tbuckley/cabot-search huggingface dataset:
Abstract 15095: CSHA Frailty Scale as a Predictor of Hospital Readmission After PCI
Authors: John Raynak, Michael Cowherd, Hannan Yang, Clay Sherrill, Joseph Rossi
Journal: Circulation (2020)

Introduction: The Canadian Study on Health and Aging (CSHA) Frailty Scale was included in the National Cardiovascular Data Registry’s (NCDR) CathPCI registry beginning April 2018. The value of this frailty assessment as an independent predictor of hospital readmission is unknown. Methods: A retrospective analysis was performed of patients who underwent PCI within the University of North Carolina Medical System between 04/2018 and 12/2018. Outcome data was obtained from our electronic medical record data repository and procedural data from the institutional CathPCI registry. The primary outcome was repeat hospital admission within 1 year of PCI. Significant covariates (p&lt;0.05) in the univariate analyses were considered for inclusion in the multivariate model. Multivariate logistic regression was then performed to determine if CSHA Frailty Scale was an independent predictor of hospital readmission. Results: 1,592 subjects were identified with 367 readmission events. Patients in the readmission cohort were older, had a higher frailty score, and had more comorbidities. Table 1 summarizes the comorbidities included in the logistic regression. CSHA Frailty Scale did not meet significance requirements (P&lt;.05) to be independently associated with readmission. Covariates that were significant independent predictors of readmission included age (OR 1.024, 95% CI 1.012-1.036); cerebrovascular disease (OR 1.688, 95% CI 1.234-2.308); dialysis (OR 2.983, 95% CI, 1.583-5.622); and CHF (OR 2.465, 95% CI, 1.851-3.282). Conclusions: The CSHA Frailty Scale was not independently associated with readmission in the setting of PCI in our health system. This particular assessment of frailty may not provide added value over traditional comorbidities in this patient population.
Activation of Receptor Tyrosine Kinases Mediates Acquired Resistance to MEK Inhibition in Malignant Peripheral Nerve Sheath Tumors
Authors: Jiawan Wang, Kai Pollard, Ana Calizo, Christine A. Pratilas
Journal: Cancer Research (2020)

Abstract Malignant peripheral nerve sheath tumors often arise in patients with neurofibromatosis type 1 and are among the most treatment-refractory types of sarcoma. Overall survival in patients with relapsed disease remains poor, and thus novel therapeutic approaches are needed. NF1 is essential for negative regulation of RAS activity and is altered in about 90% of malignant peripheral nerve sheath tumors (MPNST). A complex interplay of upstream signaling and parallel RAS-driven pathways characterizes NF1-driven tumorigenesis, and inhibiting more than one RAS effector pathway is therefore necessary. To devise potential combination therapeutic strategies, we identified actionable alterations in signaling that underlie adaptive and acquired resistance to MEK inhibitor (MEKi). Using a series of proteomic, biochemical, and genetic approaches in an in vitro model of MEKi resistance provided a rationale for combination therapies. HGF/MET signaling was elevated in the MEKi-resistant model. HGF overexpression conferred resistance to MEKi in parental cells. Depletion of HGF or MET restored sensitivity of MEKi-resistant cells to MEKi. Finally, a combination of MEK and MET inhibition demonstrated activity in models of MPNST and may therefore be effective in patients with MPNST harboring genetic alterations in NF1. Significance: This study demonstrates that MEKi plus MET inhibitor may delay or prevent a novel mechanism of acquired MEKi resistance, with clinical implications for MPNST patients harboring NF1 alterations.
Abstract 13735: Coronary Endothelial Dysfunction Plays Important Roles on Development of Acute Coronary Syndrome and Fatal Cardiovascular Events During Long-term Follow-up Over 10 Years
Authors: Tatsuaki Murakami, Kazuo Ohsato
Journal: Circulation (2020)

Introduction: Although coronary endothelial dysfunction is thought to affect coronary atherothrombogenic processes, there has been little practical evidence for the relationship between clinical evolution of fatal or non-fatal acute coronary syndrome (ACS) and coronary endothelial dysfunction. Hypothesis: We assessed hypothesis that coronary endothelial dysfunction has clinical impacts on development of ACS and fatal cardiovascular events. Methods: Coronary endothelial dysfunction was practically graded by the flow-mediated endothelium-dependent reactive changes in coronary artery diameter (CFMD) to infusion of adenosine triphosphate (ATP ; 50μg) into the normal left coronary artery using quantitative coronary arteriography in 150 patients with stable coronary artery disease. The enrolled patients were categorized into tertile groups according to the values of CFMD, and we prospectively followed-up major adverse clinical cardiac events including ACS and cardiovascular death. Results: For a mean follow-up period of 132 months (range; 120 to 144) with complete follow-up, the patients in the lower third with severe coronary endothelial dysfunction (Group-L) more frequently developed ACS than those in the middle third with mild coronary endothelial dysfunction (Group-M) plus those in the higher third without coronary endothelial dysfunction (Group-H) [Group-L versus Group-M plus Group-H: 15(30%) versus 5(10%) plus 0(0%), p&lt;0.001, by Kaplan-Meier analysis]. Majority of the patients who resulted in cardiovascular death belonged to Group-L, [6(12%) versus 1(2%) plus 0(0%), p=0.014]. Cox hazard proportional model analyses indicated that severe coronary endothelial dysfunction was the strong predictor for future ACS (hazard ratio=7.53, 95%confidential interval; 1.78-12.25, p&lt;0.001) and future cardiovascular death (hazard ratio=13.50, 95%confidential interval; 1.55-25.25, p=0.005). Conclusions: This is the novel and longest follow-up investigation that demonstrates coronary endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events and therefore the strategies based on status of coronary endothelial dysfunction are required to prevent major adverse ischemic cardiac events.
Abstract 14613: Preclinical Animal Model of Doxorubicin-induced Left Ventricular Dysfunction: Echocardiography and Pressure-volume Analysis
Authors: Petr Kala, Zuzana Honetschlagerova, Zuzana Huskova, Zdenka Vanourkova, Petra Škaroupková, Vojtech Melenovsky, Josef Veselka, Ludek Cervenka
Journal: Circulation (2020)

Introduction: There is a need to implement a preclinical model in addition to the well established ischemic or volume-overload models that would mimic the clinical course of patients with chemotherapy-induced heart failure. Doxorubicin is an anthracycline chemotherapeutic that is widely used in oncology, although its cardiotoxicity. Hypothesis: Doxorubicin-induced left ventricular dysfunction in rats fulfills echocardiography and hemodynamic characteristics of chemotherapy-induced heart failure. Methods: We randomly assigned Ren-2 transgenic hypertensive (TGR, n = 17) and normotensive rats (HanSD, n = 22), at the age of 8 weeks to doxorubicin (2.5 mg/kg in 0.5 ml of normal saline) or placebo in 6 intraperitoneal doses within two weeks (cumulative doxorubicin dose 15 mg/kg). Two weeks later, we performed echocardiography study, pressure-volume analysis (PV), and we weighed the organs. Results: In doxorubicin groups, there was a decrease in the left ventricle weight (1,22 vs. 0,85 g in TGR), while an increase in wall stress (22036 vs. 29754 μL*mmHg/g in TGR). Echocardiography suggested heart remodeling with a decrease in relative wall thickness - RWT (1.02 vs. 0.65 mm in TGR), and together with PV analysis showed a decrease in systolic parameters - left ventricle ejection fraction - LVEF (71.41 vs. 59.96 % in TGR), end-systolic pressure-volume ratio - ESPVR (0.82 vs. 0.45 mmHg/uL in TGR) and preload recruitable stroke work - PRSW (75.71 vs. 60.98 mmHg in TGR). Ventricular-arterial coupling (VAC = Ea/Ees, a measure of cardiac efficiency) was worsened in the doxorubicin groups (1.69 vs. 2.52 in TGR). For all the above p &lt; 0.05, in HanSD, the results were similar (all p &lt; 0.05). Conclusions: Our results suggest that systolic dysfunction and decrease of cardiac efficiency in this model could be caused by heart atrophy, and such an animal model could potentially be an easily reproducible model of chemotherapy-induced heart failure in preclinical cardio-oncology studies.
Abstract 16265: Acute Coronary Syndrome in Patients With Familial Hypercholesterolemia: Incidence, Predictors, and Outcomes
Authors: Babikir Kheiri, Sergio Fazio, Timothy F Simpson, Mohammed Osman, Sudarshan Balla, Michael D Shapiro
Journal: Circulation (2020)

Introduction: Individuals with Familial Hypercholesterolemia (FH) are at high risk for ASCVD events. However, little is known about the incidence, predictors, and outcomes of admissions for acute coronary syndromes (ACS) in this population. Objectives: To describe the in-hospital outcomes, readmission rates, and predictors of recurrent ACS in the FH population. Methods: Utilizing the National Readmission Databases from 10/2016 to 12/2017, we identified individuals with FH (ICD-10 E78.01) admitted with ACS. The primary outcome was in-hospital complications, which was compared using propensity-score matching (PSM 1:3). Multivariate logistic regression was performed to identify the predictors of 30-day readmissions. Results: There were a total of 1,697,513 ACS admissions during the study period (non-FH=1,969,979 and FH=534). Individuals admitted for ACS with FH were younger (median age 57 vs 69), had fewer comorbidities (hypertension, diabetes mellitus, and heart failure), were more likely to present with STEMI (32.8% vs 22.6%; p&lt;0.01) and more likely to undergo multi-vessels revascularization (CABG 12.7% vs 5.9%, p&lt;0.01; multivessel PCI 11.4% vs 7.6%, p&lt;0.01) than patients without FH. After PSM, FH patients more commonly experienced in-hospital VT arrest [11.8% vs 8.0%; p&lt;0.01] and required more frequent mechanical circulatory support [8.6% vs 3.3%; p&lt;0.01]) compared to those without FH. Although FH patients who survived the initial index admission (97.9%) had lower 30-day readmission rates than non-FH patients (9.3% vs 15.1%; p&lt;0.01), readmission was more frequently for cardiovascular disease (81.5% vs 46.5%; p&lt;0.01). Predictors of 30-day readmission were young age, male sex, diabetes, history of CAD, and smoking (p&lt;0.01). Conclusions: Individuals with FH admitted with ACS are younger, have fewer comorbidities, and more frequently present with STEMIs compared to those without FH. FH patients were more likely to suffer in-hospital cardiac complications. These results highlight the high-risk status of ACS and post-ACS care in FH patients.
Bone marrow mesenchymal stem cell‐conditioned medium facilitates fluid resolution via miR‐214‐activating epithelial sodium channels
Authors: Yan Ding, Yong Cui, Yapeng Hou, Hongguang Nie
Journal: MedComm (2020)

Acute lung injury (ALI) is featured with severe lung edema at the early exudative phase, resulting from the imbalance of alveolar fluid turnover and clearance. Mesenchymal stem cells (MSCs) belong to multipotent stem cells, which have shown potential therapeutic effects during ALI. Of note, MSC-conditioned medium (MSC-CM) improved alveolar fluid clearance (AFC) in vivo, whereas the involvement of miRNAs is seldom known. We thus aim to explore the roles of miR-214 in facilitating MSC-CM mediated fluid resolution of impaired AFC. In this study, AFC was increased significantly by intratracheally administrated MSC-CM in lipopolysaccharide-treated mice. MSC-CM augmented amiloride-sensitive currents in intact H441 monolayers, and increased α-epithelial sodium channel (α-ENaC) expression level in H441 and mouse alveolar type 2 epithelial cells. Meanwhile, MSC-CM increased the expression of miR-214, which may participate in regulating ENaC expression and function. Our results suggested that MSC-CM enhanced AFC in ALI mice in vivo through a novel mechanism, involving miR-214 regulation of ENaC.
Abstract 14486: Validation of the Intermountain Risk Score and Get With the Guidelines-Heart Failure Score in Predicting 30 Day and 1 Year Mortality
Authors: Erik K Engelsgjerd, Benjamin D Horne, Catherine P Benziger
Journal: Circulation (2020)

Background: The Intermountain Risk Score (IMRS) predicts mortality in heart failure (HF) patients utilizing common, inexpensive tests in conjunction with patient age and sex. IMRS has not been validated for Essentia Health (EH)’s patient population nor compared to various pre-existing scores in this population. Methods: Individuals were selected from the American Heart Association’s Get With The Guidelines®- HF (GWTG-HF) registry as patients to evaluate in a retrospective study. This patient population consists of consecutive inpatients age ≥18 admitted with a HF diagnosis at EH from 7/2017 through 6/2019. IMRS was derived using common HF laboratory measures (complete blood count and basic metabolic profile), age, and sex. EH is a large rural health care system in MN, WI, and ND. Results: A total of 703 individuals (mean age: 74.20, 44.38% female) were studied. The 30-day IMRS predicted 30 day mortality for both sexes (Females N=312: OR=1.19 (95% confidence interval: 1.08, 1.32) per +1, p&lt;0.001; Males N=391: OR=1.23 (1.12, 1.36) per +1, p&lt;0.001). The 1-year IMRS predicted 1-year mortality (Females: OR=1.14 (1.06, 1.23) per +1, p&lt;0.001; Males: OR=1.28 (1.18, 1.38) per +1, p&lt;0.001). Using sex-specific cut offs for IMRS, females had better 30-day risk stratification in moderate to high risk groups compared to low risk reference group (Mod-risk: OR=5.90 (1.35, 25.85), p=0.018; high-risk: OR=9.63 (2.12, 43.72), p=0.003) vs. men (Mod-risk: OR=1.52 (0.61, 3.79), p=0.37; high risk: OR=4.53 (1.92, 10.65), p&lt;0.001). The GWTG-HF risk score was significant for 30-day (OR=1.29 (1.16, 1.44) per +1, p&lt;0.001) and 1-year mortality (OR=1.23 (1.13, 1.35) per +1, p&lt;0.001) but was only calculated in 292 patients (41.5%). Conclusions: The Intermountain Risk Score is a useful predictor of 30-day and 1-year mortality for heart failure patients in a large rural healthcare system. The GWTG-HF risk score also predicts 30-day and 1-year mortality but is often not calculated due to not all variables being collected at each hospital visit (i.e. ejection fraction). The IMRS risk score uses simple variables that most patients have on admission and future study to evaluate cost-effectiveness as a prospective tool for initial risk estimation is warranted.
Telemedicine: don’t discount the value of in-person GP clinics to the medical trainee
Authors: Adam M J Peer
Journal: BMJ (2020)

The move towards telemedical consultation in light of the covid-19 pandemic is driving innovation in general practice at pace. Omitted from consideration in Stokel-Walker’s otherwise excellent piece,1 however, is the impact digitalised consultation will have on the development of medical trainees. …
Prevalence and frequency of menstrual cycle symptoms are associated with availability to train and compete: a study of 6812 exercising women recruited using the Strava exercise app
Authors: Georgie Bruinvels, Esther Goldsmith, Richard Blagrove, Andrew Simpkin, Nathan Lewis, Katie Morton, Ara Suppiah, John P Rogers, Kathryn E Ackerman, John Newell, Charles Pedlar
Journal: British Journal of Sports Medicine (2020)

Objectives The menstrual cycle can affect sports participation and exercise performance. There are very few data on specific menstrual cycle symptoms (symptoms during various phases of the cycle, not only during menstruation) experienced by exercising women. We aimed to characterise the most common symptoms, as well as the number and frequency of symptoms, and evaluate whether menstrual cycle symptoms are associated with sporting outcomes. Methods 6812 adult women of reproductive age (mean age: 38.3 (8.7) years) who were not using combined hormonal contraception were recruited via the Strava exercise app user database and completed a 39-part survey. Respondents were from seven geographical areas, and the questions were translated and localised to each region (Brazil, n=892; France, n=1355; Germany, n=839; Spain, n=834; UK and Ireland, n=1350; and USA, n=1542). The survey captured exercise behaviours, current menstrual status, presence and frequency of menstrual cycle symptoms, medication use for symptoms, perceived effects of the menstrual cycle on exercise and work behaviours, and history of hormonal contraception use. We propose a novel Menstrual Symptom index (MSi) based on the presence and frequency of 18 commonly reported symptoms (range 0–54, where 54 would correspond to all 18 symptoms each occurring very frequently). Results The most prevalent menstrual cycle symptoms were mood changes/anxiety (90.6%), tiredness/fatigue (86.2%), stomach cramps (84.2%) and breast pain/tenderness (83.1%). After controlling for body mass index, training volume and age, the MSi was associated with a greater likelihood of missing or changing training (OR=1.09 (CI 1.08 to 1.10); p≤0.05), missing a sporting event/competition (OR=1.07 (CI 1.06 to 1.08); p≤0.05), absenteeism from work/academia (OR=1.08 (CI 1.07 to 1.09); p≤0.05) and use of pain medication (OR=1.09 (CI 1.08 to 1.09); p≤0.05). Conclusion Menstrual cycle symptoms are very common in exercising women, and women report that these symptoms compromise their exercise participation and work capacity. The MSi needs to be formally validated (psychometrics); at present, it provides an easy way to quantify the frequency of menstrual cycle symptoms.
Abstract 14485: Landscape of Lipid Management Following an Acute Coronary Syndrome: Survey of Canadian Specialists
Authors: Michelle Padarath, Robert Welsh, Jean C Gregoire, Robert A Hegele, Michelle Padarath, Milan Gupta
Journal: Circulation (2020)

Background: Following an acute coronary syndrome (ACS), patients are at high risk for subsequent cardiovascular events. LDL-cholesterol lowering remains a pillar in secondary prevention following ACS. There remains significant variability in the application of LDL-lowering therapies in clinical practice. Methods/Results: A cross-sectional, online survey of 200 cardiovascular specialists across Canada. The survey consisted of 50 multiple-choice questions and free text entry. The survey was distributed to members of the Canadian Collaborative Research Network with $125 stipend offered. All participants stated that it was standard of practice to obtain a lipid panel during ACS admission, often within the first 24 hours (67.5%, n=135). 68.5% (n=137) stated their hospitals had standing orders for statin initiation at ACS presentation. In very high-risk patients (multiple cardiovascular events, polyvascular disease), the majority (75.5%; n=151) of participants indicated a target LDL-c of &lt;70 mg/dL. Further, 22% (n=44) would target lower LDL-c levels ranging from 19.3-65.7 mg/dL. Only 32.0% (n=64) of participants stated that &gt;70% of their ACS patients were at/below LDL-c targets of &lt;70 mg/dL. Patients presenting with ACS despite high intensity statin with LDL-c above target were most often (80.0%; n=160) started on ezetimibe. Post-discharge, the majority of respondents indicated they would assess the patient in clinic at 1-3 months, and &lt;50% would order a lipid profile prior to that visit. Respondents underestimated the prevalence of familial hypercholesterolemia (FH) in both the general population and in ACS patients. Experience with PCSK9 inhibitors varied with 42.0% (n=84) having prescribed to less than five patients. Forty percent of respondents expressed safety concern at achieved LDL-e levels below 40 mg/dL. Conclusion: There is significant variation in practice patterns involving LDL-lowering therapies in the post-ACS period, and probable under-recognition of FH in this very-high risk population. Further evidence to inform guidelines and clinical practice is urgently required.
Similar image search for histopathology: SMILY
Authors: Narayan Hegde, Jason D. Hipp, Yun Liu, Michael Emmert-Buck, Emily Reif, Daniel Smilkov, Michael Terry, Carrie J. Cai, Mahul B. Amin, Craig H. Mermel, Phil Q. Nelson, Lily H. Peng, Greg S. Corrado, Martin C. Stumpe
Journal: npj Digital Medicine (2019)

The increasing availability of large institutional and public histopathology image datasets is enabling the searching of these datasets for diagnosis, research, and education. Although these datasets typically have associated metadata such as diagnosis or clinical notes, even carefully curated datasets rarely contain annotations of the location of regions of interest on each image. As pathology images are extremely large (up to 100,000 pixels in each dimension), further laborious visual search of each image may be needed to find the feature of interest. In this paper, we introduce a deep-learning-based reverse image search tool for histopathology images: Similar Medical Images Like Yours (SMILY). We assessed SMILY's ability to retrieve search results in two ways: using pathologist-provided annotations, and via prospective studies where pathologists evaluated the quality of SMILY search results. As a negative control in the second evaluation, pathologists were blinded to whether search results were retrieved by SMILY or randomly. In both types of assessments, SMILY was able to retrieve search results with similar histologic features, organ site, and prostate cancer Gleason grade compared with the original query. SMILY may be a useful general-purpose tool in the pathologist's arsenal, to improve the efficiency of searching large archives of histopathology images, without the need to develop and implement specific tools for each application.