tbuckley/cabot-search huggingface dataset:
42O Biomarker analysis from KAITLIN, a randomised phase III study of adjuvant trastuzumab emtansine (TDM-1; K) plus pertuzumab (P) versus trastuzumab (H) plus taxane (T) plus P after anthracyclines (AC) for high-risk HER2-positive early breast cancer (EBC)
Authors: O. Metzger, C. Lambertini, I.E. Krop, G. Lewis Phillips, C.M. Perou, F. Symmans, I. Melero, N. Harbeck, E.P. Winer, S-A. Im, C.H. Barrios, H. Bonnefoi, J.R. Gralow, P.A. Ellis, L. Gianni, M. Toi, S.M. Swain, T. Boulet, C. Song, S. de Haas
Journal: Annals of Oncology (2021)
Abstract 16414: Pathologic Description of the Association of Bronchopulmonary Dysplasia and Left-to-right Shunts
Authors: Henry Schmidt, Alyssa M Vermeulen, Girish Sharma, Hoang Nguyen
Journal: Circulation (2020)

Introduction: Intracardiac left-to-right shunts, like atrial septal defect (ASD) and patent ductus arteriosus (PDA) have been shown to contribute to pulmonary hypertension in patients with bronchopulmonary dysplasia (BPD). There is no known comparison of heart and lung pathology in this population. The goal of our study was to characterize lung and heart pathology in patients with BPD and intracardiac shunts as well as correlate post-mortem changes with BPD classification. Hypothesis: Infants with greater degree of intracardiac shunt or persistent shunt will have more severe BPD classification and more severe heart and lung pathology. Methods: A retrospective cohort between 2011 and 2017 of 491 patients with BPD and prematurity were reviewed. There were 16 deceased patients, and 8 with autopsy who were included in the study. Outcomes measured were presence of shunt, pre and perinatal risk factors associated with BPD, degree of respiratory, inotropic and pulmonary vasodilator support, severity of BPD and heart and lung pathology on autopsy. Results: There was a low incidence of chorioamnionitis (12.5%), sepsis (12.5%), or maternal smoking (12.5%). Three patients had fetal growth restriction (37.5%). Seven patients (87.5%) received prenatal steroids and surfactant. At time of autopsy, 3 had an ASD, 3 had no shunt, 2 had shunts that had been closed; 1 patient had an ASD device closure, 3 had a PDA ligation and 1had PDA device closure. All patients had either a PDA or ASD at some point in infancy by echocardiogram. Six of the 8 patients had severe BPD and 2 had moderate BPD. All but one patient had abnormal right heart pathology(right atrial enlargement, right ventricular hypertrophy, and enlarged pulmonary artery) and abnormal lung pathology. One patient without right heart pathology had normal lung pathology, an isolated PDA that was ligated and moderate BPD. Patients who had moderate to large ASD (&gt; 6 mm) demonstrated worse lung and heart pathology. Conclusions: Infants with larger intracardiac shunts, were found to have more severe lung and heart disease. This data may suggest earlier closure of moderate to large intracardiac shunts, particularly ASD in this population may be beneficial to worsening cardiac and pulmonary disease in this population.
Abstract 16687: The Use of Evidence by Stakeholders in Developing Nutrition Policy: Preventing Heart Disease and Stroke Through Reducing Sodium and Trans Fat Intake
Authors: Lesley James
Journal: Circulation (2020)

Introduction: High intake of sodium and trans fat are leading risk factors for heart disease and stroke. Scientific bodies including AHA have recommend reductions in their intake to prevent poor health outcomes. The government of Canada developed sodium and trans fat reduction strategies in collaboration with a wide range of stakeholders. Both strategies resulted in a voluntary approach despite the efforts of the cardiovascular and public health communities to secure regulation. Methods: A mixed method research study was undertaken to assess and analyze the policy making process around trans fat and sodium reduction. A novel content analysis was conducted on the Government of Canada lobby registry which quantified the lobbying efforts of various stakeholders. Next, key informant interviews were conducted with stakeholders involved in the policy processes to better understand contextual dynamics that led to the adoption of voluntary measures. Results: The lobby registry assessment found that the during the policy negotiations, the food industry was significantly more likely to meet with government officials than public health and clinical associations. The food industry also met with higher profile and powerful government officials than health organizations which may have facilitated a greater influence. Based on thematic analysis, the use of scientific evidence and values played a key role in the decision-making processes and the overall effectiveness of the voluntary policy measures. Data and evidence were misused by stakeholders, and this could have contributed to a general confusion about the need for public health policy and regulation. Conclusions: The policy processes around trans fat and sodium reduction were influenced by competing commercial interests which overtook the objectives of public health and clinical associations. As health groups aim to create healthier food environments around the world, it is important to understand and be prepared for the various interpretations of evidence, policy objections and counter tactics of powerful multi-national food companies. Efforts should also be made to strategically align stakeholders who influence public health policy including media, the general public and health professionals.
Abstract 16486: Consistent Cost-effectiveness of Icosapent Ethyl Across Patient Profiles From REDUCE-IT
Authors: Zugui Zhang, Deepak L Bhatt, Sarahfaye Dolman, William E Boden, Philippe G Steg, Michael Miller, Eliot A Brinton, Jordan B King, Adam P Bress, Terry A Jacobson, Jean-Claude Tardif, Christie M Ballantyne, Paul Kolm, William S Weintraub
Journal: Circulation (2020)

Background: The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) showed that patients with elevated baseline triglycerides (TG) and well-controlled LDL-C levels on statins had a 30% lower risk of total cardiovascular events with 4g of icosapent ethyl (IPE) daily compared to standard care (SC) during a median 4.9 year follow-up. The purpose of this study was to conduct subgroup analyses of lifetime cost-effectiveness (CE) of IPE compared to SC alone. Methods: Applying treatment effects from REDUCE-IT, health care costs from the National Inpatient Sample (NIS), and net costs for IPE of $4.16 a day, we conducted a combination CE analysis utilizing patient level in-trial cost and clinical outcomes with long-term costs, events, and life expectancy derived from Markov simulation models. The model projected lifetime health care costs, cardiovascular events, survival, and quality-adjusted life-years (QALYs) for IPE vs. SC from a payer perspective among overall trial-eligible patients and in key subgroups. Results: The lifetime mean costs for IPE and SC were $196,080 and $197,064, and the lifetime QALYs for IPE and SC were 10.61 and 10.35, respectively (Table 1). IPE was a dominant strategy over the lifetime in 69.7% of simulations with the probability of CE at the nominal $50,000, $100,000, and $150,000 thresholds being replicated in 87.9%, 98.6%, and 99.9% of simulations, respectively. In the subgroups of age &lt;65 years, male sex, subjects with or without diabetes, secondary prevention cohort, TG levels ≥200 or ≥150 mg/dL, and baseline LDL≥70 mg/dL, IPE was a dominant strategy over the lifetime. In women or the primary prevention cohort, IPE was cost-effective with an ICER of $16,660 or $21,890 per QALY gained, respectively. Conclusions: In all subgroups, IPE at a cost of $4.16/day was shown to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY and was a dominant treatment strategy in most subgroups.
Contamination of Retail Meat Samples with Multidrug-Resistant Organisms in Relation to Organic and Conventional Production and Processing: A Cross-Sectional Analysis of Data from the United States National Antimicrobial Resistance Monitoring System, 2012–2017
Authors: Gabriel K. Innes, Keeve E. Nachman, Alison G. Abraham, Joan A. Casey, Andrew N. Patton, Lance B. Price, Sara Y. Tartof, Meghan F. Davis
Journal: Environmental Health Perspectives (2021)

BACKGROUND: During food animal production, animals are exposed to, colonized by, and sometimes infected with bacteria that may contaminate animal products with susceptible and multidrug-resistant organisms (MDRO).The United States' Organic Foods Production Act resulted in decreased antibiotic use in some animal production operations.Some studies have reported that decreased antibiotic use is associated with reduced MDRO on meat.OBJECTIVES: The aim of this study was to investigate associations of meat production and processing methods with MDRO and overall bacterial contamination of retail meats.METHODS: Bacterial contamination data from 2012 to 2017 for chicken breast, ground beef, ground turkey, and pork chops were downloaded from the National Antimicrobial Resistance Monitoring System.Poisson regression models with robust variance were used to estimate associations with MDRO contamination and any contamination (adjusted for year and meat type) overall, and according to bacteria genus (Salmonella, Campylobacter, Enterococcus, Escherichia coli) and meat type.RESULTS: A total of 39,349 retail meat samples were linked to 216 conventional, 123 split (conventional and organic), and three organic processing facilities.MDRO contamination was similar in conventionally produced meats processed at split vs. conventional facilities but was significantly lower in organically produced meats processed at split facilities ½adjusted prevalance ratio ðaPRÞ = 0:43; 95% CI: 0.30, 0.63].Meat processed by split vs. conventional processors had higher or similar MDRO contamination for all tested bacterial genera except Campylobacter (aPR = 0:29; 95% CI: 0.13, 0.64).The prevalence of any contamination was lower in samples processed at split vs. conventional facilities for aggregated samples (aPR = 0:70; 95% CI: 0.68, 0.73) and all meat types and bacterial genera.DISCUSSION: Organically produced and processed retail meat samples had a significantly lower prevalence of MDRO than conventionally produced and processed samples had, whereas meat from split processors had a lower prevalence of any contamination than samples from conventional processors had.Additional studies are needed to confirm findings and clarify specific production and processing practices that might explain them.
<i>Helicobacter pylori</i> PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity
Authors: Miguel S. Marques, Ana C. Costa, Hugo Osório, Marta L. Pinto, Sandra Relvas, Mário Dinis-Ribeiro, Fátima Carneiro, Marina Leite, Ceu Figueiredo
Journal: Gut Microbes (2021)

Helicobacter pylori infects approximately half of the world's population and is the strongest risk factor for peptic ulcer disease and gastric cancer, representing a major global health concern. H. pylori persistently colonizes the gastric epithelium, where it subverts the highly organized structures that maintain epithelial integrity. Here, a unique strategy used by H. pylori to disrupt the gastric epithelial junctional adhesion molecule-A (JAM-A) is disclosed, using various experimental models that include gastric cell lines, primary human gastric cells, and biopsy specimens of infected and non-infected individuals. H. pylori preferentially cleaves the cytoplasmic domain of JAM-A at Alanine 285. Cells stably transfected with full-length JAM-A or JAM-A lacking the cleaved sequence are used in a range of functional assays, which demonstrate that the H. pylori cleaved region is critical to the maintenance of the epithelial barrier and of cell-cell adhesion. Notably, by combining chromatography techniques and mass spectrometry, PqqE (HP1012) is purified and identified as the H. pylori virulence factor that cleaves JAM-A, uncovering a previously unreported function for this bacterial protease. These findings propose a novel mechanism for H. pylori to disrupt epithelial integrity and functions, breaking new ground in the understanding of the pathogenesis of this highly prevalent and clinically relevant infection.
Urgent call to prevent late stage presentation of head and neck cancer
Authors: Euan D Mackinnon, Sangeetha Sornalingam, Max Cooper
Journal: BMJ (2021)

We agree with Tang and colleagues that safer indoor environments are needed as covid-19 becomes something we may have to live with.1

The pandemic has placed significant strain on primary care medical and dental services. Consultations have primarily moved to a telemedicine service with limited face-to-face contact. GPs were initially advised not to examine the oral cavity unless deemed essential.2 In the UK dental sector, over 14 million appointments were missed …
Abstract P069: White Cell Gene Expression Related To Immune Function And Cumulative Blood Pressure During Young Adulthood And Middle Age: Coronary Artery Risk Development In Young Adults (CARDIA)
Authors: Myron D Gross, Bharat Thyagarajan, Sithara Vivek, David R Jacobs
Journal: Circulation (2021)

Introduction: High blood pressure (BP) is a global public health problem that is strongly associated with many aspects of cardiovascular disease. Approximately 90% of hypertension cases have unknown cause. Studies of white blood cell gene expression may help to clarify the pathobiology. Methods: Gene expression (25 genes) was assayed in CARDIA at the Year 25 Exam (N=3,074 black and white men and women in 4 US cities, examined in 2010-2011, age 42-56 years). Whole blood was collected in PAXgene Blood RNA tubes; mRNA was isolated using the PAXgene Blood RNA kit (Qiagen Inc., Germantown, MD). The nCounter analysis system (Nanostring Inc., Seattle, WA) was used to measure expression of 25 genes related to inflammation and oxidative stress. Gene expression levels were logarithmically (base 2) transformed to approximate a normal distribution, so 1 unit higher represents doubling of the expression. Average cumulative sitting rest BP exposure was calculated (N=2,823) as the time weighted average across ≥5 BP measurements among 9 CARDIA exams with ≥1 measurement in each of Set 1 Years 0, 2, 5, 7; Set 2 Years 10, 15; and Set 3 Years 20, 25, 30. We added 10 mmHg to the systolic BP and 5 mmHg to the diastolic BP at visits in which antihypertensive medications were used. Linear regression estimated associations between dependent variables cumulative systolic and diastolic BP and each of the 25 gene expression levels, adjusting for age, race, sex, clinic, and year 25 body mass index. Hypertension at year 25 was defined as BP &gt;140/90 mmHg or taking antihypertensive medications and pre-hypertension at year 25 was defined as BP between 121-139/81-90 mmHg, not taking antihypertensive medications. Unconditional logistic regression models were used to estimate the cross sectional association between hypertension and gene expression after adjusting for the covariates mentioned above. Results: The mean ± standard deviation for cumulative systolic BP was 113±11 mm Hg and for cumulative diastolic BP was 72±8 mmHg. NADH Dehydrogenase [Ubiquinone] 1 Beta Subcomplex Subunit 3 ( NDUFB3) , a mitochondrial gene involved in the electron transport chain was significantly associated with both cumulative systolic (β=1.549; p&lt;0.0001) and diastolic BP measures (β=1.281 mmHg/1 log 2 unit of expression; p&lt;0.0001), even after Bonferroni correction. Other genes had weaker signals. Consistent with these observations, hypertension (n=898) at year 25 (OR: 1.737; p&lt;0.001) and pre-hypertension (n=1,127) at year 25 (OR:1.288; p=0.005) were also associated with increased NDUFB3 expression. Conclusions: Expression of the NDUFB3 gene, an element of oxidative stress, was associated with BP assessed throughout young adult and middle age and with concurrent hypertension.
Comment on Lee et al. Multicenter, Head-to-Head, Real-World Validation Study of Seven Automated Artificial Intelligence Diabetic Retinopathy Screening Systems. Diabetes Care 2021;44:1168–1175
Authors: Peter Soliz
Journal: Diabetes Care (2020)

Allow me to make these observations on the article by Lee et al. (1) in this issue of Diabetes Care . The topic of artificial intelligence (AI) techniques, deep learning in particular, for interpretation of medical images for use in clinical environments is timely. We congratulate the authors for their contribution to a highly relevant topic.

The strengths of the article are many. For example, the results show that some implementations of AI for diabetic retinopathy (DR) screening are highly effective and can have a significant impact on increasing access to DR screening in a cost-effective manner.

There are five notable observations that I wish to make. First, the referral criteria were …
Paradigm Shifts in the Management of Diabetes in Pregnancy: The Importance of Type 2 Diabetes and Early Hyperglycemia in Pregnancy
Authors: David Simmons
Journal: Diabetes Care (2020)

For over 50 years, the diagnosis of gestational diabetes mellitus (GDM) has been based upon an oral glucose tolerance test at 24-28 weeks' gestation. This is the time during pregnancy when insulin resistance is increasing and hyperglycemia develops among those with insufficient insulin secretory capacity to maintain euglycemia. The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the two major randomized controlled trials of treating GDM are based upon recruitment of women at this time during pregnancy. Meanwhile, the increasing prevalence of type 2 diabetes in pregnancy, with its significant risk of adverse pregnancy outcomes, has led to a need to identify undiagnosed diabetes as near to conception as possible. Screening for undiagnosed diabetes early in pregnancy also identifies women with hyperglycemia less than overt diabetes, yet at increased risk of adverse pregnancy outcomes. Such women are more insulin resistant-with higher blood pressure, triglycerides, perinatal mortality, and neonatal hypoglycemia with a greater need for insulin treatment-than those with GDM diagnosed at 24-28 weeks' gestation. Currently, there is uncertainty over how to diagnose GDM early in pregnancy and the benefits and harms from using the current management regimen. Randomized controlled trials testing the criteria for, and treatment of, GDM early in pregnancy are urgently needed to address this existing equipoise. In the meantime, the importance of early or "prevalent GDM" (i.e., mild hyperglycemia present from early [before] pregnancy) warrants interim criteria and thresholds for medication, which may differ from those in use for GDM diagnosed at 24-28 weeks' gestation.
Dysphagia: revisiting investigations
Authors: Yong Sul Kim, Ross Hansen, May YW Wong
Journal: Gut (2021)

A 63-year-old man with a 3-month history of progressively worsening dysphagia to solids and liquids and a weight loss of 20 kg was referred following high-resolution manometry (HRM). He was only able to tolerate moderately thick liquids. There was no history of abdominal pain, chest pain, heartburn or night sweats. He had no medical history of GI reflux or chronic alcohol abuse however he was an ex-smoker with a 40-pack year history. He had a brother with a diagnosis of pancreatic cancer at the age of 60. On examination, his vital signs were stable, and his abdomen was soft and flat without tenderness.

Laboratory tests revealed a normal haemoglobin, white cell count and ferritin. The …
Abstract 14767: Thrombolysis of Stroke Mimics via Telestroke
Authors: Ravyn Howell, Randheer S Yadav, Sushil Lakhani, Sharon Heaton, Karen L Wiles, Vivien H Lee
Journal: Circulation (2020)

Introduction: Telestroke allows stroke expertise for thrombolysis decision making remotely using high-quality bidirectional audiovisual technology. Hypothesis: Intravenous tissue plasminogen activator (IVtPA) is administered via telestroke network to a proportion of patients without a stroke diagnosis (i.e. stroke mimic) Methods: Our academic comprehensive stroke program telestroke program includes 26 spoke Emergency rooms (ERs) through which IVtPA is administered throughout central Ohio. From July 1, 2016 to Sept 30, 2017, nearly all patients who received IVtPA at the outside hospital telestroke ERs were transferred to our institution for post-IVtPA care. Data was collected on final diagnosis, demographics, National Institutes of Health Stroke Scale (NIHSS), door to needle (DTN) time, and outcomes. Results: Among 270 acute ischemic stroke patients who received IVtPA via telestroke, we identified 64 (23.7%) with a stroke mimic diagnosis. Stroke mimics were younger (mean age 56.4 vs 68.2, p &lt;0.0001), more likely female (60.9% vs 45.6%, p 0.03), and had higher DTN times (85.3 vs 69.9 minutes, p 0.0008). The increase in DTN was due to longer time to recommend by the telestroke neurologist for stroke mimic (65.0 vs 53.2 minutes, p 0.0034). The stroke mimic diagnosis included Migraine 26 (40.6%), Factitious disorder 12 (18.8%), Encephalopathy 7 (10.9%), and Unmasking 6 (9.4%). The stroke mimics did not differ from each other based upon initial NIHSS, DTN, or sex. Compared to the other stroke mimics, Migraine and Factitious disorder patients were younger (51.2 vs 63.9 years, p &lt;0.0006), more likely to have a personal history of migraines (42.1% vs 0%, p &lt; 0.0001), and more likely to have functional exam findings (42.1% vs 3.8%, p 0.0007). There were no hemorrhagic complications in the stroke mimic patients. Among all stroke mimics, 26 (40.6%) had a history of similar prior episodes and 10 (15.6%) would have future recurrence of another similar episode, with 2 patients receiving IVtPA again in the future (1 Migraine and 1 Factitious disorder). Conclusions: In a tertiary academic telestroke network, nearly one-quarter of patients receive IVtPA for a non-stroke diagnosis, with migraine and factitious disorder being the most commonly seen.