tbuckley/cabot-search huggingface dataset:
Abstract 71: Diagnosis of Cardiac Arrest by 911 Call Takers Improved with Education Without Changing Bystander CPR Rates
Authors: Dina Gozman, Michael R Sayre, Shawn Koser, David Witosky, James Davis, David Keseg
Journal: Circulation (2011)

Context: In most out-of-hospital cardiac arrest (OHCA) events, a telephone call to 911 is the first action by bystanders. Because the 911 call taker cannot see the victim, accurate diagnosis of cardiac arrest depends on the caller's verbal description. If cardiac arrest is not suspected, then no telephone CPR instructions will be given. Objective: We measured the impact of a change in the EMS call taker question sequence on the accuracy of diagnosis of cardiac arrest by 911 call takers. Methods: We retrospectively reviewed the Cardiac Arrest Registry to Enhance Survival (CARES) dataset for Jan 1, 2009 through Dec 31, 2010 from a single Midwestern US city, population 750,000 with a longstanding telephone CPR instruction program (APCO). We included OHCA cases of any age who were in arrest prior to the arrival of EMS and for whom resuscitation was attempted. In early 2010, 911 call takers were retrained to follow a revised telephone script that emphasized minimal questioning, assertive control of the callers, and provision of Hands-only telephone CPR instructions. In 2010, call recordings were reviewed regularly with feedback to the call taker. The main outcome measure was sensitivity of the 911 call taker in diagnosing cardiac arrest. We compared 2009 with 2010 using the χ 2 test and odds ratio (OR). Results: There were 509 OHCA cases in 2009 and 447 cases in 2010 (64/100,000 population). The mean age was 59 ± 18 years, and 60% were male. Only 26% of events were witnessed. Before the revision, 40% were identified by 911 dispatchers; and after the revised questioning sequence, 74% were identified (OR 4.3, CI95 3.2 - 5.6, p&lt;0.01). The mean time to question callers was 58 seconds before and 54 seconds after (p=NS). False positive rates changed little (676 before and 861 after). Bystander CPR was performed in 37.5% of events before and 37.4% of events after the training (p=NS). Conclusion: Emphasis on scripted assessment improved sensitivity without loss of specificity in identifying OHCAs. However, it did not translate to an increase in patients receiving bystander CPR.
Abstract 18730: Impact of Hospital Volume on Outcomes of Endovascular Stenting for Adult Aortic Coarctation: A 12-year US Experience
Authors: Parth Bhatt, Rajesh Sonani, Aashay Patel, Badal Thakkar, Achint Patel, Chirag Savani, Abhishek Dave, Samir Patel, Nilay Patel, Shilpkumar Arora, Ronak Bhimani, Sopan Lahewala, Sidakpal Panaich, Sunny Jhamnani, Vikas Singh, Abhishek Deshmukh, Nileshkumar J Patel, Apurva O Badheka
Journal: Circulation (2015)

Introduction: Use of transcatheter endovascular stenting has been increasing in the treatment of Coarctation of Aorta (CoA). The present study was undertaken on adults with CoA undergoing stent placement from the period of 2000 to 2011 to analyze the relationship of hospital volume to the outcomes of stenting in adults with CoA. Methods: We queried Healthcare Cost and Utilization Project (HCUP)’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011. Patients with CoA were identified using ICD-9-CM diagnosis code of 747.10. Patients≥18 years of age undergoing endovascular stenting were identified using ICD-9-CM procedure code of 39.90. Hospital volume was divided into two groups with ≥3 and &lt;3 procedures annually. The outcomes studied were procedure-related complications, length of stay (LOS), and cost in relation to the hospital volume. Complications were coded using specific patient safety indicator codes released by HCUP. Length of stay (≤1 and &gt;1 days) and cost (≤ $13,830 and &gt; $13,830) were divided at median and included in regression analysis. Results: No in-hospital death was reported in either group. Hospitals with ≥3 procedures annually had significantly lower incidence of complications (9.50% vs. 23.01%) compared to the hospitals with &lt;3 procedures annually (p=0.002). After multivariate regression analysis, compared to hospitals with &lt;3 procedures annually, the hospitals with ≥3 procedures annually had odds ratio (OR) of 0.40 (95% CI: 0.19-0.82, p=0.013) for having any complications, OR of 0.67 (95% CI: 0.39-1.17, p=0.15) for having LOS&gt;1 day, and OR of 0.72 (95% CI: 0.45-1.13, p=0.15) for having cost&gt;$13,830. Conclusion: Stenting in adults for aortic coarctation is remarkably safe and the outcomes of the procedure have improved in centers with annual hospital volume of ≥3 procedures, and there is also decreasing trend of procedure-related complications, shorter hospital stay, and lower costs compared to centers with annual volume &lt;3 procedures.
Comparison of PCR/FISH testing and next generation sequencing (NGS) in molecular diagnosis of advanced-stage lung adenocarcinoma.
Authors: Peter Whooley, Donald Guinee, Margaret T. Mandelson, Michal Hubka, Madhankumar Kuppusamy, Frank Chu, Steven H. Kirtland, Joseph Grant F Rosales
Journal: Journal of Clinical Oncology (2018)

262 Background: As the number of clinically actionable genetic markers for lung adenocarcinoma has increased, the need for accurate and timely identification of these markers has become paramount. In January 2018, our practice began systemically using NGS on all lung adenocarcinoma biopsy specimens. We compared NGS testing to our previous standard (PCR- and FISH-based assays) with regards to breadth of markers tested and time to diagnosis. Methods: We compared detection of mutations in EGFR, ALK, and ROS1 and time from resection or biopsy to test results in recently diagnosed patients from January-March 2018 with stage III/IV adenocarcinoma of the lung to similar patients diagnosed January-December 2016. Results: 63 patients were eligible for analysis: 17 patients in 2018 and 46 patients in 2016. Mean time to diagnosis was 13 days for EGFR, 16 days for ALK and 18 days for ROS1 in 2016, based on previous methods (PCR/FISH) compared to 27 days for EGFR, 26 days for ALK and 26 days for ROS1 in 2018 with NGS testing. Four of the 46 samples (8.6%) were found to have insufficient tissue using PCR/FISH, whereas 1 out of 17 (5.8%) samples were found to be insufficient with NGS testing. NGS testing returned up to 35 molecular markers, including those which might be targets for clinical trial therapy. Conclusions: The use of NGS testing increased the number of actionable molecular markers tested and appears to have resulted in an increase in the time taken to diagnose EGFR, ALK, and ROS1. The clinical significance of this time difference (i.e. time to treatment initiation) as well as ultimate cost of NGS compared to PCR/FISH remain to be determined. FIGURE 1: Time to diagnosis of molecular tests in lung adenocarcinoma stage III/IV using PCR/FISH from January through December 2016 and NGS from January through March 2018.[Table: see text]
Cartilaginous Fishes Provide Insights into the Origin, Diversification, and Sexually Dimorphic Expression of Vertebrate Estrogen Receptor Genes
Authors: Grant L Filowitz, Rajendhran Rajakumar, Katherine L O’Shaughnessy, Martin J Cohn
Journal: Molecular Biology and Evolution (2018)

Vertebrate estrogen receptors (ERs) perform numerous cell signaling and transcriptional regulatory functions. ERɑ (Esr1) and ERβ (Esr2) likely evolved from an ancestral receptor that duplicated and diverged at the protein and cis-regulatory levels, but the evolutionary history of ERs, including the timing of proposed duplications, remains unresolved. Here we report on identification of two distinct ERs in cartilaginous fishes and demonstrate their orthology to ERα and ERβ. Phylogenetic analyses place the ERα/ERβ duplication near the base of crown gnathostomes (jawed vertebrates). We find that ERα and ERβ from little skate (Leucoraja erinacea) and mammals share key subtype-specific residues, indicating conserved protein evolution. In contrast, jawless fishes have multiple non-orthologous Esr genes that arose by parallel duplications. Esr1 and Esr2 are expressed in subtype-specific and sexually dimorphic patterns in skate embryos, suggesting that ERs might have functioned in sexually dimorphic development before the divergence of cartilaginous and bony fishes.
Association Between High Levels of Hepatitis B Core Antibody and Seroclearance of Hepatitis B e Antigen in Individuals With Chronic Hepatitis B Virus Infection
Authors: Jessica Liu, Hui-Han Hu, Chia-Ling Chang, Chin-Lan Jen, Mei-Hsuan Lee, Sheng-Nan Lu, Li-Yu Wang, Quan Yuan, Ning-Shao Xia, Masaya Sugiyama, Nao Nishida, Masashi Mizokami, Chien-Jen Chen, Pei-Jer Chen, Hwai-I Yang
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 15616: Interleukin-21 Receptor Activation: A New Therapeutic Strategy for Peripheral Arterial Disease
Authors: Tao Wang, Alexis Cunningham, Surovi Hazarika, John R Lye, Warren J Leonard, Brian H Annex
Journal: Circulation (2014)

Background: Surgical hind-limb ischemia (HLI) in mice has evolved to become an invaluable preclinical model for peripheral arterial disease (PAD). Work from other groups and us, have shown differen...
Mutational mechanisms of amplifications revealed by analysis of clustered rearrangements in breast cancers
Authors: D. Głodzik, C. Purdie, I.H. Rye, P.T. Simpson, J. Staaf, P.N. Span, H.G. Russnes, S. Nik-Zainal
Journal: Annals of Oncology (2018)

BackgroundComplex clusters of rearrangements are a challenge in interpretation of cancer genomes. Some clusters of rearrangements demarcate clear amplifications of driver oncogenes but others are less well understood. A detailed analysis of rearrangements within these complex clusters could reveal new insights into selection and underlying mutational mechanisms.Patients and methodsHere, we systematically investigate rearrangements that are densely clustered in individual tumours in a cohort of 560 breast cancers. Applying an agnostic approach, we identify 21 hotspots where clustered rearrangements recur across cancers.ResultsSome hotspots coincide with known oncogene loci includingCCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, andMYC. Others contain cancer genes not typically associated with breast cancer:MCL1,PTP4A1, andMYB. Intriguingly, we identify clustered rearrangements that physically connect distant hotspots. In particular, we observe simultaneous amplification ofchr8:ZNF703/FGFR1 andchr11:CCND1 where deep analysis reveals that a chr8–chr11 translocation is likely to be an early, critical, initiating event.ConclusionsWe present an overview of complex rearrangements in breast cancer, highlighting a potential new way for detecting drivers and revealing novel mechanistic insights into the formation of two common amplicons.
Abstract 14824: Cardiomyopathy-associated RBM20-mutations Within the RS Domain Lead to Aberrant Splicing of TTN and RYR2 in Human Myocardium and to a Mislocalisation of the RBM20-protein
Authors: Anna Gaertner-Rommel, Baerbel Klauke, Wolfgang Linke, Deniz Kececioglu, Kai Thorsten Laser, Jan Gummert, Hendrik Milting
Journal: Circulation (2016)

Introduction: Mutations in human RBM20 have previously been shown to cause dilated cardiomyopathy. Within the nucleus RBM20 partially colocalises with other splice factors and binds RNA. Deep seque...
Immunonutrition
Authors: P. C Calder
Journal: BMJ (2003)

The potential to modulate the activity of the immune system by interventions with specific nutrients is termed immunonutrition. This concept may be applied to any situation in which an altered supply of nutrients is used to modify inflammatory or immune responses. However, immunonutrition has become associated most closely with attempts to improve the clinical course of critically ill and surgical patients, who will often require an exogenous supply of nutrients through the parenteral or enteral routes.  Major surgery is followed by a period of immunosuppression that increases the risk of morbidity and mortality due to infection. Improving immune function during this period may reduce complications due to infection. Critically ill patients are at greater risk of adverse outcomes than surgical patients. In these patients complex variable immune and inflammatory changes occur that are only now being well defined. A biphasic response with an early hyperinflammatory response followed by an excessive compensatory response associated with immunosuppression is seen in many such patients. Here, early treatment is aimed at decreasing the inflammatory response rather than enhancing it, to abrogate the hyperinflammation and prevent the compensatory immunosuppression.
National patient experience data and correlation with in-hospital adverse gynecologic cancer surgical outcomes.
Authors: Joseph Dottino, Weiguo He, Charlotte C. Sun, Hui Zhao, Karen H. Lu, Larissa Meyer
Journal: Journal of Clinical Oncology (2018)

21 Background: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) is a patient experience and quality of care measure that impacts hospital reimbursement. HCAHPS data is made available to the public through Centers for Medicare and Medicaid. Given the potential implications for healthcare decision-making, this study sought to determine the utility of hospital-level data from the HCAHPS survey as a predictor of in-hospital postoperative outcomes in gynecologic cancer patients by creating a link with the Nationwide Inpatient Sample (NIS) database, an inpatient care database developed for the Healthcare Cost and Utilization Project (HCUP). Methods: 2009-2011 HCAHPS survey data was used to assign hospitals into terciles by scores. The NIS database was used to identify admissions for cancer-specific surgeries for patients with ovarian, uterine, and cervical cancers. Outcomes included complications, mortality, and prolonged length of stay. Mixed effects models compared correlation of outcomes and HCAHPS scores, after adjustment for patient-level and hospital-level variables. Results: 17,509 linked encounters in 651 hospitals across the U.S. were identified, with 51% uterine, 40% ovarian, and 9% cervical cancer surgical admissions. In-hospital mortality was less likely in hospitals in the highest vs. lowest tercile of summary HCAHPS scores (odds ratio (OR) 0.54, 95% CI: 0.31-0.94). While higher scores were not associated with overall postoperative complications, by complication subcategory, admissions in top tercile hospitals were less likely to have surgical complications (OR 0.82, 95% CI 0.69-0.98). No differences were found in risk of medical or nursing-related complications, or prolonged hospitalization (p &gt; 0.05). Conclusions: For patients undergoing gynecologic oncology surgery, assessment of patient experience has limited correlation with in-hospital adverse surgical outcomes. Awareness of the limitations of HCAHPS survey data may better inform patients as consumers and highlights the importance for transparency of relevant quality measures.
Assessment of Barrett’s esophagus and dysplasia with ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography
Authors: Osman Ahsen, Kaicheng Liang, Hsiang-Chieh Lee, Michael Giacomelli, Zhao Wang, Benjamin Potsaid, Marisa Figueiredo, Qin Huang, Vijaysekhar Jayaraman, James Fujimoto, Hiroshi Mashimo
Journal: Endoscopy (2018)

Background This study aimed to evaluate the use of ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography (OCT) with micromotor catheters for the in vivo assessment of Barrett’s esophagus and dysplasia. Methods 74 OCT datasets with correlated biopsy/endoscopic mucosal resection histology (49 nondysplastic Barrett’s esophagus [NDBE], 25 neoplasia) were obtained from 14 patients with Barrett’s esophagus and a history of dysplasia and 30 with NDBE. The associations between irregular mucosal patterns on en face OCT, absence of mucosal layering, surface signal &gt; subsurface, and &gt; 5 atypical glands on cross-sectional OCT vs. histology and treatment history were assessed by three blinded readers. Results Atypical glands under irregular mucosal patterns occurred in 75 % of neoplasia (96 % of treatment-naïve neoplasia) vs. 30 % of NDBE datasets (43 % of short- and 18 % of long-segment NDBE). Mucosal layering was absent in 35 % of neoplasia and 50 % of NDBE datasets, and surface signal &gt; subsurface occurred in 29 % of neoplasia and 30 % of NDBE datasets. Conclusions Atypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.
Two abnormalities on diagnostic laparoscopy
Authors: Richard Keedwell, Dominic Byrne
Journal: BMJ (2018)

A 29 year old nulliparous woman presented with a two year history of cyclical pelvic pain and dyspareunia. She underwent a diagnostic laparoscopy to identify a cause for the pain, and this revealed two gynaecological abnormalities (fig 1). What are these abnormalities?



Fig. 1 
Pelvic structures at diagnostic laparoscopy for pelvic pain



The image shows a unicornuate uterus with a rudimentary uterine horn (fig 2, A) on the left side, and an incidental left ovarian cyst (fig 2, B).



Fig. 2 
(A) Rudimentary uterine horn. (B) Ovarian cyst (incidental finding)



Embryologically, the unicornuate uterus is thought to result from partial or complete failure of development of one of the paramesonephric (Mullerian) ducts.

The unicornuate uterus …
Decreasing time to treat using visual management tools.
Authors: Andrew Rothacker, Chad W. Cummings, Katherine Tullio, Alison Ibsen, Emily Elizabeth Monteleone, Rebecca Bottles
Journal: Journal of Clinical Oncology (2018)

277 Background: Time between positive cancer diagnosis and first treatment (TTT) has lengthened significantly nationwide over the last decade. Decreased TTT has been shown to positively impact patient outcomes such as anxiety and stress, and in some situations, overall survival (OS). As such, TTT (measured in median days) is a major initiative for disease programs at our large academic medical center. Impacting TTT is challenging given the usual sources of data, which are retrospective. Further, engaging the teams around the data was difficult. The need to illustrate patient delays in real-time was identified. Methods: A patient database was created, along with a dashboard, using a visual software package to track patient activity. Information is extracted from the database into a dashboard, including the patient’s appointments, treatments, and barriers to care. The dashboard was constructed with graphics of historical TTT by month, TTT distribution by treatment type, TTT by provider, and a graphic of the most common barriers to treatment. Additionally, the dashboard identified patients who were not scheduled for treatment, and were represented by a symbol on an x/y-axis graph. The x-axis represents the unique patient, while the y-access represents the days from diagnosis, with the symbol incrementing each day the treatment is not scheduled. Results: The dashboard is used weekly to huddle with clinical and non-clinical teams. Patients with no scheduled treatment are easily identifiable on the dashboard, with a focus on minimizing all patient’s TTT. Patients with extended schedule are actively engaged to reschedule and reduce their TTT. The breast cancer program began using the dashboard in July 2017. The surgical TTT was 30 days (n = 34). Post-implementation of the dashboard and multi-disciplinary huddles, it was found in April 2018 the TTT was 26 days (n = 36). Conclusions: Combining real-time data with simple data visualization tools allows teams to identify barriers to care easily. The visual tools identify outliers and allow teams to communicate on scheduling challenges of each patient. In conjunction with the multi-disciplinary huddles, the dashboard allows teams to track progress of each patient to ensure timely scheduling and coordination.
Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study
Authors: Robyn E Wootton, Rebecca B Lawn, Louise A C Millard, Neil M Davies, Amy E Taylor, Marcus R Munafò, Nicholas J Timpson, Oliver S P Davis, George Davey Smith, Claire M A Haworth
Journal: BMJ (2018)

Abstract Objectives To investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and cardiometabolic health is causal. Design Two sample, bidirectional mendelian randomisation study. Setting Genetic data taken from various cohorts comprised of the general population (mostly individuals of European ancestry, plus a small proportion of other ancestries); follow-up analysis included individuals from the United Kingdom. Participants Summary data were used from previous genome wide association studies (number of participants ranging from 83 198 to 339 224), which investigated traits related to cardiovascular or metabolic health, had the largest sample sizes, and consisted of the most similar populations while minimising sample overlap. A follow-up analysis included 337 112 individuals from the UK Biobank (54% female (n=181 363), mean age 56.87 years (standard deviation 8.00) at recruitment). Main outcome measures Subjective wellbeing and 11 measures of cardiometabolic health (coronary artery disease; myocardial infarction; total, high density lipoprotein, and low density lipoprotein cholesterol; diastolic and systolic blood pressure; body fat; waist to hip ratio; waist circumference; and body mass index). Results Evidence of a causal effect of body mass index on subjective wellbeing was seen; each 1 kg/m 2 increase in body mass index caused a −0.045 (95% confidence interval −0.084 to −0.006, P=0.02) standard deviation reduction in subjective wellbeing. Follow-up analysis of this association in an independent sample from the UK Biobank provided strong evidence of an effect of body mass index on satisfaction with health (β=−0.035 unit decrease in health satisfaction (95% confidence interval −0.043 to −0.027) per standard deviation increase in body mass index, P&lt;0.001). No clear evidence of a causal effect was seen between subjective wellbeing and the other cardiometabolic health measures, in either direction. Conclusions These results suggest that a higher body mass index is associated with a lower subjective wellbeing. A follow-up analysis confirmed this finding, suggesting that the effect in middle aged people could be driven by satisfaction with health. Body mass index is a modifiable determinant, and therefore, this study provides further motivation to tackle the obesity epidemic because of the knock-on effects of higher body mass index on subjective wellbeing.
KDM4B-regulated unfolded protein response as a therapeutic vulnerability in <i>PTEN</i>-deficient breast cancer
Authors: Wenyu Wang, Gokce Oguz, Puay Leng Lee, Yi Bao, Panpan Wang, Mikkel Green Terp, Henrik J. Ditzel, Qiang Yu
Journal: The Journal of Experimental Medicine (2018)

PTEN deficiency in breast cancer leads to resistance to PI3K–AKT inhibitor treatment despite aberrant activation of this signaling pathway. Here, we report that genetic depletion or small molecule inhibition of KDM4B histone demethylase activates the unfolded protein response (UPR) pathway and results in preferential apoptosis in PTEN-deficient triple-negative breast cancers (TNBCs). Intriguingly, this function of KDM4B on UPR requires its demethylase activity but is independent of its canonical role in histone modification, and acts through its cytoplasmic interaction with eIF2α, a crucial component of UPR signaling, resulting in reduced phosphorylation of this component. Targeting KDM4B in combination with PI3K inhibition induces further activation of UPR, leading to robust synergy in apoptosis. These findings identify KDM4B as a therapeutic vulnerability in PTEN-deficient TNBC that otherwise would be resistant to PI3K inhibition.