tbuckley/cabot-search huggingface dataset:
Evaluation of Fall and Fracture Risk Among Men With Prostate Cancer Treated With Androgen Receptor Inhibitors
Authors: Zin W. Myint, Harry D. Momo, Danielle E. Otto, Donglin Yan, Peng Wang, Jill M. Kolesar
Journal: JAMA Network Open (2020)

Importance A high incidence of fall and fracture in a subset of patients treated with androgen receptor inhibitors (ARIs) has been reported, although the relative risk (RR) of fall and fracture for patients who receive ARI treatment is unknown. Objective To evaluate whether treatment with ARIs is associated with an elevated relative risk for fall and fracture in patients with prostate cancer. Data Sources Cochrane, Scopus, and MedlinePlus databases were searched from inception through August 2019. Study Selection Randomized clinical trials comparing patients with prostate cancer treated with any ARI or placebo were included. Data Extraction and Synthesis Two independent reviewers used a standardized data extraction and quality assessment form. A mixed effects model was used to estimate the effects of ARI on relative risk, with included studies treated as random effects and study groups treated as fixed effects in the pooled analysis. Sample size for each study was used to weight the mixed model. Statistical analysis was performed from August to October 2019. Main Outcomes and Measures The primary outcome was RR of fall and fractures for patients receiving ARI treatment. Results Eleven studies met this study’s inclusion criteria. The total population was 11 382 men (median [range] age: 72 [43-97] years), with 6536 in the ARI group and 4846 in the control group. Participants in the ARI group could have received enzalutamide, apalutamide, or darolutamide in combination with androgen deprivation therapy or other enzalutamide combinations; patients in the control group could have received placebo, bicalutamide, or abiraterone. The reported incidence of fall was 525 falls (8%) in the ARI group and 221 falls (5%) in the control group. The incidence of fracture was 242 fractures (4%) in the ARI group and 107 fractures (2%) in the control group. Use of an ARI was associated with an increased risk of falls and fractures: all-grade falls (RR, 1.8; 95% CI, 1.42-2.24; P &amp;amp;lt; .001); grade 3 or greater fall (RR, 1.6; 95% CI, 1.27-2.08; P &amp;amp;lt; .001); all-grade fracture (RR, 1.59; 95% CI, 1.35-1.89; P &amp;amp;lt; .001), and likely grade 3 or greater fracture (RR, 1.71; 95% CI, 1.12-2.63; P = .01). Conclusions and Relevance Use of ARI was associated with an increase in falls and fractures in patients with prostate cancer as assessed by a retrospective systematic review and meta-analysis. Further studies are warranted to identify and understand potential mechanisms and develop strategies to decrease falls and fractures associated with ARI use.
Abstract 13726: Remote Cardiac Rehabilitation is a Good Alternative of Outpatient Cardiac Rehabilitation in the Covid-19 Era
Authors: Atsuko Nakayama, Naoko Takayama, Hiroyuki Morita, Issei Komuro
Journal: Circulation (2020)

Introduction: As the COVID-19 pandemic has rapidly spread throughout the world, people need to take social distance to protect from SARS-CoV-2 infection. In such a stressful situation, physical activity is obliged to be reduced, and the risk of cardiovascular events was elevated in patients with heart failure (HF). The remote cardiac rehabilitation (CR) might be an alternative of outpatient-CR program. Methods: We prospectively investigated patients hospitalized for HF with left ventricular ejection fraction &lt; 50% from January 2019 to April 2020. For patients who participated in the remote-CR program, telephone support by a nurse specialized in HF and cardiologists was provided every two weeks for five months after discharge. Emergency readmission rate within 30 days after discharge was compared among outpatient-CR, remote-CR and non-CR groups, and EQ-5D score as an indicator for quality of life (QOL) was compared between outpatient-CR and remote-CR groups. Results: The participation rate of our remote-CR program for HF patients, which had been launched in 2019, was elevated during COVID-19 pandemic. As was observed in the outpatient-CR group (n=70), emergency readmission rate within 30 days after discharge was lower in remote-CR group (n=31) as compared with non-CR group (n=137) (p=0.02). EQ-5D score 30 days after discharge was higher in remote-CR group than outpatient-CR group (p=0.03). Conclusions: Remote-CR is as effective as outpatient-CR for the improvement in short-term prognosis after discharge in patients hospitalized for heart failure, suggesting that remote-CR program can be provided as a good alternative of outpatient-CR program.
Neoadjuvant Therapy for Melanoma: A U.S. Food and Drug Administration—Melanoma Research Alliance Public Workshop
Authors: Kristen L. Mueller, Marc R. Theoret, Steven J. Lemery, Laleh Amiri-Kordestani, Charlotte E. Ariyan, Michael B. Atkins, Donald A. Berry, Christian U. Blank, Angela M. DeMichele, Patrick M. Forde, Nageatte Ibrahim, Patricia Keegan, Tara C. Mitchell, Rebecca A. Moss, Caroline Robert, Rajeshwari Sridhara, Janis M. Taube, Michael T. Tetzlaff, Jennifer A. Wargo, Keith T. Flaherty, Michael J. Kaplan, Suzanne L. Topalian, Ashley F. Ward, Marc S. Hurlbert
Journal: Clinical Cancer Research (2020)

Tremendous progress has been made in treating patients with metastatic melanoma over the past decade. In that timeframe, the FDA has approved 12 novel treatments for patients with advanced unresectable melanoma, comprising both kinase-targeted therapies and immune checkpoint inhibitors (ICI), and five treatments for adjuvant (postoperative) use in patients with high-risk resectable stage III melanoma. It is not known whether outcomes can be further improved by administering kinase inhibitors or ICI in the neoadjuvant (presurgical) setting in patients with high-risk resectable melanomas. Noting research community interest in exploring the neoadjuvant approach for treating melanoma and recognizing that early harmonization of methodologies may expedite the development of therapeutics in this space, the FDA and Melanoma Research Alliance convened a public workshop on November 6, 2019, in National Harbor, Maryland, to discuss key issues. The workshop consisted of 23 faculty and included more than 250 live participants. Topics discussed included opportunities for advancing novel endpoints for regulatory purposes as well as translational research, clinical trial design considerations, and strategies for optimizing patient selection while mitigating risk.
Abstract 15803: Effectiveness of Direct Oral Anticoagulant versus Warfarin in the Treatment of Left Ventricular Thrombus
Authors: Nicholas Isom, Zafar Ali, Tarun Dalia, Farhad Sami, Uzair Mahmood, Tyler Buechler, Amandeep Goyal, Zubair Shah, Kamal gupta
Journal: Circulation (2020)

Introduction: Left ventricular thrombus (LVT) is associated with a higher risk of ischemic stroke and peripheral embolization. Societal guidelines recommend the use of warfarin, with direct oral anticoagulants (DOACs) only for patients unable to tolerate warfarin. Data on natural history and thrombus resolution with anticoagulation (AC), especially with DOACs is scarce. We studied the natural history of LVT with AC with emphasis on comparing warfarin and DOACs use. Methods: This is a single center, retrospective study conducted in an academic medical center. We identified patients (echocardiogram, CT or MRI) with a confirmed LVT study who were followed at our center. Chart review was conducted to collect clinical information at presentation and on follow up. Type and duration of anticoagulation, INR levels and clinical outcomes (bleeding, ischemic stroke or peripheral embolization, mortality) were recorded. Thrombus resolution on follow up imaging was also recorded. Results: LVT was confirmed in a total of 110 patients. Mean age was 59±14 years. 79% were men. Underlying etiology was chronic ischemic cardiomyopathy in 58%, non-ischemic cardiomyopathy in 23%. AC was started in 96 (87%) patients (in remaining patients AC was thought to be contraindicated). Of those on long-term AC, 60 patients (63%) were treated with warfarin, 3 patients (3%) with enoxaparin and 32 patients (33%) with a DOACs. At one year follow up, 11 patients (10%) had a stroke while on any AC. Two of these patients had hemorrhagic stroke (both on warfarin) and 9 patients had ischemic stroke. Of those with ischemic stroke 7 were on warfarin and 2 patients on DOACs had ischemic strokes. Of those with ischemic stroke on warfarin, 71% had subtherapeutic INR. The 1-year risk of any stroke was 15% in warfarin group (12% risk of ischemic stroke) compared to 6% in the DOACs group (p= 0.33). Total of 55 (57%) of patient started on AC had resolution of thrombus. 37 (63%) patients on warfarin and 18 (53%) on DOACs had resolution of thrombus (p= 0.85). Conclusions: One year risk of stroke with LVT is high (10%) even with AC. Most patients with ischemic stroke on warfarin had subtherapeutic INR. There was no statistical difference in stroke risk or rate of thrombus resolution between warfarin and DOACs treated patients.
Abstract 15495: Interleukin 18 Binding Protein Predicts Future Cardiovascular Morbidity and Mortality in Subjects Undergoing Coronary Angiography - the Casablanca Cohort
Authors: Joost H Rutten, Inge C van den Munckhof, Craig Magaret, Rhonda F Rhyne, Leo A Joosten, Mihai G Netea, Niels P Riksen, James L Januzzi, Roland van Kimmenade
Journal: Circulation (2020)

Introduction: Increased systemic inflammation is one of the key triggers in the initiation and progression of atherosclerosis. We investigated interleukin 18 binding protein (IL-18BP), a new inflammatory marker of the IL-1 cytokine family, on its predictive value for cardiovascular disease in subjects under investigation for stenotic atherosclerotic disease. Methods: We performed a prospective, single-center, investigator-initiated, observational cohort study in 927 subjects who underwent coronary and/or peripheral angiography. The cohort was randomly split into a discovery (n=627) and a validation set (n =267). Predictive value for incident cardiovascular events (composite of cardiovascular death, myocardial infarction and stroke), cardiovascular mortality and all-cause mortality was investigated using Cox proportional hazard models, including concordance index analyses and assessment of net reclassification for 10-year cardiovascular risk categories using Weibull modelling. Results: An one standard deviation increase in log-transformed IL-18BP was strongly associated with cardiovascular events (HR 1.96, 95% CI 1.54-2.51), cardiovascular mortality (HR 1.59, 95% CI 1.04-2.44) and all-cause mortality (HR 1.72, 95 CI 1.43-2.07), independent of the traditional cardiovascular risk factors, including body mass index. C-index of a clinical model for prediction of cardiovascular events improved from 0.69 (95% CI to 0.62-0.75) to 0.73 (95% CI 0.67-0.79) with inclusion of IL-18BP in the model; in doing so, a reclassification of 35.9% (p &lt; 0.001) for events was demonstrated. Conclusions: Among a population of patient undergoing coronary angiography, results of IL18-BP measurement improved cardiovascular risk prediction beyond the traditional risk factors. Kaplan-Meier survival curves for CV events during one-year follow up comparing tertiles IL-18BP (discovery set)
The BMJ Awards 2020: showcase of this year’s winning teams
Authors: Matt Limb
Journal: BMJ (2020)

The BMJ Awards, held virtually on 7 October 2020, have once again highlighted the best teamwork the NHS has to offer across a wide area of medical and healthcare practice.This year the judges praised the way winning projects had harnessed the energy and enthusiasm of staff and patients to craft better services, deploying novel and inspirational approaches.Here we highlight the winners, and we recommend readers to find out more from the teams themselves in showcase videos at https://thebmjawards.bmj.com/showcase. Anaesthesia and perioperative medicine team of the year
Senescence Reprogramming by TIMP1 Deficiency Promotes Prostate Cancer Metastasis
Authors: Ilaria Guccini, Ajinkya Revandkar, Mariantonietta D'Ambrosio, Manuel Colucci, Emiliano Pasquini, Simone Mosole, Martina Troiani, Daniela Brina, Raheleh Sheibani-Tezerji, Angela Rita Elia, Andrea Rinaldi, Nicolò Pernigoni, Jan Hendrik Rüschoff, Susanne Dettwiler, Angelo M. De Marzo, Emmanuel S. Antonarakis, Costanza Borrelli, Andreas E. Moor, Ramon Garcia-Escudero, Abdullah Alajati, Giuseppe Attanasio, Marco Losa, Holger Moch, Peter Wild, Gerda Egger, Andrea Alimonti
Journal: Cancer Cell (2020)
Human innate lymphoid cell precursors express CD48 that modulates ILC differentiation through 2B4 signaling
Authors: Dejene M. Tufa, Ashley M. Yingst, George Devon Trahan, Tyler Shank, Dallas Jones, Seonhui Shim, Jessica Lake, Kevin Winkler, Laura Cobb, Renee Woods, Kenneth Jones, Michael R. Verneris
Journal: Science Immunology (2020)

Human common ILC progenitors acquire CD48 and CD52, defining innate lymphoid cell precursors and NK progenitors.
Abstract 148: A Machine Learning-based Dispatch Rule for Drone-delivered Defibrillators
Authors: Jamal Chu, K.H. Benjamin Leung, Sheldon Cheskes, Paul Snobelen, Gordon Nevils, Ian Drennan, Timothy Chan
Journal: Circulation (2020)

Introduction: Drone-delivered defibrillators may reduce response time for out-of-hospital cardiac arrest (OHCA). However, an optimal dispatch rule is not yet known. Methods: We identified all suspected OHCAs in Peel Region, Ontario, Canada from Jan. 2014 to Dec. 2019. We trained a neural network model to predict emergency medical services (EMS) response times using OHCA location, distance from responding ambulance, day of week and time of day. Instead of least-squares loss, our model optimized a loss function that penalized weighted errors in the dispatch decision (type I/II error). Assuming drones were deployed from three bases in the region, we calculated drone response time to each suspected OHCA using real drone specifications. Our dispatch rule dispatched a drone when its calculated response time was shorter than the predicted EMS response time. Response time was calculated as the minimum of the drone and EMS response times. The performance of our dispatch rule was compared on out-of-sample OHCAs using 5-fold cross validation to the baseline cases of (1) no drones, and (2) drone dispatch to every suspected OHCA. Statistical analysis on the median response times was performed using a right-tailed sign test. Results: We identified 4774 suspected OHCAs with a median historical EMS response time of 6.0 minutes. Using our dispatch rule, median response time was significantly shorter at 3.9 minutes (P&lt;0.001). Drones were dispatched to 3803 cases (79.7%) and of those, drone response was faster than EMS in 3076 cases (80.9%). When the drone was not dispatched, it would have been slower than EMS in 856 cases (88.1%). Sending a drone to every suspected OHCA resulted in an identical median response time of 3.9 minutes (P&lt;0.001), with drones arriving before EMS in 3191 cases (66.8%). Conclusion: A machine learning-based dispatch rule can achieve similar response times as a policy that dispatches a drone to all suspected OHCAs, while dispatching drones less frequently.
Abstract 17113: Secondary Infections Are Common in Patients Hospitalized for COVID-19 and Are Associated With Severe Outcomes
Authors: Elizabeth R Anderson, Tariq Azam, Husam Shadid, Michael Pan, Hanna Berlin, Chelsea Meloche, Rafey Feroze, Jeff Leya, Patrick O'Hayer, Rayan Kaakati, abbas bitar, Kishan Padalia, Daniel Perry, Pennelope Blakely, Peiyao Zhao, Lili Zhao, Salim Hayek
Journal: Circulation (2020)

Background: Secondary infections occur in 10-15% of critically ill sepsis patients. Anecdotal reports suggest secondary infections are common in coronavirus disease 2019 (COVID-19), however data are lacking. We examine the rate of secondary infections in hospitalized patients with COVID-19 and its impact on the cytokine surge and in-hospital outcomes. Methods: The Michigan Medicine Covid-19 Cohort (M2C2) is an ongoing prospective observational study in which detailed clinical, laboratory and outcome data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without respiratory symptoms were not included in this cohort. We define secondary infections as physician-diagnosed and treated bacterial or viral infections secondary to SARS-CoV-2. Results: Of 553 COVID-19 patients hospitalized at Michigan Medicine, 191 (34.5%) developed a secondary infection during hospitalization. The mean age of patients with a secondary infection was 60 years, 61.3% were male compared to 58.8 years, 53.5% male in patients with no secondary infection. Bacterial pneumonia, including ventilator-associated pneumonia, was the most prevalent secondary infection among hospitalized patients (78.5%). Other secondary infections included urosepsis (14.1%), bacteremia (16.8%), and 17.3% of patients developed other types of infections such as shingles and clostridium difficile. 25.8% of patients without secondary infections received antibiotics during their admission compared to 47.1% of patients with secondary infections. Multiple secondary infections (&gt;1) occurred in 43 (8.2%) of patients. Patients with secondary infections were more likely to develop acute kidney injury (78.0% vs. 38.3%, p&lt;0.0001), acute respiratory distress syndrome (78.0% vs. 22.3%, p&lt;0.0001), and death (26.2% vs. 10.2%, p&lt;0.0001) during their hospitalization compared to patients without secondary infections. Conclusions: Secondary infections are common in hospitalized patients with COVID-19 and are associated with life-threatening complications and high mortality. This study suggests that secondary infection prevention may be especially important in COVID-19 patients.
Abstract 13029: Endothelial Hspa12b and Yap Cooperatively Promote Angiogenesis Following Myocardial Infarction
Authors: Min Fan, Kun Yang, Yana Wang, Fei Tu, Tuanzhu Ha, Li Liu, John Kalbfleisch, David L Williams, Chuanfu Li
Journal: Circulation (2019)

Introduction: HSPA12B is predominantly expressed in endothelial cells and plays an important role in angiogenesis. YAP is an important effector in Hippo signaling and plays a critical role in cell ...
Abstract 12824: Relationship Between Baseline TRS2P Score and LDL-C Alone or in Combination in Predicting the Absolute Benefits of More Versus Less Intensive Statin Therapy in an ASCVD: Analysis From the TNT Trial
Authors: Toshiyuki Nishikido, Rana Fayyad, Shari A Melamed, Kausik K Ray
Journal: Circulation (2019)

Introduction: Guidelines recommend intensive statin therapy for those with ASCVD but implementation is poor. Understanding the determinants of absolute benefit may help improve guideline implementa...
Abstract 234: Validation of a Termination-of-resuscitation Rule for Patients with Refractory Out-of-hospital Cardiac Arrest at an Emergency Department in Japan
Authors: Akira Funada, Yoshikazu Goto, Masayuki Takamura
Journal: Circulation (2020)

Introduction: In Japan, emergency medical service (EMS) providers are prohibited from cardiopulmonary resuscitation (CPR) termination in the field and must transport all out-of-hospital cardiac arrest (OHCA) patients to a hospital, regardless of the return of spontaneous circulation (ROSC). We previously developed a termination of resuscitation (TOR) rule for emergency department physicians (ED-TOR) treating OHCA patients using data from the All-Japan Utstein Registry between 2005 and 2009, when CPR was performed according to the 2005 guidelines. The ED-TOR rule recommends CPR termination when patients in the emergency department meet all of the following criteria: initial unshockable rhythm, arrest unwitnessed by bystanders and no prehospital ROSC. Hypothesis: We aimed to validate the ED-TOR rule using more recent data, where CPR was performed according to the 2010 and 2015 guidelines, comparing the relevance of the ED-TOR rule with the universal basic life support TOR (BLS-TOR) rule, which consists of the following criteria: no prehospital ROSC, unwitnessed arrest by EMS providers and no shock received. Methods: We analysed 552,554 OHCA patients (age ≥ 18 years) treated by EMS providers. OHCA patients witnessed by EMS providers were excluded. Data were obtained from a prospectively recorded All-Japan Utstein Registry from 2013 to 2017. The study endpoints were specificity and a positive predictive value (PPV) for predicting 1-month mortality after OHCA with the ED-TOR and BLS-TOR rules. Results: The overall 1-month survival rate was 4.3% (23,733/552,554). The proportions of OHCA patients who fulfilled the ED-TOR and BLS-TOR criteria were 59.6% and 83.8%, respectively. The specificity and PPV of the ED-TOR and BLS-TOR rules for predicting 1-month mortality were 93.2% (95% confidence interval [CI], 92.8%-93.5%) and 99.5% (95% CI, 99.5%-99.5%) and 82.6% (95% CI, 82.1%-83.1%) and 99.1% (95% CI, 99.1%-99.1%), respectively. Conclusions: The ED-TOR rule was successfully validated using more recent data from a Japanese registry where CPR was performed according to the 2010 and 2015 guidelines. The ED-TOR rule was slightly superior to the BLS-TOR rule in Japanese EMS systems showing high specificity and PPV for predicting 1-month mortality.
Abstract 13548: Dicarbonyl Stress, Mitochondrial Impairments, and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension
Authors: Sasha Z Prisco, Lynn Hartweck, Megan Eklund, Thenappan Thenappan, Kurt W Prins
Journal: Circulation (2020)

Introduction: Right ventricular dysfunction (RVD) is the leading cause of mortality in pulmonary arterial hypertension (PAH), but the molecular mediators of RVD are incompletely understood. In PAH, RV glucose uptake is inversely proportional to RV function, which is a consequence of increased glycolytic flux due to mitochondrial dysfunction. Methylglyoxal (MG) is a highly reactive dicarbonyl that is generated during glycolysis. MG can deleteriously modulate protein function via post-translational modifications. MG is metabolized by two key enzymes: glyoxalase (Glo) 1 and 2. Finally, DJ-1 is a deglycase enzyme that reverses protein-glycation. The regulation of protein-glycation, the glyoxalase system, and DJ-1 in RVD due to PAH are unexplored. Methods: We analyzed protein-glycation, Glo-1/2, and DJ-1 expression in RV extracts from control, monocrotaline (MCT), and pulmonary artery banded (PAB) rats. The effects of protein-glycation on mitochondrial function in H9c2 cardiomyocytes were probed using Seahorse analysis. Finally, we examined the link between protein-glycation and RV function in PAH patients using hemoglobin-A1C as a surrogate measure of protein-glycation. Results: In MCT RVs, protein-glycation was increased (3.2±0.9-fold), Glo-1 (48±7%) was decreased, while Glo-2 (1.4±0.1-fold) and DJ-1 (1.5±0.4-fold) were increased. Conversely, in PAB rats, protein-glycation (1.4±0.3-fold) was not as drastically elevated. Moreover, Glo-1 (1.7±0.3-fold), Glo-2 (1.6±0.2-fold change), and DJ-1 (2.3±0.3-fold) levels were all increased. In H9c2 cardiomyocytes, MG treatment induced protein-glycation and impaired mitochondrial function. Finally, hemoglobin-A1C levels were inversely associated with RV contractility in PAH patients. Conclusions: Increased protein-glycation results in impaired mitochondrial function in vitro and is associated with more severe RV dysfunction in rodent and human PAH.
Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline
Authors: John D. Gordan, Erin B. Kennedy, Ghassan K. Abou-Alfa, Muhammad Shaalan Beg, Steven T. Brower, Terence P. Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, William P. Harris, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O. Kaseb, R. Kate Kelley, Jennifer J. Knox, Jeremy Kortmansky, Andrea Leaf, William M. Remak, Rachna T. Shroff, Davendra P.S. Sohal, Tamar H. Taddei, Neeta K. Venepalli, Andrea Wilson, Andrew X. Zhu, Michal G. Rose
Journal: Journal of Clinical Oncology (2020)

To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC).