncological safety of autologous fat grafting after breast conserving surgery for breast cancer: A systematic review, meta- analysis and meta regression analysis of observational studies
Authors: Salim Tayeh, Amtul R Carmichael, Humaa Darr, Zuhair Al-Fardan, Abdul Kasem, Moustapha Hamdi, Kefah Mokbel
Journal: Cancer Research (2020)

Abstract Background: Autologous fat grafting (AFG) has been widely adopted to correct deformities resulting from breast conserving surgery (BCS) for breast cancer. However, clinical and animal studies and in vitro experiments have revealed conflicting results regarding the oncological safety of AFG. Aim: The aim of this study was to systematically evaluate the current literature regarding the oncological safety of AFG in patients who underwent BCS for breast cancer by performing a meta-analysis of observational studies. Methods: A literature research was performed using the PubMed and Embase search engines from conception until May 2019 to identify all studies of patients who underwent AFG following BCS for breast cancer. Reference lists of retrieved articles and relevant previous reviews were also searched. The primary outcome was the locoregional recurrence rate. For case-control studies a standard meta-analysis was performed to calculate a pooled relative risk (RR). For case series studies, subgroup analysis and meta-regression techniques were used with historical control data to increase reliability. Results: 26 studies reporting on 1640 BCS patients who had undergone AFG met the inclusion criteria for analysis. There were 11 case-control studies and 15 case series. For the case-controlled studies, meta-analysis using the random effects model revealed no significant difference in the locoregional recurrence rates between the AFG and control groups [RR=0.82(95% CI= 0.41-1.66)]. The mean follow up duration from surgery for the AFG group and the control group was 39 and 49 months, respectively. For the case series and historical controls, the locoregional recurrence rates were 1.85% and 2.53% respectively (p=0.33) according to subgroup and meta regression analysis. There was no strong evidence of publication bias however selection bias could not be excluded. Conclusions: Our study suggests that AFG does not increase the risk of locoregional recurrence after BCS for breast cancer. However further prospective research is needed to confirm the oncological safety of this technique particularly in patients with high risk disease. Citation Format: Salim Tayeh, Amtul R Carmichael, Humaa Darr, Zuhair Al-Fardan, Abdul Kasem, Moustapha Hamdi, Kefah Mokbel. The oncological safety of autologous fat grafting after breast conserving surgery for breast cancer: A systematic review, meta- analysis and meta regression analysis of observational studies [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 P4-13-05.
Abstract 154: Guideline Removal of Atropine and Survival After Adult In-Hospital Cardiac Arrest With Non-Shockable Rhythms
Authors: Mathias J Holmberg, Ari Moskowitz, Sebastian Wiberg, Lise Witten, Anne V Grossestreuer, Tuyen Yankama, Sarah Perman, Michael W Donnino, Lars W Andersen
Journal: Circulation (2018)

Introduction: Atropine was removed from the 2010 American Heart Association’s Advanced Cardiac Life Support guidelines as routine management of non-shockable cardiac arrest, although the evidence to support or refute the use of atropine is lacking. In a previous study, atropine usage was shown to subsequently decline markedly. Whether removing atropine from the guidelines has affected survival remains unknown. Methods: Using the Get With The Guidelines®-Resuscitation registry, we included adult patients with an index in-hospital cardiac arrest between 2006-2015. Non-shockable and shockable cardiac arrest patients with high vs. low propensity score to receive atropine were separated into two cohorts. An interrupted time-series analysis was used to compare survival before (pre-exposure) and after (post-exposure) introduction of the 2010 guidelines. A difference-in-difference approach was used to compare the interrupted time-series results between the non-shockable and shockable cohorts to account for guideline changes unrelated to atropine. Results: We included 21,822 non-shockable and 4,268 shockable cardiac arrests. Patient characteristics were similar between the pre-exposure and post-exposure period. Atropine was used for 9,170 (86%) non-shockable and 733 (34%) shockable cardiac arrests in the pre-exposure period and 3,903 (35%) non-shockable and 339 (16%) shockable cardiac arrests in the post-exposure period. The change over time in survival from the pre-exposure to the post-exposure period was not significantly different for the non-shockable compared to the shockable cohort (mean difference: 2.0% [95%CI: -0.7, 4.6] per year, p = 0.15, Figure). The immediate change in survival after introducing the guidelines was also not different between the cohorts (mean difference: 3.9% [95%CI: -2.2, 10], p = 0.21, Figure). Conclusions: The removal of atropine from the 2010 guidelines was not associated with a change in survival in our analysis.
Covid-19: Trump declares intention to “re-open economy” within weeks against experts’ advice
Authors: Owen Dyer
Journal: BMJ (2020)

The weights of 1105 children who needed the extraction of deciduous teeth under general anaesthesia were significantly lighter than the weights of 527 children who did not have dental extractions. Dietary analysis was made for 204 children after extraction and 131 children of the non-extraction group. Children who require multiple extractions before the age of 6 may be suffering an undetected malnutrition.
Targeting pulmonary capillary permeability to reduce lung congestion in heart failure: a randomized, controlled pilot trial
Authors: Glenn M. Stewart, Bruce D. Johnson, Dennis L. Sprecher, Yogesh N.V. Reddy, Masaru Obokata, Steven Goldsmith, Brad Bart, Anna Oughton, Christina Fillmore, David J. Behm, Barry A. Borlaug
Journal: European Journal of Heart Failure (2020)
Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts
Authors: V. Dunnett-Kane, E. Burkitt-Wright, F.H. Blackhall, A. Malliri, D.G. Evans, C.R. Lindsay
Journal: Annals of Oncology (2020)

Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer while also being implicated in a diverse group of developmental disorders named the 'RASopathies', including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFC), and capillary malformation-arteriovenous syndrome (CM-AVM). It remains unclear why (i) there is little overlap in mutational subtype between Ras-driven malignancies associated with sporadic disease and those associated with the RASopathy syndromes, and (ii) RASopathy-associated cancers are usually of different histological origin to those seen with sporadic mutations of the same genes. For instance, germline variants in KRAS and NRAS are rarely found at codons 12, 13 or 61, the most common sites for somatic mutations in sporadic cancers. An exception is CS, where germline variants in codons 12 and 13 of HRAS occur relatively frequently. Given recent renewed drug interest following early clinical success of RAS G12C and farnesyl transferase inhibitors, an improved understanding of this relationship could help guide targeted therapies for both sporadic and germline cancers associated with the Ras pathway.