tbuckley/cabot-search huggingface dataset:
Abstract 12082: Pulmonary Arterial Hypertension: Rapid Sequential Combination Therapy With PDE5 Inhibitors and Endothelin Receptor Antagonists Substantially Improves Hemodynamics at Early Follow-up
Authors: Tilmann T Kramer, Daniel Dumitrescu, Felix Gerhardt, Phillip Nattmann, Christopher Hohmann, Stephan Baldus, Stephan Rosenkranz
Journal: Circulation (2019)

Introduction: Evidence suggests that upfront combination therapy with ERA and PDE5i in patients with newly diagnosed PAH is associated with a reduction in morbidity and mortality events. No data ar...
159P Obesity and oral contraceptives reduce the preventive benefit of breastfeeding against breast cancer in Mexican women
Authors: H.F. Rodriguez Gutierrez, A. Guerra Cepeda, R. Cerda Flores, O. Solis Coronado, D. Reding Hernandez, J.F. Gonzalez Guerrero, O. Vidal Gutierrez, D.C. Perez Ibave, M.D.L. Garza Rodriguez
Journal: Annals of Oncology (2021)
High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group
Authors: Najla El Jurdi, Heba Elhusseini, Joan Beckman, Todd E. DeFor, Grigori Okoev, John Rogosheske, Aleksandr Lazaryan, Kristen Weiler, Veronika Bachanova, Brian C. Betts, Bruce R. Blazar, Claudio G. Brunstein, Fiona He, Shernan G. Holtan, Murali Janakiram, Radhika Gangaraju, Joseph Maakaron, Margaret L. MacMillan, Armin Rashidi, Erica D. Warlick, Smita Bhatia, Gregory Vercellotti, Daniel J. Weisdorf, Mukta Arora
Journal: Blood Cancer Journal (2021)

Abstract Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with systemic inflammation and endothelial dysfunction, increasing risk for thromboembolic events (TEE). In 145 adult recipients who developed cGVHD after a matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 32(22%) developed at least 1 TEE event, and 14(10%) developed 2 TEE events. The 5-year cumulative incidence of TEE was 22% (95% CI, 15–29%) with a median time from cGVHD to TEE of 234 days (range, 12–2050). Median time to the development of LE DVT or PE was 107 (range, 12–1925) compared to 450 days (range, 158–1300) for UE DVT. Cumulative incidence of TEE was 9% (95% CI, 0–20%), 17% (95% CI, 9–25%), and 38% (95% CI, 22–55%) in those with mild, moderate, and severe GVHD, respectively. Higher risk for TEE was associated with cGVHD severity (hazard ratio [HR] 4.9, [95% CI, 1.1–22.0]; p = 0.03), non-O-donor to recipient ABO match compared to O-donor to O-recipient match (HR 2.7, [95% CI, 1.0–7.5]; p = 0.053), and personal history of coronary artery disease (HR 2.4, [95% CI, 1.1–5.3]; p = 0.03). TEE was not associated with 2-year non-relapse mortality or 5-year overall survival.
Abstract 15163: Differences in Preferences Between Physicians and Patients for the Use and Dosing of Direct Oral Anticoagulants for Atrial Fibrillation
Authors: Jennifer A Rymer, Debbe McCall, Mellanie T Hills, Tracy Y Wang
Journal: Circulation (2020)

Introduction: Direct oral anticoagulants (DOACs) are effective in reducing the risk of stroke for patients with atrial fibrillation (AF) only if prescribed at the labeled dose. Little is known about patient or clinician preferences for DOAC selection and dosing. Methods: We consented 240 physicians treating ≥20 patients with AF and 343 patients with AF. Physician knowledge of DOAC dosing was tested with 4 hypothetical patient case scenarios. Both patients and physicians were asked to grade the importance of 25 factors in anticoagulation decision-making. Results: Among physicians, the median age was 55 years, 13% were female, 23% were primary care providers. Most physicians (63%) stated empirically they would never/rarely use an adjusted lower dose if the patient did not meet dose adjustment criteria. However, in hypothetical case scenarios of a patient indicated for full dose DOAC, 40.8% of clinicians under-dosed apixaban (&lt;5 mg bid daily) and 17.1% for rivaroxaban (&lt;20 mg daily). In scenarios where a patient met dosing criteria for reduced dose DOAC, 64.6% (apixaban 2.5 mg bid daily) and 71.7% (rivaroxaban 15 mg daily) of physicians chose the reduced dose DOAC answer. Only 32.1% of clinicians answered all 4 scenarios correctly. Among patients with AF, the median age was 65 years, 74% were female, 85% had AF &gt;1 year and 89% were currently anticoagulated. Patients and physicians both ranked stroke prevention and avoiding severe bleeding very important when choosing a DOAC. Physicians were more likely than patients to rank cost as very important, patients were more likely than physicians to consider the following very important: may cause minor bleeding, the dose of med can be reduced if need to, reversal agent available, and how long the drug has been on market ( Figure ). Conclusions: DOAC dosing strategies may be driven by gaps in physician knowledge, on top of varying treatment beliefs and preferences between physicians and patients.
사례보고 : 만성 C형간염 환자에서 Peginterferon α-2b와 Ribavirin 병합치료 중 발생한 돌발성 난청 1예
Authors: 신민기, 김태효, 주강, Chang Yoon Ha, Hyun Ju Min, Jung，Woon-Tae, Ok-Jae Lee
Journal: Clinical and Molecular Hepatology (2009)

돌발성 난청은 페그인터페론 치료 시에 발생하는 드문 부작용으로 알려져 있다. 저자 등은 60세 만성 C형간염 환자에서 페그인터페론알파와 리바비린 병합치료 중 42주째에 우측 귀에 돌발성 난청이 발생하여, 페그인터페론 치료를 중단하고 스테로이드 투여 후 완전히 회복된 사례를 경험하였다. 페그인터페론 치료 시 청력에 대한 세심한 관찰이 필요하며, 청력소실 발생 시 치료의 지속 여부에 대해서는 발생 시점, 환자의 치료 의지, 청력소실의 정도 등에 따라 임상의가 주의 깊게 판단해야 할 것으로 생각한다.
Abstract 17414: Combination Therapy of Sildenafil and Rapamycin Alleviates Doxorubicin Induced Cardiotoxicity With Improvement of Skeletal Muscle Function
Authors: Arun Samidurai, Donatas Kraskauskas, Lei XI, Rakesh C Kukreja, Anindita Das
Journal: Circulation (2020)

Background: Doxorubicin (DOX) is a chemotherapeutic agent for multiple cancers, however, it causes systemic inflammation with multi-organ injury, including irreversible skeletal muscle (SM) dysfunction and cardiotoxicity. Treatment either with phosphodiesterase 5 inhibitor, sildenafil (SILD) or mammalian target of rapamycin (mTOR) inhibitor, Rapamycin (RAPA) protects against myocardial infarction (MI), heart failure and also has anti-tumor effects. We contemplated that unique combination of SILD and RAPA may enhance protective effect against DOX-induced SM dysfunction and cardiotoxicity with attenuation of inflammation. Methods and Results: Adult female C57 mice were treated with DOX (5 mg/kg/week; i.p.) with/without RAPA (0.25 mg/kg/d, i.p.) and/or SILD (1.4 mg/kg/day; in drinking water) for 4 weeks. Cardiac function (ejection fraction) and SM grip strength were significantly decreased in DOX-treated mice ( Fig. A, B ), which were improved by co-treatment with SILD+RAPA. Myostatin which inhibits myogenesis, was significantly upregulated upon DOX treatment, but was reduced by SILD+RAPA in SM ( Fig. C) . Adult mouse cardiomyocytes were treated with 1 μM DOX with/without 100 nM RAPA and/or 10 μM SILD for 24 hours. SILD+RAPA reduced DOX-induced apoptosis (assessed by TUNEL assay, Fig. D ) and ROS-generation (assessed by H2DCFDA, Fig. E ) while maintaining mitochondrial membrane potential (Δψ m ; measured by JC-1 staining, Fig. F ). Immunofluorescence staining revealed enhanced aggregation of ASC (adaptor molecule of inflammasome) following DOX treatment, which was inhibited by SILD+RAPA in cardiomyoblast (H9C2; Fig. G) and SM sol 8 cells ( Fig. H). Conclusion: Combination therapy with SILD+RAPA protects against DOX-induced cardiac and SM injury. Dual strategy of mTOR-PDE5 inhibition may be a novel approach to alleviate DOX toxicity during cancer treatment.
Market Exclusivity and Changes in Competition and Prices Associated With the US Food and Drug Administration Unapproved Drug Initiative
Authors: Simon J. Gunter, Aaron S. Kesselheim, Benjamin N. Rome
Journal: JAMA Internal Medicine (2021)

In 2006, the US Food and Drug Administration (FDA) launched the Unapproved Drug Initiative (UDI) to document supporting data for several thousand drugs that had remained on the US market continually since before the agency began reviewing safety and effectiveness in 1938. 1 As an incentive, the FDA offered market exclusivity to the first manufacturer to receive approval of a legacy drug.In the short term, these market exclusivity periods drove up drug prices, most notably for the antigout drug colchicine. 2,3 In November 2020, the FDA announced that the UDI program was ending, citing concerns that the program raised prices without generating new clinical data for most drugs. 4 To assess the long-term effects of the UDI, we evaluated market exclusivity characteristics under the UDI program and how competition and prices changed 5 years after drug approval.
Covid-19: NHS to trial rapid diagnostics and Saturday clinics to tackle elective care backlog
Authors: Gareth Iacobucci
Journal: BMJ (2021)

In electrically driven left atria isolated from guinea pig and rat, a new milrinone analog, 6-ethyl-5-propionyl-1,2-dihydro-2-oxo-3-pyridine carbonitrile, produced a positive inotropic effect that was not dependent on adrenergic mechanisms and was more marked than that exerted by the parent compound. Its inotropic action was almost completely abolished by pretreatment of atria with adenosine deaminase and correlated well with its binding ability to the cardiac adenosine A<sub>1</sub> receptor. In this regard, the analog showed a 100-fold higher affinity for adenosine receptor than that of milrinone. Moreover, it shifted to the right the concentration-response curves for the negative inotropic action of the stable adenosine receptor agonist R-phenylisopropyladenosine. The new analog behaved as a competitive inhibitor of Type III phosphodiesterase isolated from both guinea pig and rat, although its <i>K</i><sub>i</sub> value was 10 times higher than that of milrinone. However, an increase in cAMP levels does not seem to be involved in the mechanism of action of the new compound, because the presence of carbachol did not decrease the extent of the positive inotropic effect of the analog and did not modify its EC<sub>50</sub> in either guinea pig or rat myocardial preparations. Taken together, these results suggest that the milrinone structure can be modified, giving rise to a more active compound whose inotropic effect in both guinea pig and rat appears to be more clearly related to antagonism toward endogenous adenosine than to Type III phosphodiesterase inhibition.
Postponed Withholding: Balanced Decision-Making at the Margins of Viability
Authors: Janicke Syltern, Lars Ursin, Berge Solberg, Ragnhild Støen
Journal: The American Journal of Bioethics (2021)

Advances in neonatology have led to improved survival for periviable infants. Immaturity still carries a high risk of short- and long-term harms, and uncertainty turns provision of life support into an ethical dilemma. Shared decision-making with parents has gained ground. However, the need to start immediate life support and the ensuing difficulty of withdrawing treatment stands in tension with the possibility of a fair decision-making process. Both the parental “instinct of saving” and “withdrawal resistance” involved can preclude shared decision-making. To help health care personnel and empower parents, we propose a novel approach labeled “postponed withholding.” In the absence of a prenatal advance directive, life support is started at birth, followed by planned redirection to palliative care after one week, unless parents, after a thorough counseling process, actively ask for continued life support. Despite the emotional challenges, this approach can facilitate ethically balanced decision-making processes in the gray zone.
Abstract 17426: Acute Myocardial Infarction Due to Right Coronary Artery Occlusion Following Blunt Thoracic Trauma
Authors: Kimberly O'Dell, Jacob Mok, Saad Sikanderkhel
Journal: Circulation (2020)

Blunt thoracic wall trauma can rarely lead to acute coronary artery injury and occlusion , and mostly involves the left anterior descending artery due to its vulnerable anterior anatomic positioning. Herein, we present a case of a young man who presented as a ST segment elevation MI (STEMI) with right coronary artery (RCA) occlusion after a blunt thoracic wall trauma. Clinical Vignette: A 37-year-old man with no previous medical history was brought to our ER with blunt chest wall trauma following a motor vehicle collision. Initial workup showed multiple fractures, a right pneumothorax and a pelvic hematoma. EKG performed for chest pain showed STEMI in the inferior and lateral leads. A 2D echocardiogram then showed inferolateral wall hypokinesis. Serial troponin I levels trended up sharply from 0.4 initially. After initiating intravenous heparin and cangrelor, the patient underwent emergent coronary angiography which revealed a rare, RCA occlusion with a thrombus. The patient then successfully underwent aspiration thrombectomy with restoration of TIMI grade III blood flow. Discussion: Hence, we presented a rare case of RCA occlusion resulting from blunt thoracic wall trauma. While musculoskeletal pain may mask the symptoms of myocardial hypoperfusion, a high index of suspicion for coronary artery thrombosis can lead to desirable outcomes in such patients.
Abstract 16570: Systemic Inflammation Alters the Bleeding-Ischemic Balance in High-Bleeding Risk Patients Undergoing Percutaneous Coronary Interventions
Authors: Johny Nicolas, Davide Cao, Bimmer E Claessen, Mauro Chiarito, Samantha Sartori, Hanbo Qiu, Matteo Nardin, Anton Camaj, Anastasios Roumeliotis, Zhongjie Zhang, Ridhima Goel, Rishi Chandiramani, Usman Baber, Joseph Sweeny, Prakash Krishnan, Annapoorna Kini, Samin K Sharma, George Dangas, Roxana Mehran
Journal: Circulation (2020)

Introduction: Prognosis in high-bleeding risk (HBR) patients after percutaneous coronary intervention (PCI) is largely dependent on risk of ischemic/bleeding events. Inflammation is known to increase the ischemic risk following PCI in the general population, yet its impact on HBR patients remains unknown. Hypothesis: We assessed the hypothesis that inflammation, as reflected by elevated high-sensitivity C - reactive protein (hsCRP), increases the risk of ischemic and bleeding events in HBR patients undergoing PCI. Methods: We included patients who underwent PCI at a tertiary care center between 2014 and 2017. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the Academic Research Consortium (ARC)-HBR consensus. Patients were then stratified into high (≥3 mg/l) and low (&lt;3 mg/ml) baseline hsCRP level; those presenting with myocardial infarction (MI) or hsCRP &gt;10 mg/l were excluded. The main outcomes of interest were major adverse cardiac events (MACE) (composite of all-cause death, MI, and target vessel revascularization) and bleeding events. Results: Out of 7,186 patients included, 3,403 (42.3%) fulfilled the ARC-HBR definition of whom 1,046 (34.4%) had high hsCRP. These patients were frequently female, younger, and had more cardiovascular risk factors (diabetes, kidney disease, and peripheral artery disease) yet similar angiographic features (multivessel disease, syntax score, and lesion length) than those with low hsCRP. Although risk of MACE at 1 year was similar in HBR patients with either high or low hsCRP, mortality risk was significantly higher in the former group ( Figure 1 ). In addition, HBR patients with high hsCRP were more likely to have periprocedural bleeding (OR 1.72, 95% CI [1.14-2.58], p=0.01) but similar risk of 1-year major bleeding as HBR patients with low hsCRP ( Figure 1 ). Conclusion: In conclusion, inflammation is associated with periprocedural bleeding and 1-year mortality in HBR patients undergoing PCI.
133P Breast cancer in young women (BCYW): Different entity or different needs?
Authors: J.C. Sánchez, B. Nunez Garcia, M. Mendez Garcia, M. Blanco Clemente, A.M. Morito Aguilar, B. De La Puente Orteu, C. De la Fuente, D. Suárez, M. Provencio Pulla, B. Cantos Sanchez De Ibarguen
Journal: Annals of Oncology (2021)
シクロオキシゲナーゼと心血管系【JST・京大機械翻訳】
Authors: A Mitchell Jane, S Kirkby Nicholas, Ahmetaj-Shala Blerina, C Armstrong Paul, Crescente Marilena, Ferreira Plinio, Lopes Pires Maria Elisa, Vaja Ricky, D Warner Timothy
Journal: Pharmacology & Therapeutics (2021)
Association of Socioeconomic Disadvantage With Long-term Mortality After Myocardial Infarction
Authors: Adam N. Berman, David W. Biery, Curtis Ginder, Avinainder Singh, Jonggyu Baek, Rishi K. Wadhera, Wanda Y. Wu, Sanjay Divakaran, Ersilia M. DeFilippis, Jon Hainer, Christopher P. Cannon, Jorge Plutzky, Donna M. Polk, Khurram Nasir, Marcelo F. Di Carli, Arlene S. Ash, Deepak L. Bhatt, Ron Blankstein
Journal: JAMA Cardiology (2021)

Socioeconomic disadvantage is associated with poor health outcomes. However, whether socioeconomic factors are associated with post-myocardial infarction (MI) outcomes in younger patient populations is unknown.To evaluate the association of neighborhood-level socioeconomic disadvantage with long-term outcomes among patients who experienced an MI at a young age.This cohort study analyzed patients in the Mass General Brigham YOUNG-MI Registry (at Brigham and Women's Hospital and Massachusetts General Hospital in Boston, Massachusetts) who experienced an MI at or before 50 years of age between January 1, 2000, and April 30, 2016. Each patient's home address was mapped to the Area Deprivation Index (ADI) to capture higher rates of socioeconomic disadvantage. The median follow-up duration was 11.3 years. The dates of analysis were May 1, 2020, to June 30, 2020.Patients were assigned an ADI ranking according to their home address and then stratified into 3 groups (least disadvantaged group, middle group, and most disadvantaged group).The outcomes of interest were all-cause and cardiovascular mortality. Cause of death was adjudicated from national registries and electronic medical records. Cox proportional hazards regression modeling was used to evaluate the association of ADI with all-cause and cardiovascular mortality.The cohort consisted of 2097 patients, of whom 2002 (95.5%) with an ADI ranking were included (median [interquartile range] age, 45 [42-48] years; 1607 male individuals [80.3%]). Patients in the most disadvantaged neighborhoods were more likely to be Black or Hispanic, have public insurance or no insurance, and have higher rates of traditional cardiovascular risk factors such as hypertension and diabetes. Among the 1964 patients who survived to hospital discharge, 74 (13.6%) in the most disadvantaged group compared with 88 (12.6%) in the middle group and 41 (5.7%) in the least disadvantaged group died. Even after adjusting for a comprehensive set of clinical covariates, higher neighborhood disadvantage was associated with a 32% higher all-cause mortality (hazard ratio, 1.32; 95% CI, 1.10-1.60; P = .004) and a 57% higher cardiovascular mortality (hazard ratio, 1.57; 95% CI, 1.17-2.10; P = .003).This study found that, among patients who experienced an MI at or before age 50 years, socioeconomic disadvantage was associated with higher all-cause and cardiovascular mortality even after adjusting for clinical comorbidities. These findings suggest that neighborhood and socioeconomic factors have an important role in long-term post-MI survival.
Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin
Authors: Mathias Mahn, Inbar Saraf-Sinik, Pritish Patil, Mauro Pulin, Eyal Bitton, Nikolaos Karalis, Felicitas Bruentgens, Shaked Palgi, Asaf Gat, Julien Dine, Jonas Wietek, Ido Davidi, Rivka Levy, Anna Litvin, Fangmin Zhou, Kathrin Sauter, Peter Soba, Dietmar Schmitz, Andreas Lüthi, Benjamin R. Rost, J. Simon Wiegert, Ofer Yizhar
Journal: Neuron (2021)
Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine
Authors: Ofer Beharier, Romina Plitman Mayo, Tal Raz, Kira Nahum Sacks, Letizia Schreiber, Yael Suissa-Cohen, Rony Chen, Rachel Gomez-Tolub, Eran Hadar, Rinat Gabbay-Benziv, Yuval Jaffe Moshkovich, Tal Biron-Shental, Gil Shechter-Maor, Sivan Farladansky-Gershnabel, Hen Yitzhak Sela, Hedi Benyamini-Raischer, Nitzan D. Sela, Debra Goldman-Wohl, Ziv Shulman, Ariel Many, Haim Barr, Simcha Yagel, Michal Neeman, Michal Kovo
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. The significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.
PCPS,IABP,ステロイドパルスにて救命しえた劇症型心筋炎の一症例
Authors: Yonemitsu Yuichi, Kaihatsu Kenji, Nonaka Yasuyuki, Haraguchi Eiko, Kaneko Akihiro, Yamana Shota, Kudo Yorihiro, Ban Chikanori, Kawasaki Satoru, Takei Asumi, Sumiya Makoto, Onishi Yoshio, Udaka Isao
Journal: Circulation (2008)
Nigel Standfield: vascular surgeon who trained generations worldwide
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Nigel Standfield was born in Wuppertal, Germany, to John Standfield, who had served in the British and Indian armies during the second world war and then in British intelligence, and Mollie (nee Taylor), a sports teacher who had trained in the army. The family moved to Street, Somerset, where John became an advertising manager, but he was also an amateur botanist. Fortunately, Standfield inherited both his mother’s passion for sports and teaching and his father’s aptitude for science. At Sexey’s School, in Bruton, Somerset, he was popular with his fellow students and teachers alike and as an all-rounder he excelled at cricket and football, as well as academically. He was very much a west country man, solidly focused on home and family life.

Soon after starting out as a medical student at King’s College Hospital Medical School in London he lost both his parents but continued with his studies, more determined than ever to succeed in his ambition to become a surgeon. He met his future wife, Donna, a sister at the same hospital, at an anaesthetists’ party. Standfield invited her to a cricket match the following week, and their immediate spark was to last their long marriage. They had three sons.

In 1990 Standfield was appointed consultant vascular surgeon at Hammersmith Hospital and Royal Postgraduate Medical School and the Royal Brompton Hospital, London. He was elected a council member of the Royal College of Surgeons of England in 2016.

Standfield had a varied clinical vascular practice with a particular interest in congenital vascular malformations, which was the focus of his inaugural professorial lecture “From Tolpuddle …