tbuckley/cabot-search huggingface dataset:
Abstract 14685: Long-term Outcomes of Aortic Body Tumors: A Nationwide Study
Authors: Edgar Aranda-Michel, Olugbenga T Okusanya, Arman Kilic, Derek Serna-Gallegos, James A Brown, Valentino Bianco, Andreas Habertheuer, Ibrahim Sultan
Journal: Circulation (2020)

Introduction: Aortic body tumors are rare intrathoracic tumors. The majority of existing literature for aortic body tumors exists as case reports or a limited series. Our aim was to analyze a large national database, providing a contemporary view of this cancer. Methods: The national cancer database, which includes data from 1,500 cancer centers was queried to retrospectively review all aortic body tumors between 2004 and 2015. The cohort was divided into patients who underwent surgery versus those who were treated with chemotherapy or radiation. Cohorts were assigned a year range based on when they were diagnosed. Survival between these cohorts were compared using Kaplan-Meier survival estimates. Cox multivariable analysis was performed using baseline variables (age, year range, metastasis, surgery, radiation, and chemotherapy). Overall survival of the cohort was analyzed via Kaplan-Meier survival estimates. Results: A total of 87 patients who were diagnosed with an aortic body tumor were identified. The mean age was 51 ± 15.7 years and the majority of patients were female (51.7%). Most patients were treated at an academic/research center (62.7%) or a comprehensive community cancer program (25.4%). A significant portion of patients (19.5%) had metastatic disease on diagnosis. The treatment modalities utilized were surgery (54%), radiation (44.8%), and chemotherapy (20.7%). Long-term survival was 35.5% with a median survival of 8.25 years (Figure 1A) . Overall survival was significantly higher in the surgery cohort (p&lt;0.001) (Figure 1B) . On Cox multivariable analysis (Figure 1C) , surgery (HR 0.32, p=0.01) was associated with increased survival. An independent predictor of mortality was having a metastasis on diagnosis (HR 8.49, p=0.001). Conclusion: The overall prognosis of aortic body tumors is poor, with metastasis on presentation significantly increasing mortality. Surgery provides a substantial benefit to these patients; however, this may be a result of selection bias. Aggressive surveillance in predisposed populations may be warranted given the grave prognosis once metastasis occurs.
Abstract 14489: Physician Perspectives on the Diagnosis and Management of Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Michelle Padarath, Daniel Ngui, Justin Ezekowitz, Michelle Padarath, Alan Bell
Journal: Circulation (2020)

Introduction: Heart failure with preserved ejection fraction (HFpEF) carries high morbidity and mortality. Compared to heart failure with reduced ejection fraction (HFrEF), HFpEF is more difficult to diagnose and lacks in evidence-based treatments. We assessed the perceptions of CV specialists and primary care physicians (PCP) regarding HFpEF diagnosis and management. Methods: The online survey targeted 200 specialists and 200 (PCPs), offering a token honorarium. A total of 159 cardiologists (C), 59 internists (I), and 200 PCPs completed the survey. Results: All provinces were represented. The perceived prevalence of HFpEF vs HFrEF was similar across physician types (58% HFrEF, 42% HFpEF). Roughly 25% of PCPs did not differentiate between HF types. All physician types ranked symptom and mortality reduction as treatment priorities. The majority of specialists felt that HFpEF is best co-managed by primary and specialty care. One fifth of PCPs felt that HFpEF should be managed by primary care alone. Compared to specialists, PCPs were more likely to underestimate HFpEF mortality vs. HFrEF, less aware of gender differences, and less able to identify clinical findings of HFpEF vs. HFrEF. Fewer PCPs (33%) than specialists (50%) use natriuretic peptide (NP) levels for diagnosis, with PCPs expressing more uncertainty with NP utility. All physician types listed cost and limited availability as restrictions to use of NP testing. For evidence-based treatments in HF (ACEi/ARB, beta blockers, loop diuretics, mineralocorticoid receptor antagonists), &gt;50% of PCPs incorrectly identified all agents as effective for HFpEF, with &lt;10% stating that none improved outcomes. Cardiologists were more likely than internists to identify the lack of evidence-based treatments. Conclusions: This survey reveals substantial knowledge and treatment gaps in the diagnosis and management of HFpEF, specifically amongst PCPs. Given the prevalence of HFpEF in primary care, and its substantial morbidity and mortality, strategies are required to reduce these gaps. All physician types recognized the need for increased availability of NP testing for HFpEF diagnosis.
Abstract 13406: New Onset Atrial Fibrillation as a Predictor of Long Term All Cause Mortality: A Prospective Study
Authors: Paul M Thein, Adam J Brown, Sam Mirzaee, Abdul R Ihdayhid, Chen Li, James D Cameron, Arthur Nasis
Journal: Circulation (2018)

Introduction: New-onset atrial fibrillation with rapid ventricular rate(AFRVR) and sinus tachycardia(ST) commonly require medical emergency team(MET) response in a hospital setting, but the associa...
Abstract 16294: A Case of Paradoxical Coronary Embolism in a Patient With Undiagnosed Malignancy
Authors: Anh Do, Lindsey Aurora, MOHAMMAD ZAIDAN
Journal: Circulation (2020)

Introduction: Coronary embolism is a rare cause of acute myocardial infarction (AMI) in comparison with atherosclerotic plaque rupture. We present a case of an inferior ST elevation myocardial infarction caused by coronary embolism. The source was thought to be from the combination of deep vein thrombosis (DVT) and patent foramen ovale (PFO), accounting for a unique presentation and pathophysiology. Case: An 86-year-old female with a history of hypertension, non-small cell lung cancer status post resection with no residual disease, presented with a three-day history of epigastric discomfort, dyspnea on exertion and confusion. On presentation, she was afebrile with normal vital signs. Physical exam revealed epigastric pain on palpation. Initial labs were significant for high sensitivity troponin elevation to 9591 ng/L. ECG showed ST elevations in leads II, III, aVF. Coronary angiogram showed distal left anterior descending artery 71% stenosis and left posterior descending artery 99% stenosis. Given multiple distal locations concerning for coronary emboli, coronary angioplasty was done without stenting given no evidence of plaque rupture. After the angiogram, patient was found to have slurred speech and left sided facial droop. CT head showed multiple embolic infarcts. A transesophageal echocardiogram revealed a small PFO but no valvular vegetation/calcification or left atrial appendage thrombus. Lower extremity dopplers demonstrated lower extremity DVT. CT abdomen showed a pancreatic mass with hepatic metastasis, concerning for metastatic pancreatic adenocarcinoma. Patient was started on atorvastatin and aspirin only as AMI was due to a suspected embolic event. She received an IVC filter due to contraindication of anticoagulation in acute stroke and discharged to follow up with Oncology outpatient. Conclusions: In comparison to atherosclerotic plaque rupture, AMI as a result of an embolic coronary phenomena is rare. In fact, less than 1% of AMIs are caused by paradoxical embolism due to a PFO. There are many case reports about embolic AMI due to valvular vegetation or calcification. However, paradoxical coronary embolism due to PFO should be considered in patients with risk factors for a hypercoagulable state such as malignancy or DVT.
Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a <i>PDGFRA</i> Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan
Authors: David Proudman, Aaron Miller, Dave Nellesen, Aparna Gomes, Raymond Mankoski, Chelsea Norregaard, Erin Sullivan
Journal: JAMA Network Open (2020)

<h3>Importance</h3> With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (<i>PDGFRA</i>) exon 18 variant, including<i>PDGFRA</i>D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. <h3>Objective</h3> To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a<i>PDGFRA</i>exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. <h3>Design, Setting, and Participants</h3> For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased<i>PDGFRA</i>testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic<i>PDGFRA</i>exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. <h3>Exposures</h3> The model compared scenarios with and without avapritinib in a formulary. <h3>Main Outcomes and Measures</h3> Annual, total, and per member per month (PMPM) budget impact. <h3>Results</h3> In a hypothetical 1-million member plan, fewer than 0.1 new patients with a<i>PDGFRA</i>exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a<i>PDGFRA</i>exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. <h3>Conclusions and Relevance</h3> These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.
Gynaecologist is struck off for misconduct in his treatment of four patients
Authors: Clare Dyer
Journal: BMJ (2020)

A locum consultant in obstetrics and gynaecology who was accused of a catalogue of clinical failings has been struck off the UK medical register after he repeatedly expressed contempt for the proceedings and declined to attend when his former patients were testifying.

Malay Haldar, who qualified in India in 1987, was charged at a medical practitioners’ tribunal with misconduct in his treatment of four patients while working as a locum in Harlow in 2016 and in Birmingham in 2018.

He carried out a perineal reconstruction on a hysterectomy patient when she had explicitly refused it, explaining that she was a widow and not interested in a sex life. …
The Role of Bariatric Surgery in Prevention of Kidney Disease Progression in Moderately Obese Patients With Type 2 Diabetes
Authors: Marcus Fernando Kodama Pertille Ramos, Flavio Roberto Takeda
Journal: JAMA Surgery (2020)

To the Editor We read with great interest the article by Cohen et al1 that compared the best medical treatment with gastric bypass for the remission of microalbuminuria in early-stage chronic kidney disease in patients with type 2 diabetes and obesity.
Abstract 16915: Potential Role of Endothelial Cell WWOX in the Pulmonary Vascular Response to Hypoxia
Authors: Marta T Gomes, Jiwang Chen, Yang Bai, Haibin Li, Sunit Singla, Roberto F MacHado
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation and dysfunction of pulmonary artery smooth muscle and endothelial cells (PASMC, PAEC). The WWOX/ Wwox gene encodes a tumor suppressor WW domain-containing oxidoreductase, known as WWOX. WWOX has been linked to several protein networks, highlighting its functions in cell homeostasis, survival and proliferation. Loss of WWOX gene expression is observed in human cancer cells, as lung cancer. We hypothesize that during hypoxia, WWOX expression is modulated in PAECs, regulating cell proliferation and selecting apoptosis-resistant cells, thus causing vascular remodeling. Methods and Results: Endothelial cell specific Wwox knockout mice were developed by a conditional ablation of Wwox gene expression using the Cre -Lox site-specific recombination system. We crossed Wwox flox/flox mice with CDH5 Cre+ mice, generating Wwox floxed, CDH-Cre+ specific mice that are tamoxifen-inducible (EC- WWOX KO). EC-WWOX KO mice were treated daily with tamoxifen or vehicle for 5 days and exposed to 10% hypoxia. After four weeks of hypoxia exposure, EC-WWOX KO mice showed increased right ventricular systolic pressure (RVSP) (P=0.0003) and Fulton index (RV (LV+S)) ( P=0.049), when compared to controls, suggesting PH development. In vitro , PAECs exposure to 3% hypoxia for 6 hours showed an increase of WWOX mRNA (P=0.0154) and protein (P&lt;0.05) expression levels, decreased of cell proliferation detected by CyQUANT assay and PCNA protein expression (P=0.0024). These effects did not extend to cells exposed to 3% hypoxia for 24h. Immunoblots showed activation of apoptotic markers, such as cleaved caspase 3, PARP and Bax, suggesting that in hypoxia there is a potential controlled balance between increased WWOX expression, decreased cell proliferation and stimulation of apoptosis in these cells. Conclusion: Loss of EC WWOX expression plays a significant role in the development of PH in mice exposed to chronic hypoxia. We speculate that increased WWOX expression with acute hypoxia exposure could contribute to the selection of proliferative and pro-apoptotic PAECs, characteristic of PAH. Studies seeking to understand the mechanisms surrounding WWOX expression in PAECs are ongoing.
Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness
Authors: Amra Jujić, Peter M. Nilsson, Naeimeh Atabaki-Pasdar, Anna Dieden, Tiinamaija Tuomi, Paul W. Franks, Jens Juul Holst, Signe Sørensen Torekov, Susana Ravassa, Javier Díez, Margaretha Persson, Emma Ahlqvist, Olle Melander, Maria F. Gomez, Leif Groop, Martin Magnusson
Journal: Diabetes Care (2020)

While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortality, and it was suggested that GIP plays a role in pathogenesis of coronary artery disease. We investigated the associations between fasting and postchallenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by mean intima-media thickness in the common carotid artery (IMTmeanCCA) and maximal intima-media thickness in the carotid bifurcation (IMTmaxBulb).Participants at reexamination within the Malmö Diet and Cancer-Cardiovascular Cohort study (n = 3,734, mean age 72.5 years, 59.3% women, 10.8% subjects with diabetes, fasting GIP available for 3,342 subjects, fasting GLP-1 available for 3,299 subjects) underwent oral glucose tolerance testing and carotid ultrasound.In linear regression analyses, each 1-SD increment of fasting GIP was associated with increased (per mm) IMTmeanCCA (β = 0.010, P = 0.010) and IMTmaxBulb (β = 0.014; P = 0.040) in models adjusted for known risk factors and glucose metabolism. In contrast, each 1-SD increment of fasting GLP-1 was associated with decreased IMTmaxBulb (per mm, β = -0.016, P = 0.014). These associations remained significant when subjects with diabetes were excluded from analyses.In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMTmeanCCA, while GLP-1 is associated with decreased IMTmaxBulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.
Targeting PAK4 Inhibits Ras-Mediated Signaling and Multiple Oncogenic Pathways in High-Risk Rhabdomyosarcoma
Authors: Atreyi Dasgupta, Laura Sierra, Susan V. Tsang, Lyazat Kurenbekova, Tajhal Patel, Kimal Rajapakse, Ryan L. Shuck, Nino Rainusso, Yosef Landesman, Thaddeus Unger, Cristian Coarfa, Jason T. Yustein
Journal: Cancer Research (2020)

Abstract Rhabdomyosarcoma (RMS) is the most prevalent pediatric soft-tissue sarcoma. Multimodal treatment, including surgery and traditional chemotherapy with radiotherapy, has contributed to improvements in overall survival rates. However, patients with recurrent or metastatic disease have 5-year survival rates of less than 30%. One reason for the lack of therapeutic advancement is identification and targeting of critical signaling nodes. p21-activated kinases (PAK) are a family of serine/threonine kinases downstream of multiple critical tumorigenic receptor tyrosine kinase receptors and oncogenic regulators, including IGFR and RAS signaling, that significantly contribute to aggressive malignant phenotypes. Here, we report that RMS cell lines and tumors exhibit enhanced PAK4 expression levels and activity, which are further activated by growth factors involved in RMS development. Molecular perturbation of PAK4 in multiple RMS models in vitro and in vivo resulted in inhibition of RMS development and progression. Fusion-positive and -negative RMS models were sensitive to two PAK4 small-molecule inhibitors, PF-3758309 and KPT-9274, which elicited significant antitumor and antimetastatic potential in several primary and metastatic in vivo models, including a relapsed RMS patient-derived xenograft model. Transcriptomic analysis of PAK4-targeted tumors revealed inhibition of the RAS-GTPase, Hedgehog, and Notch pathways, along with evidence of activation of antitumor immune response signatures. This PAK4-targeting gene signature showed prognostic significance for patients with sarcoma. Overall, our results show for the first time that PAK4 is a novel and viable therapeutic target for the treatment of high-risk RMS. Significance: These data demonstrate a novel oncogenic role for PAK4 in rhabdomyosarcoma and show that targeting PAK4 activity is a promising viable therapeutic option for advanced rhabdomyosarcoma.
Prediction Models for COVID-19 Need Further Improvements
Authors: Hong-Qiu Gu, Junfeng Wang
Journal: JAMA Internal Medicine (2020)

Wenhua Liang, MD; Hengrui Liang, MD; Limin Ou, MD; Binfeng Chen, MD; Ailan Chen, MD; Caichen Li, MD; Yimin Li, MD; Weijie Guan, MD; Ling Sang, MD; Jiatao Lu, MD; Yuanda Xu, MD; Guoqiang Chen, MD; Haiyan Guo, MD; Jun Guo, MD; Zisheng Chen, MD; Yi Zhao, MD; Shiyue Li, MD; Nuofu Zhang, MD; Nanshan Zhong, MD; Jianxing He, MD; for the China Medical Treatment Expert Group for COVID-19
Abstract 276: The Effects of Peep and Blood Pressure on Cerebral Tissue Oxygen Saturation During Hemorrhage in Swine
Authors: Jeff R Gould, Joshua W Lampe, Lyra Clark, George Beck, Brian C Harvey, Karen L Moodie, Norman A Paradis
Journal: Circulation (2020)

Introduction: Positive end-expiratory pressure (PEEP) is used to increase oxygen delivery by preventing end-expiratory alveolar collapse. However, the associated increased intrathoracic pressure can lead to an increase in right atrial pressure, and a decrease in venous return and cardiac output. Near infrared spectroscopy (NIRS) can be used as a non-invasive tool to continuously monitor cerebral tissue oxygen saturation. In this pilot study, we examined the effects of PEEP on cerebral oxygen saturation during a controlled hemorrhage. Methods: Four female, domestic swine (~30 kg), were bled to 3 target levels of mean arterial pressure (MAP; 55, 45, and 35 mm Hg). At each MAP target, 3 levels of PEEP were applied using a mechanical ventilator (5, 10, and 15 cm H 2 O) for ~10 minutes each. Following the reinfusion of shed blood and a recovery period, these interventions were repeated. Measurements included invasive aortic pressure and cerebral oxygen saturation using a commercially available tissue oximeter. A total of 61 epochs were entered into the following regression model: cerebral oxygen saturation = MAP + PEEP + animal number. Each epoch contained data from the last ~2 minutes of each MAP target and PEEP level. Results: The regression model yielded a coefficient of 0.30 for MAP ( P &lt; 0.001) and -0.08 for PEEP ( P = 0.09) and overall, explained 94% of the variance in cerebral oxygenation (adjusted R 2 = 0.94, P &lt; 0.001). While MAP was a stronger predictor in the model, higher PEEP levels appear to result in lower levels of cerebral oxygenation (see figure). Conclusions: Cerebral tissue oxygen saturation declines with lower mean arterial pressures and increased levels of PEEP. NIRS to measure cerebral oxygen saturation may be a useful clinical tool to ensure adequate cerebral oxygenation in patients with hypotension related to hemorrhage, particularly in those patients that require greater than physiologic PEEP to maintain central oxygenation.
Deep learning for in vitro prediction of pharmaceutical formulations
Authors: Yilong Yang, Zhuyifan Ye, Yan Su, Qianqian Zhao, Xiaoshan Li, Defang Ouyang
Journal: Acta Pharmaceutica Sinica B (2018)

Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error methods of pharmaceutical scientists. This approach is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. The aim of the present research is to apply deep learning methods to predict pharmaceutical formulations. In this paper, two types of dosage forms were chosen as model systems. Evaluation criteria suitable for pharmaceutics were applied to assess the performance of the models. Moreover, an automatic dataset selection algorithm was developed for selecting the representative data as validation and test datasets. Six machine learning methods were compared with deep learning. Results showed that the accuracies of both two deep neural networks were above 80% and higher than other machine learning models; the latter showed good prediction of pharmaceutical formulations. In summary, deep learning employing an automatic data splitting algorithm and the evaluation criteria suitable for pharmaceutical formulation data was developed for the prediction of pharmaceutical formulations for the first time. The cross-disciplinary integration of pharmaceutics and artificial intelligence may shift the paradigm of pharmaceutical research from experience-dependent studies to data-driven methodologies.