tbuckley/cabot-search huggingface dataset:
Abstract PS12-22: Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial
Authors: Valentina Guarneri, Saverio Cinieri, Maria Vittoria Dieci, Carmelo Bengala, Gabriella Mariani, Giancarlo Bisagni, Antonio Frassoldati, Claudio Zamagni, Laura Orlando, Carlo Alberto Giorgi, Gian Luca De Salvo, PierFranco Conte
Journal: Cancer Research (2021)

Abstract Background Despite endocrine therapy is the mainstay of treatment for HR+/HER2- metastatic breast cancer (MBC), patients with high disease burden or those at risk of visceral crisis are still offered first-line chemotherapy (CT). Chemotherapy is generally followed by maintenance hormonal therapy. The MAIN-A study is an investigator-driven, randomized phase III trial designed to compare maintenance everolimus (EVE) combined with aromatase inhibitors (AI) versus AI alone in pts with disease control after first-line CT.Methods Postmenopausal pts achieving disease control (stable disease, partial response or complete response) after first-line CT were randomly assigned to EVE 10 mg po daily plus AI or to AI alone. Primary aim was PFS in the ITT. We present here overall survival (OS) results and the impact of tumor characteristics on PFS.Results 110 pts were randomized to EVE+AI (n=52) or to AI (n= 58). Primary aim results have been already presented (Guarneri V, ESMO Breast 2019), showing a non-significant prolongation of median PFS in the ITT population for EVE+AI (9.9 mos vs 7.2 mos, HR 0.764, 95% CI 0.501-1.164. Patients with visceral metastases tended to experience shorter PFS as compared with patients with patients with bone/soft tissues metastases (median 11.1 mos vs 6.4 mos, p=0.0746). The levels of estrogen receptor expression (&amp;gt;or&amp;lt; 50%) did not impact PFS, overall and by treatment arm. At the time of this writing, a total of 61 death events have been recorded. No difference in OS was observed between the two arms (median 33.9 mos for EVE+AI vs 33.5 mos for AI, HR 0.97, 95% CI 0.59-1.61).Conclusions Maintenance EVE+AI did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first line chemotherapy. Citation Format: Valentina Guarneri, Saverio Cinieri, Maria Vittoria Dieci, Carmelo Bengala, Gabriella Mariani, Giancarlo Bisagni, Antonio Frassoldati, Claudio Zamagni, Laura Orlando, Carlo Alberto Giorgi, Gian Luca De Salvo, PierFranco Conte. Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-22.
Pregnant People’s Paradox—Excluded From Vaccine Trials Despite Having a Higher Risk of COVID-19 Complications
Authors: Rita Rubin
Journal: JAMA (2021)

Ai-ris Y. Collier, MD; Katherine McMahan, MS; Jingyou Yu, PhD; Lisa H. Tostanoski, PhD; Ricardo Aguayo, BS; Jessica Ansel, NP; Abishek Chandrashekar, MS; Shivani Patel, BA; Esther Apraku Bondzie, BA; Daniel Sellers, BS; Julia Barrett, BS; Owen Sanborn, BS; Huahua Wan, MS; Aiquan Chang, BA; Tochi Anioke, BS; Joseph Nkolola, PhD; Connor Bradshaw, BS; Catherine Jacob-Dolan, BS; Jared Feldman, BS; Makda Gebre, MSc; Erica N. Borducchi, PhD; Jinyan Liu, PhD; Aaron G. Schmidt, PhD; Todd Suscovich, PhD; Caitlyn Linde, PhD; Galit Alter, PhD; Michele R. Hacker, ScD; Dan H. Barouch, MD, PhD
Carbohydrates great and small, from dietary fiber to sialic acids: How glycans influence the gut microbiome and affect human health
Authors: Joanna K Coker, Oriane Moyne, Dmitry A. Rodionov, Karsten Zengler
Journal: Gut Microbes (2021)

Gut microbiome composition depends heavily upon diet and has strong ties to human health. Dietary carbohydrates shape the gut microbiome by providing a potent nutrient source for particular microbes. This review explores how dietary carbohydrates in general, including individual monosaccharides and complex polysaccharides, influence the gut microbiome with subsequent effects on host health and disease. In particular, the effects of sialic acids, a prominent and influential class of monosaccharides, are discussed. Complex plant carbohydrates, such as dietary fiber, generally promote microbial production of compounds beneficial to the host while preventing degradation of host carbohydrates from colonic mucus. In contrast, simple and easily digestible sugars such as glucose are often associated with adverse effects on health and the microbiome. The monosaccharide class of sialic acids exerts a powerful but nuanced effect on gut microbiota. Sialic acid consumption (in monosaccharide form, or as part of human milk oligosaccharides or certain animal-based foods) drives the growth of organisms with sialic acid metabolism capabilities. Minor chemical modifications of Neu5Ac, the most common form of sialic acid, can alter these effects. All aspects of carbohydrate composition are therefore relevant to consider when designing dietary therapeutic strategies to alter the gut microbiome.
Real world effectiveness of anti-IL-5/5R therapies is independent of co-eligibility for anti-IgE therapy
Authors: Andrew P. Hearn, Oliver D. Hug, Ziana A. Somani, Joanne Kavanagh, Grainne d'Ancona, Cris Roxas, Linda Green, Louise Thomson, Mariana Fernandes, Brian D. Kent, Jaideep Dhariwal, Alexandra M. Nanzer, David J. Jackson
Journal: European Respiratory Journal (2021)

<b>In a real-world setting, the clinical response to the anti-IL-5/5R mAbs mepolizumab and benralizumab in patients with severe eosinophilic asthma is independent of co-eligibility with the anti-IgE mAb omalizumab</b>https://bit.ly/2NfAitP
Delayed-onset myocarditis following COVID-19
Authors: Retesh Bajaj, Hannah C Sinclair, Kush Patel, Ben Low, Ana Pericao, Charlotte Manisty, Oliver Guttmann, Filip Zemrak, Owen Miller, Paula Longhi, Alastair Proudfoot, Boris Lams, Sangita Agarwal, Federica M Marelli-Berg, Simon Tiberi, Teresa Cutino-Moguel, Gerry Carr-White, Saidi A Mohiddin
Journal: The Lancet Respiratory Medicine (2021)
Abstract PD5-02: Dcis as a risk lesion for invasive breast cancer and death from other cancers
Authors: Alastair Thompson, Bridget Hilton, Joanna Dulson-Cox, Karen Clements
Journal: Cancer Research (2021)

Abstract Introduction: Ductal carcinoma in situ (DCIS) is considered a non-obligatory precursor of invasive breast cancer. Using a prospective cohort study of screen detected non-invasive neoplasia from a national breast screening program, this analysis examined subsequent DCIS or invasive cancers and death due to other cancers or other causes. Methods: Prospective data on 9191 screen detected non-invasive breast neoplasia with a median 9.2 years follow up was matched to a subsequent diagnosis of invasive breast cancer or death from another primary, non-breast cancer at any site or other cause of death, cross validating data from the National Cancer Registry, Hospital Episode Statistics and mortality data. Results: Following a diagnosis of screen detected DCIS, in 9191 women, for those undergoing breast conservation surgery (BCS), 413 women developed ipsilateral invasive breast cancer, at a proportion of 5/1000 per annum consistent over a decade and more. By contrast DCIS re-occurances in the same, conserved, breast (in 222 women) occurred at a similar rate for the first 5 years then the rate halved beyond 5 years. Contralateral breast cancer (DCIS or invasive) occurred in 431 women over the same time period. Mortality occurred in 1062/9191 (11.6%) women, attributed to breast cancer in 130/1062 (12.2%) and due to cancer at other sites in 397/1062 (37.4%). Death from other, non-breast, cancers was predominantly from primaries of the lung (98 women), ovary (43), pancreas (37) and colon (23) and rarely associated with a confounding diagnosis of invasive breast cancer (present in only 8% of those patients). Non-cancer mortality was identified in 496/1062 (46.7%) women, most commonly attributed to cardiovascular disease (in 188 women) or disease of the respiratory system (in 93). Conclusion: Screen detected DCIS is a marker for subsequent invasive breast cancer, but mortality from other, non-breast, cancers following treatment for DCIS is three times more likely than death due to breast cancer, suggesting DCIS is a more general marker for subsequent cancers than hitherto recognized. Awareness of, and potentially screening for, other cancers should be considered in women treated for DCIS. Citation Format: Alastair Thompson, Bridget Hilton, Joanna Dulson-Cox, Karen Clements, Sloane Project NHS Breast Screening Group. Dcis as a risk lesion for invasive breast cancer and death from other cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-02.
Abstract 10553: Left Atrial Wall Thickness in Patients With Hypertrophic Cardiomyopathy Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Hiroshi Hayashi, Meiso Hayashi, Yasushi Miyauchi, Kenta Takahashi, Ippei Tsuboi, Shunsuke Uetake, Hiroshige Murata, Kenji Yodogawa, Yu-ki Iwasaki, Wataru Shimizu
Journal: Circulation (2013)

Background: Several studies reported the effectiveness of catheter ablation for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM), but it remains unclear whether myocardia...
The outcomes of emergency hospital admissions with non-malignant upper gastrointestinal bleeding in England between 2003 and 2015
Authors: James Rees, Felicity Evison, Jemma Mytton, Prashant Patel, Nigel Trudgill
Journal: Endoscopy (2021)

Upper gastrointestinal bleeding (UGIB) is a common medical emergency with significant mortality. Despite developments in endoscopic and clinical management, only minor improvements in outcomes have been reported.This was a retrospective cohort study of patients with non-malignant UGIB emergency admissions in England between 2003 and 2015, using Hospital Episode Statistics. Multilevel logistic regression analysis examined the associations with mortality.242 796 patients with an UGIB admission were identified (58.8 % men; median age 70 [interquartile range (IQR) 53 - 81]). Between 2003 and 2015, falls occurred in both 30-day mortality (7.5 % to 7.0 %; P < 0.001) and age-standardized mortality (odds ratio (OR) 0.74, 95 % confidence interval [CI] 0.69 - 0.80; P < 0.001), including from variceal bleeding (OR 0.63, 95 %CI 0.45 - 0.87; P < 0.005). Increasing co-morbidity (Charlson score > 5, OR 2.94, 95 %CI 2.85 - 3.04; P < 0.001), older age (> 83 years, OR 6.50, 95 %CI 6.09 - 6.94; P < 0.001), variceal bleeding (OR 2.03, 95 %CI 1.89 - 2.18; P < 0.001), and a weekend admission (Sunday, OR 1.18, 95 %CI 1.12 - 1.23; P < 0.001) were associated with 30-day mortality. Of deaths at 30 days, 8.9 % were from ischemic heart disease (IHD) and the cardiovascular age-standardized mortality rate following UGIB was high (IHD deaths within 1 year, 1188.4 [95 %CI 1036.8 - 1353.8] per 100 000 men in 2003).Between 2003 and 2015, 30-day mortality among emergency admissions with non-malignant UGIB fell by 0.5 % to 7.0 %. Mortality was higher among UGIB admissions at the weekend, with important implications for service provision. Patients with UGIB had a much greater risk of subsequently dying from cardiovascular disease and addressing this risk is a key management step in UGIB.
Impact of circGSAP in Peripheral Blood Mononuclear Cells on Idiopathic Pulmonary Arterial Hypertension
Authors: Ping Yuan, Wen-Hui Wu, Su-Gang Gong, Rong Jiang, Qin-Hua Zhao, Bigyan Pudasaini, Yuan-Yuan Sun, Jin-Ling Li, Jin-Ming Liu, Lan Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Impact of circGSAP in Peripheral Blood Mononuclear Cells on Idiopathic Pulmonary Arterial Hypertension." American Journal of Respiratory and Critical Care Medicine, 203(12), pp. 1579–1583
England’s clinical negligence system needs urgent reform, say medical organisations
Authors: Clare Dyer
Journal: BMJ (2021)

The Academy of Medical Royal Colleges, the Hospital Consultants and Specialists Association, and the Medical Defence Union (MDU) are seeking urgent reform of the clinical negligence system in England, which has seen the estimated bill for outstanding claims rise to an “unsustainable” £84bn (€97.7bn; $118.4bn).

The organisations made the call in a joint letter to the prime minister, Boris Johnson, with a copy sent to the health and social care secretary for England, Matt Hancock. The MDU has long campaigned for reform of the current system, whose burgeoning cost represents “the …
The effects of 12 weeks of functional strength training on muscle strength, volume and activity upon exposure to elevated Gz forces in high-performance aircraft personnel
Authors: Monika Rausch, Frank Weber, Sven Kühn, Carla Ledderhos, Christoph Zinner, Billy Sperlich
Journal: Military Medical Research (2021)

Abstract Background Technological advancements in modern military and acrobatic jet planes have resulted in extraordinary psychophysiological loads being exerted upon flying personnel, including inducing neck and back pain. The purpose of this study was to examine the effects of 12 weeks of functional strength training on 1) the volume and strength of the neck and shoulder muscles and 2) muscular activity upon exposure to helmets of different masses and elevated G z forces in a long-arm centrifuge in high-performance aircraft personnel. Methods Eighteen participants underwent 12 weeks of functional strength training ( n = 12) or the control protocol ( n = 6) without additional strength training. Pre- and post-intervention tests included evaluations of isometric strength of the head extensor muscles, flexion, and lateral flexion and rotation, as well as magnetic resonance imaging (MRI) to measure the volume of the m. sternocleidomastoideus , m. trapezius , and deep neck muscles. Furthermore, during a long-arm centrifuge (+ 1.4 and + 3 G z ) protocol, the muscular activity levels of the m. sternocleidomastoideus , m. trapezius and m. erector spinae muscles were assessed without a flight helmet, with a helmet, and with a helmet and night vision goggles. Each participant’s perception of muscular strain was noted immediately after the long-arm centrifuge protocol. Results The maximal isometric strength in all exercises and muscle volumes increased in the training group but not the control group ( P &lt; 0.05). Relative muscle activity (%MVC) with a helmet decreased after the intervention in the training but not the control group ( P = 0.01). Relative muscle activity while wearing a helmet and night vision goggles was higher after intervention in the control group than in the training group ( P &lt; 0.01). The perceived muscular strain of the neck muscles induced by the long-arm centrifuge did not differ between the groups. Conclusion Twelve weeks of functional strength training improves the maximal isometric strength and volume of neck and shoulder muscles and leads to lower relative muscle activation upon exposure to elevated G z forces in a long-arm centrifuge.
Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation
Authors: Yuichiro Arima, Yoshiko Nakagawa, Toru Takeo, Toshifumi Ishida, Toshihiro Yamada, Shinjiro Hino, Mitsuyoshi Nakao, Sanshiro Hanada, Terumasa Umemoto, Toshio Suda, Tetsushi Sakuma, Takashi Yamamoto, Takehisa Watanabe, Katsuya Nagaoka, Yasuhito Tanaka, Yumiko K. Kawamura, Kazuo Tonami, Hiroki Kurihara, Yoshifumi Sato, Kazuya Yamagata, Taishi Nakamura, Satoshi Araki, Eiichiro Yamamoto, Yasuhiro Izumiya, Kenji Sakamoto, Koichi Kaikita, Kenichi Matsushita, Koichi Nishiyama, Naomi Nakagata, Kenichi Tsujita
Journal: Nature Metabolism (2021)
The emerging role of KDM5A in human cancer
Authors: Guan-Jun Yang, Ming-Hui Zhu, Xin-Jiang Lu, Yan-Jun Liu, Jian-Fei Lu, Chung-Hang Leung, Dik-Lung Ma, Jiong Chen
Journal: Journal of Hematology & Oncology (2021)

Abstract Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.
Abstract SP066: Omitting radiotherapy in select situations
Authors: R Jagsi
Journal: Cancer Research (2021)

Abstract Advances in breast imaging, surgery, pathology, and systemic therapy have rendered certain patients with breast cancer at sufficiently low risk of local recurrence that they may reasonably consider the omission of radiation therapy to reduce toxicity and burden. For decades, clinical trials have been conducted to try to identify the population of patients in whom the risk of recurrence in the absence of radiotherapy is sufficiently small that omission of radiotherapy might reasonably be considered after breast conserving surgery. Although trials to date, including ER+ patients selected based upon clinicopathologic characteristics alone, have largely proven unsuccessful, guidelines do currently identify older women with early-stage, node-negative, hormone receptor-positive disease to be candidates for radiotherapy omission after lumpectomy. This talk will review historical trials evaluating the role of radiotherapy after breast conserving surgery as well as exciting ongoing trials leveraging our growing appreciation of tumor biology to identify a population of patients who may reasonably consider omitting radiotherapy after breast conserving surgery. Citation Format: R Jagsi. Omitting radiotherapy in select situations [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP066.
Economic Analysis of Mobile Integrated Health Care Delivered by Emergency Medical Services Paramedic Teams
Authors: Feng Xie, Jiajun Yan, Gina Agarwal, Richard Ferron
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Mobile integrated health care (MIH) is a new model of community-based health care to provide on-site urgent or nonurgent care. Niagara emergency medical services (NEMS) started MIH in 2018 to serve the Niagara region of Ontario, Canada. However, its economic impact is unknown. <h3>Objective</h3> To compare time on task and cost between MIH and ambulance delivered by NEMS from a public payer's perspective. <h3>Design, Setting, and Participants</h3> This economic evaluation was an analysis of the NEMS databases regarding responses to emergency calls by the NEMS from 2016 to 2019. Emergency calls serviced by MIH in 2018 to 2019 were used as an intervention cohort. Propensity score matching was used to identify a 1:1 matched cohort of calls serviced by regular ambulance response for the same period and 2 years prior. Statistical analyses were performed from January to April 2020. <h3>Exposures</h3> MIH compared with matched ambulance services. <h3>Main Outcomes and Measures</h3> The main outcomes were the time on task (including time on scene and time at hospital) and costs. Costs were calculated in 2019 Canadian dollars using cost per minute and compared with the 3 ambulance cohorts. <h3>Results</h3> In 2018 to 2019, there were 1740 calls serviced by MIH for which a matched ambulance cohort was identified for the same period and 2 years prior. The mean (SD) time on task was 72.7 (51.0) minutes for MIH, compared with 84.1 (52.0) minutes, 84.3 (54.1) minutes, and 79.4 (42.0) minutes for matched ambulance in 2018 to 2019, 2017 to 2018, and 2016 to 2017, respectively. Of calls serviced by MIH, 498 (28.6%) required ED transport (ie, after MIH team assessment, transport to ED was deemed to be necessary or demanded by the patient), compared with 1300 (74.7%) calls serviced by ambulance in 2018 to 2019, 1294 (74.4%) in 2017 to 2018, and 1359 (78.1%) in 2016 to 2017. The mean (SD) total cost per 1000 calls was $122 760 ($78 635) for MIH compared with $294 336 ($97 245), $299 797 ($104 456), and $297 269 ($81 144) for regular ambulance responses in the 3 matched cohorts, respectively. <h3>Conclusions and Relevance</h3> Compared with regular ambulance response, MIH was associated with a substantial reduction in the proportion of patients transported to the ED, leading to a substantial saving in total costs. This finding suggests that the MIH model is a promising and viable solution to meeting urgent health care needs in the community, while substantially improving the use of scarce health care resources.
Risk of Venous Thromboembolism in Hospitalized COVID-19 Patients Undergoing Thromboprophylaxis: Meta-analysis of Cohort Studies
Authors: A. Jamil, U. Jamil, S. Dahal, V. Gunnam, H. Najafi, S. M. Montazerin, F. Shojaei, F. Kahe, J. Marszalek, J. Lee, G. Chi
Journal: Circulation (2020)
Prognostic Value of Coronary CT Angiography in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Klaus F. Kofoed, Thomas Engstrøm, Per E. Sigvardsen, Jesper J. Linde, Christian Torp-Pedersen, Martina de Knegt, Peter R. Hansen, Thomas Fritz-Hansen, Jan Bech, Merete Heitmann, Olav W. Nielsen, Dan Høfsten, Jørgen T. Kühl, Ilan E. Raymond, Ole P. Kristiansen, Ida H. Svendsen, M.H. Domínguez Vall-Lamora, Charlotte Kragelund, Jens D. Hove, Tem Jørgensen, Gitte G. Fornitz, Rolf Steffensen, Birgit Jurlander, Jawdat Abdulla, Stig Lyngbæk, Hanne Elming, Susette K. Therkelsen, Erik Jørgensen, Lene Kløvgaard, Lia E. Bang, Steffen Helqvist, Søren Galatius, Frants Pedersen, Ulrik Abildgaard, Peter Clemmensen, Kari Saunamäki, Lene Holmvang, Gunnar Gislason, Henning Kelbæk, Lars V. Køber
Journal: Journal of the American College of Cardiology (2021)
Abstract 11028: Riser Pulse Rate Pattern Was Strongly Associated With Cardiac Damage and Cardiovascular Events:The Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Hisaya Kobayashi, Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2019)

Introduction: The riser pattern, an abnormal blood pressure(BP) rhythm in which sleep BP exceeds awake BP, is associated with cardiovascular events. However, the association among the riser pattern...